Index

A structures and active sites of, other therapies/future directions Aβ, 627–628 114–121 of, 635–637 NGF’s regulation of, 629–630 synthesis of, 16, 81, 83 (AChE), 13, Aberrant learning, 516 synthesis/stabilization/assemble/ 110, 213, 377 AC. See Adenylyl cyclases secretion of ChEs and, alkylphosphorylated, 266 Accountability, 662 123–124 appearance of, 125–126 Acetyl coenzyme A, 39, 82, 86–87 vesicles loading into, 44–45 block of release of, 376 (ACh), 1, 499, 657 as vesicular/cytoplasmic, 86 erythrocytic, inhibition, 508 acetyl CoA, 39, 82, 86–87 Acetylcholine receptors (AChR), globular, 325 axoplasmic transport of CAT 212. See also Muscarinic histochemistry of, 37 and, 88–89 acetylcholine receptors; mammalian, 117 binding protein structure, 216 Nicotinic acetycholine in ontogenesis, 320 binding sites of, 217–218 receptors phosphorylated, 263–265 biphasic effects of release of, 448 diseases caused by mutations in, subclassifi cations of, 115 CAT and, 83–86 225–226 Tc ribbon diagram of, 118 from released, 90 ganglionic, 222 Acetylthiocholine, 35 choline/phosphatidylcholine as neuronal, in nonneuronal tissues, ACh. See Acetylcholine precursor to, 96–100 224–226 AChE. See Acetylcholinesterase cholinergicity notion and, structures of, 215 AChR. See Acetylcholine receptors 439–440 subunit arrangement of, 217 Acquaintance making, 515 electron photomicrographs, 337 Acetylcholine release, 16, 33–42 Activated calmodulin, 285 esterase, 41 classical/unorthodox hypotheses Active (high-affi nity) choline genetics/sequence of ChE of, 49–54 uptake system, 107–108 subunits, 122 classical release model/ Active oximes, 245 hydrolysis of, 110, 122–123 postsynaptic responses, Active proteins, 334 interseptal administration of, 475 49–52 Acyl pocket outline, 117 intraterminal, motions, 44 neoclassical notions of, 52– AD. See Alzheimer’s disease leakage, 52 53 Addiction, 444, 515–521 measurement of, 4 from/in brain/isolated tissues of, alcoholism, 503, 517–519 of, 81–131, 411, 659 437–440 cocaine, 519–520 immediate concerns with, 659 molecular/cellular aspects of, nicotine, 520–521 structures/active sites/ discoveries concerning, 21 opiate, 516–517 mechanism of action of, presynaptic regulation, 16 Adenylyl cyclases (AC), 184–185 114–124 processes of, 19, 40–42 Adrenal medulla, 372 metabolism/synthesis/formation neurons and, Adrenergic , 462 of, 16–18 40–42 Aggression, 491–495 mustard, 177 Acetylcholine transferase, 44 anatomy of, 494 release, immediate concerns Acetylcholinergic human, 492 with, 659–660 pharmacotherapy, 631–637 offensive, 495 release from/in brain/isolated cholinergic therapy and, types of, 492 tissues of, 437–440 632–635 Agonist competition binding, 189

667 668 Index

Agonist-dependent nerve growth factor/ cholesterol/APP processing, phosphorylation, 182 muscarinic cholinergic 611–614 Agonist-promoted analgesia, receptors/GSK3β, 628–629 physiologic effects of 191 NGF regulation of Aβ, secreted, 610–611 Agonists 629–630 mutation of, learning/memory, alphadrenergic, 474 presenilin/GSK3β/axoplasmic 618 catecholaminergic, 494 transport, 626–627 mutations of, 614 cholinergic, 461, 477–487 WNT/GSK3β/β-Catenin/ proteolytic cleavage of, 608– dopaminergic, 462 E-cadherin pathways/ 609 indoleaminergic, 473 presenilin, 622–626 structure of, 608 mAChRs, 164–166. See also α-secretase and, 614–615 traffi cking/axonal transport of, Muscacarinic cholinergic β-secretase and, 615–616 609–610 receptors γ-secretase and, 616–618 Amyloidogenesis, 635 nicotinic, 477 tau isoforms/phosphorylation in, Amyloidogenic processing, 628, serotonergic, 494 619 629 Agrin, 331, 366 therapy of/future directions, Amyloidogenic vicious cycle, 607 AICD. See Amyloid intracellular 631–637 Amyloidosis, 599, 610, 634 domain acetylcholinergic senile, 599 behavior, 518 pharmacotherapy, 631–637 Amyloidosis model. See Beta- Alcoholism, 503, 517–519 widely used transgenic models amyloid cement Alcuronium, 172, 178 of, 612–613 Analgesia, 495–500, 496 Algetic stimulation, 442 Amacrine, 61 agonist-promoted, 191 Aliesterase, 268 Amacrine cells, 42, 325, 422 cholinergic, 498 Alkane derivatives, 172 Amanita muscaria, 153 Analgetic interaction, 497–498 Alkylphosphorylated Amino acid, 491 Androstane derivatives, 172 acetylcholinesterase, 266 Amino acid transmitters, 453 Anesthesia, 456–459 Allosteric interaction, 171 Amitriptyline, 635 Anesthetics, 443 Allosteric modulators, 170–173 Ammonium sulfate fraction, 157 Animal experimentation, 289 Allosterically potentiating ligand Amphetamines, 44 Anoxia, 488 (APL), 455 Amphibia (effects of morphine), Antagonists, 168–170 Alpha adrenergic agonists, 474 496 for mAChRs, 168–170, 509 Alzheimer, Alois, 597 Amygdala, 506 selected, dissociation constants, Alzheimer’s disease (AD), 58, 87, Amyloid 169 110, 255, 260, 370, 522, deposits, 599 Anterograde tropism, 14 657 effects/fi brillogenesis/amyloid Anterograde-acting factors, amyloid precursor protein, plaques, 605–608 370–377 608–614 metabolism, 634 Anterograde-wise-acting amyloid/tau biology linked to, purifi cation of properties of, 605 neurotrophins, 368 597 Amyloid biology, tau biology Anterotrophins, 344 dysregulated processing of linked to Alzheimer’s antiChE. See Anticholinesterase neurocellular proteins, disease, 597–638 actions, learning/ 602–605 dysregulated processing of memory and, 511–515 cholinergic aspects/treatment of, neurocellular proteins, Anticholinesterase (antiChE), 5, 600–602 602–605 11, 109, 237–299, 250, 454, gene mutations/isoforms in, Amyloid effects, learning/memory, 507–510 606 618 agents research history of, history of, 597–599 Amyloid interactions, 630–631 237–246 phosphorylation, 619 Amyloid intracellular domain OP drugs, 242–246 potential regulatory interactions (AICD), 610 pageant of physostigma/ in pathogens in, 622–631 Amyloid plaques, 605–608 naturally occurring, amyloid/tau interactions, Amyloid precursor protein (APP), 237–242 630–631 608–614, 634 cholinergic tetralogy, 290–291 apoptosis/caspase/calsenilins/ functions of, 610–614 cholinergic toxicity of, 273– presenilins, 626 apolipoprotein E 285 GSK3β/tau/amyloidogenic polymorphism/APP acute toxicity of OP AChE, processing, 628, 629 processing, 611 273–276 Index 669

chronic toxicity of OP drugs/ Astrocytes, 92, 435, 506 Beta-amyloid cement (amyloidosis development of tolerance, Atropine, 7, 97, 437, 460, 486 model), 597–599 276–278 insensitivity, 480 Beta-amyloids, 360 delayed toxicities/Gulf War Atropinic activity, 451 Bethanecol, 165 Syndrome/delayed cognitive Atropinic drugs, 463, 507–510 Better-characterized gallamine- toxicity/OP-induced delayed Autocatylitic reaction, 605 binding, 172 /delayed Autoinhibition, 155 Biochemical phenomena, 453, 454 pulmonary toxicity, Autonomic ganglia, 152, 209, Biquaternary compounds, 252 278–285 327–329 Bivalent receptor ligands, 166 classifi cation/chemical/structure- Autonomic ganglia neuron, 214 Blood ChEs, 414 activity relationships/ Autoreceptors, 429–431 Blood fl ow responses, 470 bonding of, 246–257 cholinergic, 429–431 Blood phosphatidylcholine, 94 naturally occurring/ muscarinic, 430 Blood plasma, 102–104 , 246–252 nicotinic, 430 Blood pressure, 521 structure-activity relationships/ Autosomal dominant nocturnal Blood-brain barrier transport, bonding, frontal lobe epilepsy 108–109 252–256 (ADNFLE), 225 Blood-brain-barrier (BBB), 108, 611 globular, 325 AVD. See Arteriovenous difference BMPs. See Bone morphogenetic metabolism/detoxifi cation of, Aversive syndrome, 463 proteins 267–272 Avian neurogenesis, 322 Bolus, 238 non-OP antiChEs toxicity Avian parasympathetic ganglia, 327 Bonding treatment, 290 Avoidance conditioning climbing of antiChE, 246–257 organophosphorus, 243–244, screen, 501 carbamate, 252–256 260–271, 273–276 Awakening of arousal, 483–487 of organophosphorus other, 265–267 Axial notochord, 379 anticholinesterases, phosphorylated, aging, 262–263 Axin, 623 260–261 related synthetic, 246–252 Axogenesis, 329 Bone morphogenetic proteins structure-activity/bonding of OP, Axon collateral, 419 (BMPs), 333 260–261 Axonal degeneration, 368, 374 Bovine rhodopsin, 180 toxic effects of, 272–285 Axonal plasma membrane, 368 Brain treatment of poisoning from, Axons, 42 ACh release in, 437–439 288–291 Axoplasmic fl ow, 88–89, 368, 373 active states of, 481 prophylaxis/OP drugs Axoplasmic transport, 88–89 choline distribution and, treatment, 288–290 103–104 Antimuscarinics, 509 B choline transport into, 90 Anxiety-related behavior, 190 Bacteria, 151–153 free synaptotropic, choline, 94 Anxiolytics, 523 Baroceptor refl ex, 460 Brain active states, 481 Apolipoprotein E polymorphism, Basal forebrain Brain choline, 93–95 611 cholinergic neurons in, 63 Brain interstitial water, 103 Apoptosis, 626, 627–628 cholinergic projections of, 66 Brain ischemia, 436 APP. See Amyloid precursor Basal forebrain cholinergic Brain phospholipids, 91–93 protein neurons, 188 Brain rhythms, 477–491 Aquatic larval urodeles, 276 Basal lamina, 124, 331 awakening of arousal/sleep ARAS. See Ascending reticular Basal locomotor activity, 191 phases/cholinergic agonists/ alerting system Basalis magnocellularis, 430 antagonists, 483–487 Arecoline, 165, 413, 466 Basement membrane, 331 central nervous system seizures/ Arginine, 465 Basic globular protein, 85 cholinergic system, Arteriovenous difference (AVD), 95 BBB. See Blood-brain barrier 487–490 Artifi cial cerebrospinal fl uid, 438 BDNF. See Brain-derived chronobiology, 490–491 Arylesterases, 267 neurotrophic factor EEG patterns/evoked potentials/ Ascending cholinergic pathways, 64 Behavioral functions, 456 cholinergic agonists/ Ascending cholinergic radiations, Benzenesulfonyl fl uoride (BSF), antagonists effects, 39 253 477–483 Ascending reticular alerting system Benzisoxazoles, 255 endogenous activity of (ARAS), 34–35 Benzylpiperidines, 255 cholinergic neurons, 477 Ascorbic acid, 331 Beta-adrenergic blockers, 463 theta rhythm, 479–481 670 Index

Brain-derived neurotrophic factor CCK. See Cholecystokinin historical introduction to, (BDNF), 343, 362, 630 Cell(s) 412–426 Bronchometer tone, 460 adhesion molecules, 330, 366 discontinuity of early story, BSF. See Benzenesulfonyl fl uoride amacrine, 42, 325, 422 412 BuChe. See Butyryl cholinesterase cholinergic, 33–69 early studies of nicotine/ Butcher, L. See Cholinergic cochlear hair, 213 physotigmine/related pathways crest migration, 328 substances, 413–415 Butyryl cholinesterase (BuChe), death, 334, 349 Eccles’ conversion/ 13, 110, 127, 262, 424, 658 ganglion, 347, 422 demonstration of central AChE and, 377 glutaminergic, 48 cholinergic transmission/ isozymes of, 112 MAP-2-enriched certain pertinent Butyrylcholine, 110 cholinoreceptive, 528 generalizations, 415–422 gorge, 121 nerve, 420 post-Ecclesian cholinergic Butyrylthiocholine, 35 neural crest, 327 studies/their topics, noncholinoreceptive, 427 422–426 C purkinje, 36 immediate concerns with, Caerulein, 448 Renshaw, 13, 415, 419, 449 657–662 Calabar bean extract, 7, 109, 413 Schwann, 369 ACh metabolism, 659 effects of, 239 spinal cholinoreceptive, 457 central cholinergicity, Calcium channels, 187–188 Central chemical transmission, 417 660–662 Calmodulin, 50 Central cholinergic nervous channels, 660 Calsenilins, 626 system, 411–529 cholinergic neuron/ACh cAMP-response element binding central ACh release, 437–440 release, 659–660 (CREB), 630 cholinergicity notion and, cholinergic pathways, 658 CANB. See Cholinergic Alert 439–440 cholinesterases, 658 Behavior from/in brain/isolated tissues, clinical aspects, 657–658 Canberra group, 420 437–439 development/phylogenesis, Cannabinoids, 498 cholinergic aspects of organism/ 658–659 Carbachol, 165, 485 environment interaction, receptology, 660 Carbamates, 246–252 523–529 mental/behavioral functions with Carbamic acid, 113 cholinergic alert nonmobile cholinergic implications, Carbamylation, 241 behavior, 523–525 491–523 , 248, 379 immense complexity/dualism/ addiction, 515–521 , 248 reductionism, 525–529 aggression, 491–495 Carboxylesterases, 269 cholinoreceptive responses, cholinergic antinociception/ Cardiovagal perfusate, 15 426–437 analgesia, 495–500 Cardiovascular controlled central postsynaptic memory/learning/cognition, phenomena, 468–471 cholinoreceptive responses/ 500–515 Cartesian microdriver, 111 their characteristics, other behaviors, 521–523 Caspase, 626 431–437 of central CAT. See Choline acetyltransferase post/presynaptic/occurence in cholinergic responses/ Cat superior cervical ganglion, 81 cholinergic pathways, cholinomimetic responses, Cataleptic action, 496 427–431 440–455 Catecholamine release, 444, 445 far beyond matters, 662–665 scope of chapter of, 411–412 Catecholaminergic agonists, 494 accountability of cholinergic Central cholinergic neurons, 42–49 Catecholaminergic link, 461 functions/behaviors, 662 Central cholinergic pathways, 34– Catecholaminergic pathways, 463 consciousness, 662–663 40, 55–69, 412 Catecholaminergic-cholinergic functional aspects of, 455–491 development of, 33–40 interactions, 451 brain rhythms/sleep/related Central cholinergic system, 424 Catecholamines, 277, 411 phenomena, 477–491 Central cholinergic system Catechol-o-methyltransferase, 89 central functions/organic research, outline of history β-catenin, 622–626 behaviors with cholinergic of, 7–24 Cation channel, 218–219 implications, 456–464 Central cholinergic transmission, Caudate putamen, 174 cholinergic effects concerning 440 CBGD. See Corticobasal ganglion hypothalamus/homeostatic demonstration of, 415–421 degeneration function, 464–477 fanfares and correlates of, 16–21 Index 671

metabolism/synthesis/ Cerebrospinal fl uid (CSF), 101, ACh and, 83–86 formation of ACh into 103 axoplasmic transport of, 88–89 release mode, 16–18 artifi cial, 438 with CoA, 39 Central cholinergicity, 25 choline distribution, 103–104 intracellular activity in, 84 immediate concerns with, Cerulein, 448 single gene for, 85 660–662 Cervical somite contractions, 379 Choline administration, 375 Central electrophysiology, 26 Channel-receptor macromolecules, Choline containing lipids, 83 Central excitatory muscarinic 332 Choline distribution, 102 responses, 431–436 Characteristic protein alterations, active (high-affi nity) choline Central excitatory nicotinic 603–604 uptake system of RBCs, responses, 431–436 Chemical transmission, 11 107–108 Central functions Chemical transmitter, 420 blood plasma and, 102–104 with cholinergic implications, Chemoreceptive trigger zone brain and, 103–104 456–464 (CTZ), 461 cerebrospinal fl uid and, 103 emesis, 461 Chemoreceptors, 460 erythrocytes, 102–103 motor function, 461–464 Chemotaxic infl uence, 345 other tissues and, 104 respiratory phenomena, 459–461 ChEs. See Cholinesterases Choline ester hydrolysis, 113 Central inhibitory postsynaptic Cheyne-Stokes respiration, 275 Choline esters, 128 cholinoreceptive responses, Chick ciliary ganglion, 328 Choline high-affi nity uptake, 436–437 Chicken imprinting, 522 104–107 Central nAChRs, 222–223 Chiral drugs, 155 Choline infl ux-effl ux, 95 Central nervous pathways, 421 Chlolinergic aspects of growth/ Choline metabolism, 90 Central nervous system (CNS), 1, development, 311–381 Choline transport 316, 627 Chloride channels, 188 into brain, 90 anatomical studies of peripheral, Cholecystokinin (CCK ), 448 historical introduction to, 152 Cholera, 239 100–101 chemical transmission in, 11 Cholesterol, 102, 611–614 Choline uptake, 16, 17, 93–95, muscarinic acetylcholine Choline 100–109 receptors, 163–193 as ACh precursor, 96–100 historical introduction to, molecular biology of, blood-brain barrier transport and, 100–101 175–182 108–109 low-affi nity, 108–109 pharmacological classifi cation, brain, 93–95 Choline uptake system, active 163–173 brain phospholipids and, 91–93 (high-affi nity), 107–108 signaling pathways, 183–190 dietary, 90–91 Cholinergic actions, learning/ muscarinic receptors in, 427 distribution of, in brain tissue, memory and, 511–515 Central nervous system seizures, 92 Cholinergic agents 487–490 free synaptotropic brain, 94 on anesthesia/refl exogenic Central NGF, 349–352 glycerophosphoryl, 93 action, 456–459 Central paralysis, 412 homo, 47 tetralogic/ontogenetic effects of, Central postsynaptic lines of defense against excess, 377–380 cholinoreceptive responses, 95 Cholinergic agonists, 461, 477– 431–437 metabolism of, 82, 90 483, 483–487 central excitatory muscarinic/ metha, 123 Cholinergic Alert Behavior nicotinic responses, as phospholipid precursor, (CANMB), 19 431–436 96–100 Cholinergic alert nonmobile central inhibitory postsynaptic phosphoryl, 92, 265 behavior (CANMB), 461, cholinoreceptive responses, phosphorylated, 91 523–525, 525 436–437 pyrrolidine, 47 Cholinergic analgesia, 498 Central presynaptic regulation, 440 quaternary nitrogen of, 84 Cholinergic antagonists, 477–483, Central synaptogenesis, 332–334 from released ACh, 90 483–487 Centrally controlled succinyl, 24 Cholinergic antinociception, 495– gastrointestinal/urinary/ traffi c of, 92 500, 497 enteric activity, 471 triethyl, 48 analgetic interaction, 497–498 Cephalods, 339 Choline acetyltransferase (CAT), cannabinoids/cholinergic Cerebral cortex, 481 13, 23, 83–86, 327, 417, analgesia, 498 Cerebral Purkinje neurons, 437 600, 658 sensorium, 499–500 672 Index

Cholinergic ascending reticular of endocrine function, Cholinergic ontology, 25 alerting system, 34–35 464–468 precocious developmental Cholinergic aspects, 600–602 sexual behavior, 475–477 appearance of components Cholinergic autoreceptors, 429–431 thermocontrol, 471–473 of cholinergic system, Cholinergic axons, 42 thirst/hunger control, 473–474 314–319 Cholinergic basal forebrain concerning hypothalamus/ cholinergic components as neurons, 505 homeostatic function, morphogens, 317–319 Cholinergic behaviors, 17, 662 464–477 gametal/preneuronal Cholinergic brain systems, 507 Cholinergic functions, 634, 662 appearance of components Cholinergic cells, 33–69 Cholinergic gene locus, 17 of, 314–317 ACh release, classical/ Cholinergic heteroreceptors, 430, Cholinergic pathways, 33–69 unorthodox hypotheses of, 445 as defi ned by recent 49–54 Cholinergic hypofunction, 634 investigators, 65–68 central cholinergic neurons, Cholinergic identifi cation, 56 development of, 33–40 morphology/cytoanatomy/ Cholinergic implications, 456 cholinergic ascending reticular markers of, 42–49 Cholinergic learning circuitry, 514 alerting system, 34–35 of medial septum, 57 Cholinergic lore, 25 Dale/Feldberg on existence of, methodologic development Cholinergic markers, 40–42 33–34 history for, 33–42 Cholinergic morphogenesis, 375 defi nitive description of, in retina, 61 Cholinergic mossy fi bers, 338 35–40 Cholinergic cholinoceptive neuron, Cholinergic nerve terminal actions, diagrammatic representation of, 33 447 64 Cholinergic components Cholinergic nerve terminals, 19, immediate concerns with, 658 as morphogens, 317–319 86, 429 introduction to, 55 tetralogic/ontogenetic effects of, Cholinergic neurogenesis, in McGeer presentation of, 55–65 377–380 sensory brain areas, McGeers’ medial forebrain tetralogic/toxic actions of, 325–326 system, 57–58 378–380 Cholinergic neurons, 11, 33–42, McGeers’ motor nuclei, 60 Cholinergic correlates, 473–474 40–42, 54, 101, 323, McGeers’ parabrachial of behavioral cognition/ 650–660 complex, 58–59 consciousness/ acetylcholine release and, 40–42 McGeers’ reticular system, electrophysiological in basal forebrain, 63 59–60 counterparts, 19–20 cholinergic markers in McGeers’ striatal centrally controlled noncholinergic cells/tissues, interneurons, 60 gastrointestinal/urinary/ 48–49 McGeers’ and Woolf-Butcher enteric activity, 471 cycling/recycling processes of, presentation, 61–68 of endocrine function, 464– 44 pathway maps, 61–65 468 ACh loading into vesicles, Mesulam presentation of, sexual behavior, 475–477 44–45 62–68 thermocontrol, 471–473 docking/fusion, 45–46 methodologic development Cholinergic dendrites, 62 formation/movement of, 44 history for, 33–42 Cholinergic desynchronization, postsynaptic membranes/ modern study methods for, 55 482–483 cholinergic receptors, post/presynaptic cholinoreceptive Cholinergic developmental system, 46–47 responses in, 427–431 14 synaptic vesicles, cycling/ representation of, 426 Cholinergic drugs, 7, 456 recycling of, 47 ubiquity of, 411 Cholinergic EEG, 525 endogenous activity of, 477 Cholinergic pharmacology arousal, 478–479 false transmitters for, 47–48 postsynaptic, 442–443 phenomena, 17 neurochemical systems as presynaptic, 440–441 Cholinergic effects, 371–377 markers of, 44 Cholinergic phylogeny, 25 cholinergic correlates release processes for, 48 Cholinergic projections, 66 cardiovascular controlled Cholinergic nicotinic receptors, Cholinergic receptology, 4 phenomena, 468–471 330 Cholinergic receptors, 46–47 centrally controlled Cholinergic non-mobile behavior nicotinic/muscarinic, 151–159 gastrointestinal/urinary/ (CNDB), 487 in rodent neurogenesis, 321 enteric activity, 471 Cholinergic ontogeny, 338–339 Cholinergic regeneration, 358 Index 673

Cholinergic regulation, 19 between motoneuron/Renshaw presynaptic cholinoreceptivity/ Cholinergic research, 24 cell, 13 actions of cholinergic Cholinergic reticular system, 37 muscarinic cholinergic receptors autoreceptors, 429–431 Cholinergic signaling, 221 and, 154 Cholinoreceptive targets, 62 Cholinergic spinal neuron, 457 Cholinergic treatment of AD, Cholinoreceptivity, 25, 40, 41 Cholinergic synapses, 36, 424, 426 600–602 inhibitory, 437 Cholinergic system, 453, 487–490 Cholinergic vagal system, 318 muscarinic/nicotinic, 426 anterograde-acting factors/related Cholinergic vesicles, 44 postsynaptic, 427–429 phenomena, 370–377 Cholinergic-cholinergic relays, 59 Chorionic villi, 126 transsynaptic effects/ Cholinergicity notion, 439–440 Chromaffi n, 347 cholinergic effects as Cholinesterase inhibitor, 439 Chromatography-mass synaptogens, 371–377 Cholinesterase reactions, inhibitors/ spectrometry (GCMS), 13 brain rhythms of, 487–490 substrates, 112–114 Chronic morphine administration, of cholinergic system during Cholinesterases (ChEs), 10, 109– 516 neurogenesis/organogenesis 114, 657. See also Chronobiology, 490–491 central synaptogenesis, Acetylcholinesterase; Ciliary ganglion, 363 332–334 Butyryl cholinesterase Ciliary neurotrophic factor cholinergic neurogenesis in active sites of, 112–114 (CNTF), 343, 362–364 sensory brain areas, anticholinesterases/cholinergic purifi cation of, 363 325–326 transmission, 109 Ciona intestinalis, 126 functional differentiation/ blood, 414 Ciona ontogenesis, 315 synaptogenesis, 326–332 classifi cations/types/variants of, Clathrin, 182 development of, during 109–112 Clonidine, 444 neurogenesis/organogenesis, distribution of, 124–127 Cloning, 85 319–335 embryonic, 377 Clostridial , 46 early neurogenetic appearance/ fundulus hetercolitus relationship Clostridial toxin cleavage sites, 46 subsequent rate of to, 313 CMS. See Congenital myasthenic development, 319–320 immediate concerns with, 658 syndromes neurogenesis, 320–325 mechanism of enzymic, action, CNS. See Central nervous system gametal/preneuronal components 122–123 CNTF. See Ciliary neurotrophic of, 314 myosin, 126 factor modulates, 491 postfertilization/preneural CoA. See Coenzyme A neurogenetic appearance of, 320 presence of, 315 Coagulation factor, 610 phylogenesis of, 339–340 roles of, 127–130 Cocaine addiction, 519–520 retrophic factors of, 361–370 specifi c, 110 Cochlear hair cells, 213 gangliosides, 367–369 synthesis/stabilization/assemble/ Coenzyme A (CoA), 39 growth factors acting on secretion of, 123–124 acetyl, 82, 86–87 nervous system, 364–365 Cholinomimetic sensitivity, 326 Cognition, 500–515 neurokines/ciliary Cholinomimetics, 437 cholinergic correlates as, 19–20 neurotrophic factor, Cholinoreceptive inhibitory sites, kinds/components of, 504–505 362–364 460 methodology of, 500–504 neurotrophins, 361–362 Cholinoreceptive neurons, 426, muscarinic/atropinic drugs/ nonneurotrophic elements 456–457 antiChEs, 507–510 concerned with Cholinoreceptive responses, nicotinics/nicotinolytics, neurogenesis/ 426–437 510–511 synaptogenesis, 365–367 central postsynaptic Collagen, 224 Cholinergic teratology, 290–291, cholinoreceptive responses/ Collapsing response mediator 314 their characteristics, protein (CRMP-2), 619 Cholinergic therapy, 632–635 431–437 Collier, B., 106 Cholinergic toxicity, 273–285 ionic characterization of, 434 Commisural, 503 Cholinergic transmission, 109, 423 post/presynaptic/occurence in Complementarily, 112 brief story of studies of, 7–16 cholinergic pathways, Complex emetic processes, 461 demonstration of, 10 427–431 Complex hyperphosphorylates tau, molecular/cellular aspects of, postsynaptic 626 18 cholinoreceptivity, 427– Concomitant glycogenoytic effect, discoveries concerning, 21 429 469 674 Index

Congenital myasthenic syndromes Delayed pulmonary toxicity (DPT), NGF and, 341–361 (CMS), 224–225 278–285 normal/lithium inhibited Consciousness, 19–20, 662–664 Dementia, 167 echinoderm, 315 Constituent nuclei, 37 Dendrites, 62 postnatal neurogenesis, 335– Contextual fear learning, 618 Dendritic branching, 333, 512 338 Convulsions. See Seizures Dendritic interactions, 528 retrophic factors of, 361–370 Cortical cyctoarchitecture, 374 Dendritic remodeling, 333 gangliosides, 367–369 Cortical discharges, 490 Dendritic reorganization, 512 growth factors acting on Cortical EEG desynchronization, Dendroaspis angusticeps, 168 nervous system, 364–365 478–479 Denervation, 373 neurokines/ciliary Cortical laminae, 174 Dentate gyrus, 607 neurotrophic factor, Cortical slab preparations, 490 Department of Defense (DOD), 362–364 Corticobasal ganglion degeneration 272, 286 neurotrophins, 361–362 (CBGD), 602 Department of Health and Human nonneurotrophic elements Corticosteroids, 452, 466 Services (DHHS), 521 concerned with Corticothalamic efferents, 227 Depolarization, 452 neurogenesis/ CREB. See cAMP-response Depressed amino acid-induced synaptogenesis, 365–367 element binding excitation, 449 Dexetimide, 156 Crest cell migration, 328 Desensitization, 213, 436 DFP. See Diisopropylfl uorophos- CRMP-2. See Collapsing response Desynchronization phonate mediator protein cholinergic, 482–483 DHHS. See Department of Health Cryoelectron microscopy, 218 cortical EEG, 478–479 and Human Services C-terminal fragments (CTFs), 608 muscarinic, 479 Diagonal band pathways, 449 CTFs. See C-Terminal fragments Desynchronized state supervenes, Dialysis tubings, 422 CTZ. See Chemoreceptive trigger 483 Dienchephalon, 335 zone Detergent-insoluble-glycolipid Dietary choline, 90–91 Curarimimetics, 266 (DIG)-enriched fractions, 614 DIG. See Detergent-insoluble- Cyclin-dependent kinase 5, Development glycolipid (DIG)-enriched β-catenin, 625–626 anterograde-acting factors/related fractions Cycling processes, 44 phenomena, 370–377 Dihydro-beta-erythroidine, 419 Cytidine disphosphocholine, 93 transsynaptic effects/ Diisopropylfl uorophosphonate Cytoplasmic carboxyl terminus, cholinergic effects as (DFP), 23, 34, 107, 237, 176 synaptogens, 371–377 424 cholinergic aspects of, 311–381 Dinitrophenol (DNP), 450 D cholinergic ontology, precocious Disease(s). See also Alzheimer’s 4-diphenyl-acetoxy-N-Methyl developmental appearance disease (AD) piperidine methiodide of components of Lou Gehrig’s, 287 (4-DAMB), 158 cholinergic system, neurodegenerative, 603–604 DAG. See Diaclyglycerol 314–319 Parkinson’s, 193, 370, 522 Dale, Henry, 8, 33, 109 of cholinergic pathways, 33–40 peripheral cholinergic, 481 DCT. See Delayed cognitive of cholinergic system during Disrupted neuronal functions, 605 toxicity neurogenesis/organogenesis, Divorce phenomenon, 525 Deacetylation process, 123 319–335 Dixon, W.E., 2, 7 Dealkylation, 263 central synaptogenesis, DNP. See Dinitrophenol Deanol, 96 332–334 Docking, 45–46 Decamethonium, 24 cholinergic neurogenesis in DOD. See Department of Defense Deep surface sensory brain areas, , 632 electroencephalograms, 325–326 Dopamine, 520 476 early neurogenetic appearance/ Dopaminergic agonists, 462 Defi cital cholinergic function, 355 subsequent rate of Dopaminergic blockers, 463 Degeneration development, 319–320 Dopaminergic neurons, 226 axonal, 368, 374 functional differentiation/ Dopaminergic transmission, 522 CBGD, 602 synaptogenesis, 326–332 Dorsal hippocampi, 422 granulovacular, 620 neurogenesis, 320–325 Dorsal root ganglia, 359 Delayed cognitive toxicity (DCT), immediate concerns with, Dorsal tegmentum, 443 273 658–659 Dorsal vagal complex (DVC), 471 Index 675

Dorsomedial striatum, 511 Endocrine function, 464–468 Exogenous gangliosides, 368 Down syndrome, 614 Endocytosis, 182 Experimental autoimmune MG Drosophila, 340 Endoplasmic reticulum (ED), 123, (EAMG), 210 Drosophila melanogaster, 313 609 Expressed receptor protein, 173 Drugs Endoplasmic reticulum associated Extracellular amino termini, 176 addiction to, 444 degradation (ERAD), 123 Extracellular amyloid fi brillar adrenergic, 462 Endorphins, 453 aggregates, 606 atropinic, 463, 507–510 Endosomes, 615 Extracellular dopamine release, chiral, 155 Endplate potentials (EPPs), 441 191 cholinergic, 7, 456 Enriched environment, 511 Extracellular-signal regulating homochiral, 155 Enteric activity, 471 kinase-mitogen-activated muscarinic, 507–510 Entorhinal cortex, 449, 610 protein (ERK/MAPK), 510 opioid, 495 Environmental Projection Agency -seeking behavior, 516 (EPA), 246 F d-TC. See d-Tubocurarine Enzyme(s), 39, 151–153 False transmitters, 47–48 Dualism, 525–529 acetyl CoA, 82, 86–87 Familial frontal lobe epilepsy, 489 DVC. See Dorsal vagal complex adenylyl cyclases, 184–185 , 123 Dynamin, 182 erythrocytic, 110 Fasciculus retrofl exus, 214 Dyskinesia, 522 iso, 83, 85 Fast axonal transport, 89 Dysregulated processing, 602–605 mitochondrial acetyl co, 89 Fast vesicle recycling, 54 Dystrophic neurites, 606 mitogen-activated protein kinase Fat metabolism, 102 pathways, 185–186 FDA. See Food and Drug E nitric oxide synthase, 185 Administration EAMG. See Experimental phospholipases, 184 Fear, 521, 618 autoimmune MG phosphorylated, 261–262 Feldberg, W., 2, 3, 11, 13, 17, 19, Early muscle fasciculations, 275 postsynaptic, 36 24, 244, 412, 417, 423–425, Eccles, John, 1, 54, 81, 109, presynaptic, 36, 128 438, 451 415–426 EPA. See Environmental Projection FGFs. See Fibroblast growth conversion of, 415–421 Agency factors Echinoderm development, 315 Epidermal growth factor (EGF), Fibrillogenesis, 605–608 ED. See Endoplasmic reticulum 186, 365 Fibroblast growth factors (FGFs), EEG. See Electroencephalogram Epileptic foci, 163 364 EGF. See Epidermal growth factor Epileptiform kindling, 444 FIFRA. See Fungicide and Elastin, 224 EPP. See Excitatory endplate Rodenticide Act Electric transmission, 416 potentials Fifth postnatal week, 336 Electroencephalogram (EEG), 17, EPPs. See Endplate potentials Flavobacterium, 270, 271 19, 411 EPSP. See Excitatory postsynaptic Focal lysis, 220 cholinergic, 525 slow potential Follicle stimulating hormone cholinergic arousal of, 478–479 ERAD. See Endoplasmic reticulum (FSH), 467 cortical, desynchronization, associated degradation Food and Drug Administration 478–479 ERK/MAPK. See Extracellular- (FDA), 631 deep surface, 476 signal regulating kinase- Forebrain lesions, 364 evoked/synchronized potentials, mitogen-activated protein Free motor behavior, 462 481–482 Erythrocytes, 102–103 Free synaptotropic brain choline, patterns of, 477–483 Erythrocytic enzyme, 110 94 Electrolyte transport, 186 Esoteric protein sites, 284 Frontotemporal dementias (FTD), Electron photomicrographs, 337 Ethiological aggression types, 493 602 Electrophoresis, 419, 423 Evoked EEG potentials, 481–482 FSH. See Follicle stimulating Electrophorus electricus, 210 Evoked potentials, 477–483 hormone Electrophorus plaque, 158 Excitatory amino acids, 491 FTD. See Frontotemporal Electroplaque membrane, 157 Excitatory endplate potentials dementias Electroshock, 489 (EPP), 331 Functional differentiation, 326–332 Embryo, 319 Excitatory postsynaptic slow autonomic ganglia, 327–329 Embryonic cholinesterase, 377 potential (EPSP), 50–51, heart, 326–327 Emesis, 460 432, 433 motoneuron/myneural junction, Encephalopathies, 87 Exocytosis, 47 329–332 676 Index

Functional heteromeric oligomers, Ganglionectomy, 360 cholinergic aspects of, 311–381 119 Ganglionic AChRs, 222 cholinergic ontology, precocious Functions, 221–228, 326–332. See Ganglionic blockers, 245 developmental appearance also Central cholinergic Ganglionic stimulation, 81 of components of nervous system; Central Ganglionic transmission, 24, 227 cholinergic system, functions Gangliosides, 367–369 314–319 of APP, 610–614 exogenous, 368 parsimonious axonal, 340 behavioral, 456 major brain, 367 postnatal neurogenesis, 335–338 cholinergic, 634, 662 on nonneural tissues, 369 retrophic factors of, 361–370 defi cital cholinergic, 355 regenerative trophic actions of, 368 gangliosides, 367–369 disrupted neuronal, 605 Gastrointestinal activity, 471 growth factors acting on endocrine, 464–468 Gene induction, 186 nervous system, 364–365 general mopping up, 127 General mopping up function, 127 neurokines/ciliary homeostatic, 464–477 Geneserine, 17, 246, 340 neurotrophic factor, hypo, 634 Genetic mechanisms, 277 362–364 mental, 456 GIRK. See G protein inward- neurotrophins, 361–362 motor, 461–464 rectifying potassium nonneurotrophic elements of NGF, 345–361 Gland, 125 concerned with psychological, 456 submandibular, 371 neurogenesis/ suraspinal cholinergic, 471 submaxillary, 127 synaptogenesis, 365–367 Fundulus hetercolitus, 313, 316 Glia, 215 trophic factors with, 340–341 Fungicide and Rodenticide Act Glia-derived neurotrophic factor GSK3β. See Glycogen synthase (FIFRA), 246 (GDNF), 364 kinase 3β Fungicides, 241 Globular AChE, 325 Guanine-nucleotide-binding Fusion, 45–46 Globular amphiphilic forms, 127 protein-coupled receptor Glucose metabolism, 471 (GPCR), 163, 623 G Glucosides, 153 Gulf War Syndrome (GWS), 272, G protein inward-rectifying Glutamate, 121, 222–223, 369, 451 278–287 potassium (GIRK), 186 Glutaminergic cells, 48 GWS. See Gulf War Syndrome G protein-coupled receptor kinases Glutaminergic lesions, 463 (GRKs), 181 Glutaminergic neurons, 451 H G proteins, 183–184 Glycerophosphorylcholine, 93 HACU. See High-affi nity choline Galanine, 448 Glycerophosphoryl-choline uptake Galanthamine, 239 diesterase, 93 HCHWA-D. See Hereditary Galanthus, 237 Glycogen synthase kinase 3β cerebral hemorrhage with Galanthus woronowii, 250 (GSK3β), 619–621, 623, amyloidosis-dutch type Gallium, 178 627–629 Head ganglion, 425 Gametogenesis, 322 Glycophosphatidylinositol (GPI), Heart, 326–327 Ganglia, 320 114, 118 Heidenhain, 109 autonomic, 152, 209, 214, Glycoprotein, 366 Hemicholinum, 16, 17, 497 327–329 Glycoprotein sciatin, 330 story of, 101 avian parasympathetic, 327 Glycosaminoglycans, 120 Heparin, 120 dorsal root, 359 Goal-directed behavior, 504 Hepatic transferases, 270 hyperplasia of, 345 Golgi complex, 181 Hereditary cerebral hemorrhage sensory, 345–349 Gonadotrophic hormones, 477 with amyloidosis-dutch type sympathetic autonomic, 432 GPI. See Glycophosphatidylinositol (HCHWA-D), 610 Gangliogenesis, 328 G-protein coupling, 164, 179–181 Heterodimerization, 189, 617 Ganglion(s) Granulovacular degeneration, 620 Heteromers, 118 basal, 57, 100 GRKs. See G protein-coupled Heteroreceptor presynaptic cat superior cervical, 81 receptor kinases cholinergic action, 457 cells, 347, 422 Growth Heteroreceptors, 430, 445 chick ciliary, 328 anterograde-acting factors/related Hexamethonium, 469 ciliary, 363 phenomena, 370–377 High nicotine sensitivity, 226 head, 425 transsynaptic effects/ High performance liquid rabbit parasympathetic/ cholinergic effects as chromatography method, sympathetic, 428 synaptogens, 371–377 439 Index 677

High-affi nity choline uptake Hypertension, 468 sites of expression of functional, (HACU), 105–107, 332 Hyperthermia, 472 447 High-affi nity receptors, 352–353 Hyperthyroidism, 110 striatal, 60 Hippocampal lesions, 358, 422 Hypofunction, 634 Interstitial cell stimulating hormone Hippocampal theta rhythms, 523 Hypokinesia, 462 (ICSH), 467 Hippocampus, 33, 191, 335, 608 Hypoplasia, muscle, 379 Intracerebroventricular Histochemical staining techniques, Hypothalamic ergotrophic, 425 administration, 357 39 Hypothalamic nuclei, 62 Intramembrane-cleaving proteases Histochemistry, 55 Hypothalamic release factors (I-CLiPs), 616 Homeostasis, 101 (HRFs), 466 Intraocular pressure, 260 Homeostatic function, 464–477 Hypothalamic-cortical discharges, Intra-oocytic responses, 316 Homochiral drugs, 155 425 Intraterminal ACh motions, 44 Homocholine, 47 Hypothalamic-hypohyseal system, Invertebrate neurons, 50 Homodimers, 190 467 Ion channels, 186–190 Homogenate-based binding assays, Hypothalamohypophyseal, 464 calcium channels, 187–188 173 Hypothalamus, 425, 464–477 chloride channels, 188 Homogenous radiations, 427 rostral, 473 potassium channels, 186–187 Homomeric forms, 115 Hypothyroidism, 110 IPSP. See Inhibitory postsynaptic Hormones Hypoxia, 436 potential FSH, 467 Ischemia, 436 Gonadotropic, 477 I ISCM. See Central nervous system ICSH, 467 I-CLiPs. See Intramembrane- Isoenzymes, 83, 85 melanin-concentrating, 192 cleaving proteases Isoenzymic character, 83 neurohypophysial, 423 ICSH. See Interstitial cell thyrotropin-releasing, 445 stimulating hormone K Horseradish peroxidase (HRP), 36 IGF. See Insulin-like growth factor Karyotic motoneuron, 330 Hox genes, 340 ILK. See Integrated-linked kinase Kertinocytes, 213 HRFs. See Hypothalamic release Immature neuromyal junction, 330 Kinase(s) factors Immense complexity, 525–529 cyclin-dependent 5, 625–626 HRP. See Horseradish peroxidase Immunocytochemical approach, ERK/MAPK, 510 Human aggression, 492 506 g protein-coupled receptor, 181 Human experience, 289–290 Immunoisolation studies, 214 GSK3β, 619–621, 623, 627–629 Huperzia serrata, 239, 250 Immunoreactivity, 174, 429 integrated-linked, 629 Huperzine, 239, 255–256 Immunosympathectomy, 349 MAPK, 185–186 Huperzine serrata, 237 Imprinting, 622 multiple, 625 Hydrogen bonding, 117 Indoleaminergic agonists, 473 Kinesin, 627 Hydrolases, 268 Inhibitory brain sites, 494 Kinesin light chain (KLC), 619 Hydrolysis, 123 Inhibitory cholinoreceptivity, 437 Knockin mice, 226–228 of ACh, 110, 122–123 Inhibitory postsynaptic potential Knockout mice, 190–193, 214, phospholipid, 95 (IPSP), 417 226–228 Hydrophilic channels, 86 Inhibitory synapses, 488 receptor defi cient, 509 Hydrophobic girdle, 218 Inhibitory transmitters, 435 Kolliker-Fuse nuclei, 58 Hydrophobic substituents, 254 Insecticides, 378 Hydroxyl, 249 Insulin, 125 L Hydroxylamine, 245 Insulin-like growth factor (IGF), Lamina, 116 Hydroxylase, 98 365 Laminins, 46, 331 Hydroxymates, 245 Integrated-linked kinase (ILK), Langley, J., 2, 4, 7, 240, 426 Hydroxymethylglutaryl CoA 629 Large cytoplasmic domain, 220 reductase, 635 International Symposium on Lashley’s electrifi ed jumping stand, Hydrozoa, 311 Cholinergic Mechanisms 524 Hypermotility, 517 (ISCM), 5 Lashley’s electrifi ed stand, 524 Hyperphosphorylation, 622, 631 International Union of Lateral gastrocnemius muscles, Hyperplasia, morphologic, 346 Biochemistry, 112 420 Hyperpolarization, 105, 419, 435 Interneurons Lateral hypothalamic nuclei, 465 Hypersensitization, 372, 373 nicotinic responses of, 446 Lateral reticular nucleus, 61 Hypersynchrony phenomenon, 490 Renshaw, 434 Laterodorsal tegmental nuclei, 67 678 Index

Learning, 500–515 Low-molecular-weight Medial forebrain complex, 422 aberrant, 516 microtubule-associated- Medial habenula, 62 amyloid effects/mutation of weight protein, 618 Medial pontine reticular formation, APP/PS1, 618 LTE. See Long-term enhancement 459 atropinics on, 509 LTP. See Long-term potentiation Mediated vasodilation, 470 cholinergic/anticholinergic action Lycopodium selago, 250, 290 Megacystis-microcolon-intestinal mechanisms on, 511–515 Lymphoid enhancer factor (LEF), hypoperistalsis syndrome, cholinergicity of, 505–507 624 226 contextual fear, 618 Lysosomal outer membranes, 609 Melanin-concentrating hormone kinds/components of, 504–505 Lysozomal receptor degradation, (MCH), 192 methodology of, 500–504 182 Membrane(s), 613 muscarinic/atropinic drugs/ axonal plasma, 368 antiChEs, 507–510 M basement, 331 nicotinics/nicotinolytics, mAChRs. See Muscarinic colocalization, 613 510–511 acetylcholine receptors electroplaque, 157 today’s state of, 515 Macromolecules, 113, 332 lysosomal outer, 609 LEF. See Lymphoid enhancer MAG. See Myelin-associated mitochondrial, 86 factor glycoprotein postsynaptic, 46–47 Lesions Magnocellular nucleus, 61 pre-synaptic plasma, 41 forebrain, 364 Magnocellular preoptic area, 57 protein complex, 616–617 glutaminergic, 463 Main immunogenic region (MIR), Memorization, 512 hippocampal, 358, 422 210, 220 Memory, 500–515 Lidocaine, 443 Mammalian , amyloid effects/mutation of Ligand binding, structural 117 APP/PS1, 618 determinants of, 177–178 Mammalian muscarinic associative facilitation, 513 Ligands, 166, 168, 171, 177–178, acetylcholine receptors, 169 cholinergic/anticholinergic 192 Mammalian neuromyal junction, action mechanisms on, allosterically potentiating, 455 124 511–515 bivalent receptor, 166 MAP-2-enriched cholinoreceptive cholinergicity of, 505–507 stabilizing by, 180 cells, 528 desynchronization for, 513 Limb refl ex, 413 MAP-2-mediated microtubular engrams, 512 Lipids coherence, 529 hypotheses concerning, 513 bilayer, 216 MAPK. See Mitogen-activated kinds/components of, 504–505 choline containing, 83 protein kinase pathways methodology of, 500–504 Lipoprotein, 102 Marked plasticity, 353–354 muscarinic/atropinic drugs/ Locomotion, 191 Marsupial opossum, 336 antiChEs, 507–510 Locus coeruleus, 57, 443 Maze bright rats, 424 nicotinics/nicotinolytics, Loewi, O., 1, 2, 7, 9, 15, 240, 412, Maze dull rats, 424 510–511 415, 417 McGeer, Edith, 14 retrieval/encoding/consolidation, Long-term enhancement (LTE), medial forebrain system of, 514 512 57–58 short-term/working, 513 Long-term potentiation (LTP), 186, motor nuclei, 60 synapses, 425 436, 489, 512 parabrachial complex of, 58–59 today’s state of, 515 Lou Gehrig’s disease, 287 reticular system, 59–60 Memory/conditioning tests, 502 Low-affi nity carrier system striatal interneurons, 60 Meningeal vasculature, 605 (LAUS), 108 McGeer, P.L., 55–65 Meningoencephalitis, 636 Low-affi nity choline uptake, medial forebrain system of, Mental functions, 456 108–109 57–58 Mental phenomena, 455 blood-brain barrier transport of motor nuclei, 60 mEPCs. See Miniature endplate choline and, 108–109 parabrachial complex of, 58–59 currents sharing of two uptake systems, reticular system, 59–60 MEPPs. See Miniature endplate 108 striatal interneurons, 60 potentials Low-affi nity receptor, 353 MCH. See Melanin-concentrating Mestinon, 247 Low-density lipoprotein (LDL)- hormone Mesulam, M.M., 65–68 receptor-mediated Mechanoelectrical transduction, Metabolic potentiation of toxicity, mechanism, 611 499 271–272 Index 679

Metabolics, 85 Morphogenetic actions, 378 G proteins, 183–190 Metabolism Morphogenetic phenomena, 287 ion channels, 186–190 of ACh, 81–131, 411, 659 Morphogens, cholinergic receptor dimerization/ amyloid, 634 components as, 317–319 oligomerization, 188–190 of antiChE, 267–272 Morphologic hyperplasia, 346 Muscarinic agonists, 164–168, of central cholinergic Motoneuron, 13, 329–332 423 transmission, 16–18 inhibitory pathways of, 420 Muscarinic antagonists, 509 of choline, 82, 90 karyotic, 330 Muscarinic cholinergic receptors, fat, 102 Motor coordination, 190 154, 628–629 glucose, 471 Motor functions, 461–464 abstract phase of, 154–156 neuronal, 346 Motor neuron disease (MTD), 602 cholinergic transmission and, of organophosphorus Motor proteins, 54 154 anticholinesterases, Mouse city, 503 muscarinic/enzymes/bacteria, 267–272 MTD. See Motor neuron disease 151–153 Metalloproteinase, 224 Multiarm mazes, 502 reality of, 156–157 Methacholine, 123 Multifactorial phenomena, 468 research history of, 151–159 Methadone, 516 Multiple kinases, 625 Muscarinic cholinomimetics, 419 Methyllcaconitine (MLA), 446 Muscarine, 7 Muscarinic desynchronization, 479 , 260 Muscarinic, 151–153 Muscarinic drugs, 507–510 Mice Muscarinic acetylcholine receptors Muscarinic receptor subtypes, 176 knockin, 226–228 (mAChRs), 163–193 Muscarinic receptors, 153 knockout, 190–193, 214, agonists of, 164–168, 423 in cerebellum, 324 226–228 allosteric modulators for, in CNS, 427 Microdialysis technique, 438 170–173 subtypes of, 21, 176, 435 Microelectrodes, 4 antagonists for, 168–170, 509 Muscle hypoplasia, 379 Microiontophoresis, 433 in central nervous system, Mutagenesis, 114 Micropipettes, 4 163–193 , 110, 221, 249 Microtubules, 89 molecular biology of, Myelin-associated glycoprotein Midbrain reticular formation, 478 175–182 (MAG), 367 Milk ejection refl ex, 465 pharmacological classifi cation, Myoneural junction, 329–332, 420 Mind-body dilemma, 527 163–173 Myosincholinesterase, 126 Miniature endplate currents signaling pathways, 183–190 Myotubular cholinergic receptors, (mEPCs), 50 extensive homology modeling 330 Miniature endplate potentials of, 178 (MEPPs), 50, 441 ion channels, 186–190 N MIR. See Main immunogenic calcium channels, 187–188 N-acetyl neuraminic acid (NeuAc), region chloride channels, 188 367 Mitochondria, 86 potassium channels, 186–187 nAChR. See Nicotinic Mitochondrial acetyl coenzyme, knockout mice for functional acetylcholine receptors 89 insights from, 190–193 nAChR protein, 215–217 Mitochondrial membrane, 86 ligand binding structural NADPH. See Nicotinamide Mitogen-activated protein kinase determinants for, 177–178 adenine, dinucleotide pathways (MAPK), localization/distribution of, phosphate 185–186 173–175 Naloxone, 498, 517 MLA. See Methyllcaconitine mammalian, 169 Nascent polypeptide chains, 124 Modulating membrane fl uidity, molecular biology of, 175–182 National Institute of Neurological 613 receptor subtypes of, 175–177 and Communicative Molecule, protoplasmic, 152 phylogenetic tree for, 176 Disorders and Stroke and Mollusk glia, 215 posttraditional modifi cation/ the Alzheimer’s Disease Monoamine game, 23, 425, 486 receptor regulation, and Related Disorders Monoamine transmitters, 448 180–182 Association (NINCDS- Monooxygenases, 269 receptor activation/G protein ADRA), 633 Monosynaptic fl exor, 457 coupling, structural National Institutes of Health (NIH), Morphine, 251, 443, 495, 496 determinant of, 179–180 286 Morphinoids, 496 signaling pathways Natural ovulation cycle, 467 Morphogenesis, 375 enzymes, 184–186 Naxolone-induced withdrawal, 517 680 Index

NBM. See Nucleus basalis characteristics/functions of, structures of, 211–220 magnocellularis; Nucleus 345–361 Neuronal perikarya, 47 basalis of Meynert neurogenesis of, 353–359 Neuronal tissues, 104–107 N-dimethyl carbamate, 249 Nervous system, 1. See also Neuroprotective agents, 637 Neocortex, 335, 514 Central cholinergic nervous Neurotactin, 130 Neonicotinoid agonist insecticides, system; Central nervous Neurotensin-evoked depolarization, 217 system; Cholinergic 452 Neophilia, 504 pathways Neurotoxic esterase (NTE), 284, , 379, 470 NeuAc. See N-acetyl neuraminic 285 Neostratium, 359 acid Neurotoxicity, OP-induced Nerve cells, 420 Neural crest cells, 327 delayed, 278–285 Nerve growth factor (NGF), 67, Neurite growth, 291 Neurotoxins, 503 340, 341–361, 343, 628– Neurocellular proteins, 602–605 clostridial, 46 629, 657 Neurodegenerative diseases, Neurotrophic factors, 350 anti, 358 603–604 Neurotrophin p75 receptor, 601 Aβ regulated by, 629–630 Neurogenesis, 126, 319–335, 320– Neurotrophins, 361–362 characteristics/functions of, 325, 332–334, 365–367 anterograde-wise-acting, 368 345–361 avian, 322 targets, 361 further fi ndings concerning cholinergic, in sensory brain Neurotropism, 348 central NGF/NGF receptors, areas, 325–326 NGF. See Nerve growth factor 349–352 of NGF, 353–359 NGF protein, 67 high-affi nity receptors, nonneurotrophic elements, NGF receptors, 349–352 352–353 365–367 N-glycosylation, 181 low-affi nity receptor, 353 postnatal, 335–338 Nicotinamide adenine, dinucleotide nerve growth factor action on rodent, 321 phosphate (NADPH), 269 sympathetic ganglia/sensory Neurogenetic appearance, Nicotine, 152 neurons, 345–349 319–320 actions, 154 neurogenesis of, 353–359 Neurohypophysial hormones, 423 addiction, 520–521 context of, 357 Neurokines, 362–364 early studies of, 413–415 denervation and, 371 Neuromuscular basal lamina, 116 effects, 223–224 discovery/early concepts/non-NGF Neuromuscular blocker high sensitivity, 226 trophic factors, 341–343 alcuronium, 170 induced upregulation, 223 early story of other retrophins/ , 330 seeking behavior, 520 trophic substances, 343–345 Neuromyal junction, 51, 124, 339 Nicotinic acetylcholine receptors endogenous, 347 Neuron(s). See also Cholinergic (nAChR), 209 loop domains of, 351 neurons functional roles of, 221–228 protein, 67 autonomic ganglia, 214 central nAChRs, 222–223 receptors, 349–352 basal forebrain cholinergic, 188 ganglionic AChRs, 221–222 regenerative capacity of, 360 cerebral Purkinje, 437 genetic approaches to regional distribution of, 354 cholinergic basal forebrain, 505 understanding physiological retrophic factors of, 361–370 cholinergic spinal, 457 roles of, 224–228 gangliosides, 367–369 cholinoreceptive, 426, 456–457 neuronal AChRs in growth factors acting on dopaminergic, 226 nonneuronal tissues, 224 nervous system, 364–365 glutaminergic, 451 nicotine effects, 223–224 neurokines/ciliary invertebrate, 50 skeletal muscle α1 nAChRs, neurotrophic factor, in monkeys/rats, 66 221–222 362–364 programmed death of, 355 heteromeric neuronal, 214 neurotrophins, 361–362 spiny projection, 191 mice effected by, in knockouts/ nonneurotrophic elements supernumerary, 355 knockins, 226–228 concerned with variations in, 65 structures of, 211–220, 215–220 neurogenesis/ Neuronal AChRs, 224–226 ACh binding site, 217–218 synaptogenesis, 365–367 Neuronal homologues, 210 arrangement of AChR signaling at synapse of, 344 Neuronal metabolism, 346 subunits, 217 target innervation and, 372 Neuronal nicotinic receptors cation channel, 218–219 Nerve growth factor receptors, functional roles of, 221–228 large cytoplasmic domain, 347 history of, 209–211 220 Index 681

main immunogenic region, Noncholinergic vesicles, 44 OP-induced delayed neuropathy 220 Noncholinoreceptive cells, 427 (OPIDN), 267, 279, 281 shape of nAChR protein, Nonnervous tissues, 14 characteristics of type I/type II, 215–217 Nonneuronal tissues, 224, 369 283 subtypes of, 212 Nonneurotrophic elements, treatment of toxicity of, 290 Torpedo electric organ structure 365–367 Operation Desert Storm (ODS), of, 219 Non-OP antiChEs toxicity 285–287 in unusual forms of synaptic treatment, 290 Opiate(s), 453 transmission, 223 Nonselective cation treatment, 209 addiction, 516–517 Nicotinic agonists, 477 Norepinephrine, 347, 429 mechanisms, 498 Nicotinic autoreceptors, 430 Normal/lithium inhibited receptors, 443 Nicotinic blasters, 457 echinoderm development, OP-induced delayed neurotoxicity, Nicotinic cholinergic receptors 315 278–285 abstract phase of, 154–156 NTE. See Neurotoxic esterase Opioid(s), 495 cholinergic transmission and, Nucleus endogenous, 498 154 accumbens, 174 Opioid cholinergic interaction, muscarinic/enzymes/bacteria, basalis, 335, 368 498 151–153 cuneiforms, 497 Organogenesis, 317, 319–335, reality of, 156–157 interpeduncularis, 57 332–334 research history of, 151–159 magnocellular, 61 Organophosphorus (OP), 10, 111. Nicotinic postsynaptic receptors, raphe magnus, 406 See also OP drugs 428 retiularis dorsalis, 469 agents, 243–244 Nicotinic presynaptic Nucleus basalis magnocellularis compounds of, 259 autoreceptors, 441 (NBM), 13, 37, 57, 355, inhibition of, by agents of, Nicotinic receptors, 157, 324, 331 502, 506, 600 261–262 cholinergic, 330 Nucleus basalis of Meynert Organophosphorus rodent, 336 (NBM), 481, 632 anticholinesterases, 243, Nicotinics, cognition/learning/ 244 memory and, 510–511 O acute toxicity of, 273–276 Nicotinolytics, 465 Oblivion, 597 detoxifi cation of, 267–271 cognition/learning/memory and, Offensive aggression, 495 mechanism of activation/ 510–511 Olfactory bulb, 57 reactivation of Nigrostriatal radiations, 428 Olfactory tubercle, 174 phosphorylated enzyme, NIH. See National Institutes of Oligomeric receptor complex, 189 261–262 Health Oligomerization, 188–190 inhibition of AChe by OP NINCDS-ADRA. See National Oligomers, 119 agents, 261–262 Institute of Neurological Olivocochlear, 431 phosphorylated AChe aging, and Communicative Olivocochlear bundle, 499 262–263 Disorders and Stroke and Ontogency, 338–339 rate of aging, 263 the Alzheimer’s Disease Ontogenesis, 48, 367 reactivation of phosphorylated and Related Disorders AChE in, 320 AChE, 263–265 Association general scheme of participation metabolism/detoxifi cation of, Nitric oxide (NO), 185, 425 of neurotransmitters in, 322 267–272 Nitric oxide synthase (NOS), 185 Ontogenetic effects, 377–380 metabolic activation, 271 N-methyl-D-aspartate (NMDA), Ontogeny, 14 metabolic potentiation of 369, 636 Oocytic cholinergic receptor, 318 toxicity, 271–272 NO. See Nitric oxide OP. See Organophosphorus structure-activity/bonding, Noncholinergic cells, 48–49, 86, OP drugs, 242–246 260–261 91, 429 antiChEs and, 242–246 Orthosteric ligand, 171 Noncholinergic pharmacology, chronic toxicity of, 276–278 Orthosteric ligand kinetics, 178 440–455 neurotoxicity of, 278–285 Other behaviors, 621–625 postsynaptic, 449–451 treatment of, 288–290 Other tissues, 104 presynaptic, 443–444 animal experimentation, 289 Ovicides, 378 Noncholinergic presynaptic human experience, 289–290 Oxepin, 635 terminals, 431 OPIDN toxicity, 290. See OP- Oxidation, 260 Noncholinergic systems, 453 induced delayed neuropathy Oxime reactivators, 156 682 Index

Oximes Pharmacology Phosphorylation active, 245 cholinergic pre/postsynaptic, in AD, 619 mono/biquaternary, 245 440–443 agonist-dependent, 182 phosphorylated, 265 noncholinergic, 440–455 receptor, 182 Oxotremorine, 156, 165, 166 orthodox, 442 stechiometric, 261 Oxytocin, 464 postsynaptic noncholinergic, Phosphotriesterases (PTEs), 269 449–451 Photomicrographs, 337 P presynaptic cholinergic, 440–441 Phylogenesis Pacinian corpuscles, 124 Phenomena, 370–377 of cholinergic systems, 339–340 PAD. See Primary afferent biochemical, 453, 454 immediate concerns with, depolarization cardiovascular controlled, 658–659 Pageant of physostigma, 237–242 468–471 Phylogenetic cholinergic research, Paired helical fi laments (PHF), cholinergic EEG, 17 14 602, 618 controlling nicotinic receptors, Phylogenetic distribution, 339 Pallidothalamic relays, 463 331 Phylogenetic omnipresence, 126 Parabrachial complex, 58–59 divorce, 525 Physostigma venenosum, 237 Paradoxical sleep, 487 hypersynchrony, 490 , 7, 240, 246, 379, Parasympathetic sites, 10 mental, 455 413–415 Paraventricular nuclei, 464 morphogenetic, 287 Physostigmine atropine Parkinson’s disease, 193, 370, 522 multifactorial, 468 antagonism, 413 Parsimonious axonal growth, 340 proliferative, 360 PI. See Phosphoinositide Parsimony, 115 respiratory, 459 Pilocarpine, 165, 413 Particulate neuron matter, 85 Phenothiazines, 97 Pilocarpine-induced seizure, 506 Pathway maps, 61–65 , 247 Pineal organ, 464 Pathways. See also Cholinergic Phenyl carbamates, 248 Piperdines, 250 pathways; Signaling Phenyl sulfonyl fl uorides, 251 Piperidine heterocyclic agents, pathways Phenylmethylsulfonyl fl uoride 249 ascending cholinergic, 64 (PMSF), 253, 284 Pirenzepine, 158 catecholaminergic, 463 PHF. See Paired helical fi laments PKC. See Protein kinase C central cholinergic, 412 PHF-tau. See Phosphorylated tau Placca motrice, 153 central nervous, 421 Phosphatidylcholine, 91, 93, 101 Placental syncytium, 129 diagonal band, 449 as ACh precursor, 96–100 Plasmalemma, 52, 617 MAPK, 185–186 blood, 94 fusion, 54 septo-hippocampal, 369 as phospholipid precursor, postsynaptic, 331 visual, 56 96–100 terminal, 44 WNT/GSK3β/β-Catenin/E- Phosphatidylethanolamine, 91 Plasticity, 512 cadherin, 622–626 Phosphatidylinositol cascade, 435 Platelet-derived growth factor PDE. See Phosphodiesterase Phosphatidylinositol-specifi c (PDGF), 365 PDGF. See Platelet-derived growth phosphates C (PIPLC), 262 PLC. See Phospholipase C factor Phosphodiesterase (PDE), 184 PMSF. See Phenylmethylsulfonyl Peptidergic systems, 471 Phosphoinositide (PI), 180 fl uoride Peripheral cholinergic disease, Phospholipase C (PLC), 318 PNS. See Peripheral nervous 481 Phospholipases, 184–186 system Peripheral muscarinic intoxication, Phospholipid hydrolysis, 95 Polyneuritis, 280 275 Phospholipid precursor, 96–100 Polyspermy, 318 Peripheral nervous system (PNS), Phospholipids, 91–93, 93–95 Pontogeniculate occipital (PGO), 627 brain, 91–93 483, 485 Peripheral nicotinic intoxication, choline/phosphatidylcholine as Pontomesencephalic formation, 275 precursor to, 96–100 59 Pertinent circuitry, 459 Phospholipids-choline cycle, 95 Positively charged nitron, 172 Pertinent nuclei, 56 Phosphoryl choline, 92, 265 Positron-emission tomography Pertinent photomicrographs, 42 Phosphorylated AChE, 263–265 (PET), 111 PET. See Positron-emission Phosphorylated choline, 91 micro-, 600 tomography Phosphorylated enzyme, 261–262 Post-Ecclesian cholinergic studies, PFF. See Propentofylline Phosphorylated oximes, 265 422–426 PGO. See Pontogeniculate occipital Phosphorylated tau (PHF-tau), 620 Postnatal neurogenesis, 335–338 Index 683

Postreinforcement synchronization active, 334 R (PRS), 477 basic globular, 85 RAB protein, 45 Postsynaptic cholinergic response, collapsing response mediator, Radiations 50 619 homogenous, 427 Postsynaptic cholinoreceptivity, expressed receptor, 173 nigrostriatal, 428 427–429 extracellular-signal regulating Radioactive decamethonium, Postsynaptic differentiation, 374 kinase-mitogen-activated, 157 Postsynaptic enzyme, 36 510 Radioligand binding, 168, 192 Postsynaptic membranes, 46–47 G-coupling, 164, 179–181, Raphe magnus nucleus, 406 Postsynaptic modulation, 454 183–184 Rapid eye movement (REM), 19, Postsynaptic neurotransmitter glyco, 330, 366 411, 484 interaction, 451–452 lipo, 102 Rapsyn, 331, 366 Postsynaptic noncholinergic low-molecular-weight Rats, 66 pharmacology, 449–451 microtubule-associated- maze bright, 424 Postsynaptic plasmalemma, 331 weight, 618 maze dull, 424 Postsynaptic responses, 49–52 MAPK, 185–186 RBC. See Red blood cell Potassium channels, 186–187 membrane complex, 616–617 Receptology Preneurogenesis stages, 48 motor, 54 cholinergic, 4 Preneurogenetic ontogenesis, 324 Myelin-associated glyco, 367 immediate concerns with, 660 Preponderant cholinergic NAChR, 215–217 Receptor(s), 166, 181, 332, 509, correlates, 69 neurocellular, 602–605 611. See also Acetylcholine Presenilin, 622–626, 626 NGF, 67 receptors; Muscarinic E-cadherin/β-catenin pathway SNAPs, 52 cholinergic receptors; and, 625 structural noncatalytic, 112 Nicotinic cholinergic mutations, 617–618, 631 trimeric scaffold, 182 receptors; Nicotinic WNT/GSK pathway and, very low density lipo, 102 receptors 624–625 Protein kinase C (PKC), 181, 608, auto, 429–431 Presynaptic cholinergic 615 bivalent, 166 pharmacology, 440–441 Proteolytic analysis, 351 bivalent, ligands, 166 Presynaptic cholinergic receptor Proteolytic cleavage, 608–609 chemo, 460 responses, 49 Proteus vulgaris, 271 cholinergic, 46–47, 151–159, Presynaptic cholinoreceptivity, Protochordate amphioxus, 122 321 429–431, 430 Protoplasmic molecule, 152 cholinergic nicotinic, 330 Presynaptic enzyme, 36, 128 Prototypical modulators, 178 GPCR, 163, 623 Presynaptic noncholinergic PRS. See Postreinforcement hetero, 430, 445, 457 pharmacology, 443–444 synchronization high-affi nity, 352–353 Pre-synaptic plasma membrane Pseudomonas, 270 low-affi nity, 353 (PSPM), 41 Pseudomonas diminuta, 271 lysosomal, degradation, 182 Presynaptic transmitter interactions, PSPM. See Pre-synaptic plasma mammalian muscarinic 444–449 membrane acetylcholine, 169 Prevertebrate amphioxus, 120 Psychological functions, 456 muscarinic, subtypes, 21 Primary afferent depolarization PTEs. See Phosphotriesterases myotubular cholinergic, 330 (PAD), 457 Pulmonary gas exchange, 280 neurotropin p75, 601 Programmed cell death, 349 Purkinje cell, 36 NGF, 349–352 Programmed neuronal death, 355 Push-pull cannula, 422, 438 nicotinic, 157, 324, 330, 331, Prolactin, 466 Pyrexia, 474 336 Proliferative phenomena, 360 Pyrrolidine ring, 246 nicotinic auto, 430 Proline-rich-attachment-domain Pyrrolidinecholine, 47 nicotinic postsynaptic, 428 (PRAD), 116, 120 Pyruvate, 86 nicotinic presynaptic auto, 441 Propentofylline (PFF), 620 oocytic cholinergic, 318 Prophylaxis, 288–290 Q opiate, 443 Propylbenzilcholine mustard, 177 Quantitative structure-activity phenomenon controlling Prostaglandins, 472 relationship (QSAR), 660 nicotinic, 331 Protein, 54. See also Low- Quaternary ammonium groupings, rodent nicotinic, 336 molecular-weight 152 trk, 353 microtubule-associated-weight Quaternary curarimimetics, 420 Wild-type, 179 684 Index

Receptor activation, 179–180 Reticular activating system, 35 SER. See Smooth endoplasmic Receptor defi cient knockout mice, Reticular system, 59–60 reticulum 509 Retina, 42 Serine, 121 Receptor desensitization, 436 cholinergic cells in, 61 Serotonergic agonists, 494 Receptor dimerization, 188–190 cholinergic maturation of, 312 Serotonin, 445 Receptor phosphorylation, 182 Retrograde discharge, 24 Several brain structures, 448 Receptor regulation, 180–182 Retrophic factors Sexual behavior, 475–477 Receptor subtypes, 4 neurokines/ciliary neurotrophic Sexual pleasure stimulus, 476 Receptor subtype-specifi c factor, 362–364 Shallow input memory, 504 electrophysiological neurotrophins, 361–362 Short-lived amnetic action, 505 postsynaptic responses, 442 Rett syndrome, 503 Sialic acid-containing Reciprocal neurotransmitter Reward punishment dipole, 514 glycoshingolipids, 367 interactions, 454 Rhinecephalon, 500 Signaling pathways Recombinant expression systems, Rodent forebrain, 335 enzymes, 184–186 164 Rodent neurogenesis, 321 phospholipases, 184–186 Recycling processes, 44 Rodent nicotinic receptors, 336 G proteins, 183–184 Red blood cell (RBC), 100, Rostral hypothalamus, 473 ion channels, 186–190 107–108 calcium channels, 187–188 Reductionism, 525–529 S chloride channels, 188 Reductionistic naivete, 424 Salivation, lachrymation, urination, potassium channels, 186– Refl ex defecation (SLUD), 522 187 limb, 413 Salmonella, 271 Single genetic locus, 611 milk ejection, 465 SAR. See Structure activity Single spike potential, 458 Refl exogenic action, 456–459 relationship Size-izomers, 116 Release processes, 48 SCG. See Superior cervical Skeletal muscle α1 nAChRs, REM. See Rapid eye movement ganglion 221–222 REM sleep-linked partial muscular Schizoid behavior, 523 Skeletal muscle preparations, 155 atonia, 460 Schizophrenia, 522, 525 Skeletal neuromuscular disorder, Renshaw cell, 13, 415 Schwann cells, 369 210 depressed amino acid-induced Scopolamine, 460, 462, 486 Sleep, 477–491 excitation, 449 SDHACU. See Sodium-dependent- awakening of arousal/sleep experiment, 419 high-affi nity choline uptake phases/cholinergic agonists/ stimulation, 419 α-secretase, 614–615 antagonists, 483–487 Renshaw circuitry, 439 β-secretase, 615–616 central nervous system seizures/ Renshaw interneurons, 434 γ-secretase, 616–618 cholinergic system, Representative reactivators, 264 localization of activity of, 616 487–490 Reserve pool, 47 membrane protein complex of, chronobiology, 490–491 Respiration, 459 616–617 EEG patterns/evoked potentials/ Respiratory phenomena, 459 presenilin mutations of, 617–618 cholinergic agonists/ Responses Secreted APP, 610–611 antagonists effects, blood fl ow, 470 Secretion competence factors, 52 477–483 central excitatory muscarinic, Seizures, 506 endogenous activity of 431–436 generation, 489 cholinergic neurons, 477 central excitatory nicotinic, pilocarpine-induced, 506 paradoxical, 487 431–436 Selected dissociation constants, phases, 483–487 central inhibitory postsynaptic 169 slow, 486 cholinoceptive, 436–437 Self-collapse, 529 theta rhythm, 479–481 cholinoreceptive, 426–437 Sematostatin, 474 Slow sleep, 486 intra-oocytic, 316 Sensorium, 499–500 SLUD. See Salivation, postsynaptic, 49–52 Sensory brain areas, 326 lachrymation, urination, postsynaptic cholinergic, 50 Sensory ganglia, 345–349 defecation presynaptic cholinergic receptor, Sensory innervation, 350 Smooth endoplasmic reticulum 49 Sensory-motor gatting, 190 (SER), 281 receptor subtype-specifi c Septal cell line, 467 SNAPs. See Soluble N- electrophysiological Septo-hippocampal pathways, ethylmaleimide attachment postsynaptic, 442 369 proteins Index 685

Sodium-dependent-high-affi nity memory, 425 Terminal plasmalemma, 44 choline uptake (SDHACU), of NGF, 344 (TEPP), 105–107 Synapsin, 331 23, 242, 279, 450 Soluble extracellular domain, 615 Synaptic cytodifferentiation, 336 , 24, 217 Soluble N-ethylmaleimide Synaptic markers, 43 Tetrahydro-5-aminoacridine attachment proteins Synaptic strength, 504 (THA), 242, 601 (SNAPs), 52 Synaptic transmission, 24, 54 Tetrahydroaminoacridine, 632 Sphingomyelin, 101 Synaptic vesicles, 43, 47, 50 Tetrahymena gelii, 311 Spinal cholinoreceptive cell, 457 cycling/recycling of, 47 Tetralogic actions, cholinergic Spinal motoneuron survival, 363 Synaptogenesis, 319, 325, 326–332 components and, 378– Spiny projection neurons, 191 autonomic ganglia, 327–329 380 Splicing, 85 central, 332–334 Tetralogic effects, 377–380 Spring, 45 heart and, 326–327 Tetralogy, cholinergic, 290–291, SREBPs. See Sterol regulatory increased cortical, 358 314 element-binding motoneuron/myoneural junction, Tetramers, 118 Stechiometric phosphorylation, 261 329–332 THA. See Sterling Winthrop Research nonneurotrophic elements, Tetrahydro-5-aminoacridine Institute, 252 365–367 Thalamic simulation, 482 Sterol regulatory element-binding Synaptogens, 371–377 Thalamocortex, 335 (SREBPs), 616 Synaptosomes, 41 Thalamus, 128 Stoichiometries, 214 Synchronized EEG potentials, Thermocontrol, 455, 471–473 Striatal interneurons, 60 481–482 Thermoregulation, 163 Striatum, 191 Synchronized patterns, 482–483 Theta rhythm, 479–481 Structural noncatalytic proteins, Syndrome(s) hippocampal, 523 112 aversive, 463 with learning processes, 480 Structure activity relationship CMS, 224–225 Theta waves, 480 (SAR), 152, 252–256 down, 614 Thiamine, 266 Structure-activity, of Gulf War, 272, 278–287 Thirst/hunger control, 473–474 organophosphorus megacystis-microcolon-intestinal Thirst/hunger regulation, 474 anticholinesterases, hypoperistalsis, 226 Throphotrope, 425 260–261 Rett, 503 Thyrotropin-releasing factor (TLF), , 266, 488 rett, 503 466 Strychnine-induced convulsions, Wernicke-Korsakoff, 519 Thyrotropin-releasing hormone 488 (TRH), 445 Strychnos toxifera, 151 T Tissues, 48–49, 92, 104–107, Submandibular gland, 371 , 255 437–440 Submaxillary gland, 127 Target innervation, 372 nonnervous, 14 Substantia innominata, 469 Tau biology nonneuronal, 224–226, 369 Substrates, 85 amyloid biology linked to in other, 104 Succinylcholine, 24, 111 Alzheimer’s disease, Tonic immobility, 495 Suckling refl ex, 465 597–638 Torpedo californica, 210 Sucrose-gap arrangement, 458 dysregulated processing of Torpedo differential splicing, Superior cervical ganglion (SCG), neurocellular proteins, 117 187 602–605 Torpedo electric organ AChe Superior olivary complex, 61 pathology of, 618–622 (TcAChe), 219, 253 Supernumerary neurons, 355 tau isoforms/phosphorylation in Toserin, 247 Suraspinal cholinergic function, AD, 619 Toxicity 471 glycogen synthase kinase 3β, cholinergic, 273–285 Sympathetic autonomic ganglia, 619–621 delayed cognitive, 273 432 Tau interactions, 630–631 delayed pulmonary, 278–285 Sympathetic ganglia, 10, 345– TcAChe. See Torpedo electric Tranquilizers, 444, 522 349 organ AChe Transferases, 270 Synapses T-cell factor (TCF), 624 Trans-Golgi network, 615 allergic inhibitory, 488 TCF. See T-cell factor Transient cell transfection analysis, cholinergic, 36, 424, 426 TEPP. See Tetraethyl 85 inhibitory, 488 pyrophosphate Transmethylation, 91 686 Index

Transmission. See also Cholinergic Trophic/growth factors, 340–341 Vesicle heterogeneity, 47 transmission Trypanosoma, 127 Vesicles, 44–45 central chemical, 417 Trypanosoma rhodesiense, 311 noncholinergic, 44 central cholinergic, 16–21, 415– Trypanosomes, 153 synaptic, 47 421, 440 Tryptophan amphiphilic Vesicular acetylcholine transport chemical, 11 tetramerization, 120 (VAChT), 332 dopaminergic, 522 d-Tubocuarine (d-TC), 432 Vesicular uptake, 17 electric, 416 Tubular blockers, 89 Visual cortical areas, 56 ganglionic, 24, 227 Tyrosine hydroxylase, 98 Visual pathways, 56 synaptic, 24 Tyrosine residues, 352 Voltage clamp methods, 4 Transmitter interactions, 38, VTA. See Ventral tegmental area 443–445 U postsynaptic neuro-, 451–452 Unaggregated peptide, 606 W presynaptic, 444–449 Upper brainstem, cholinergic War gases, 237–292 Transmitters, 454 projections of, 66 Wellcome trust, 8 amino acid, 453 Upregulation, 233 Wernicke-Korsakoff syndrome, chemical, 420 Urinary activity, 471 519 false, 47–48 WHO. See World Health inhibitory, 435 Organization monoamine, 448 V WIld-type receptor, 179 Transport systems, 104–108 VAChT. See Vesicular WNT/GSK3β/β-Catenin/ Transsynaptic effects, 371–377 acetylcholine transport E-cadherin pathways, Transsynaptic regulation, 372 Vagotomy, 467 622–626 TRH. See Thyrotropin-releasing Varicosities, 336 Woolf-Butcher pontomesencephalic hormone Vasodilation, 470 tegmental complex, 68. See Tricyclics, 635 Vasopressin, 445, 465 also Cholingeric pathways , 48 Ventral tegmental area (VTA), World Health Organization Trimeric scaffold protein, 182 192 (WHO), 245 Trimethyl ammonium, 113 Vertebrates, 14 Trk receptors, 353 Very low density lipoproteins, Trophic substances, 342–345, 102 X 343–345 , 17 Xerostomic action, 505 Color Plate 1

Figure 1-3. Peter Waser, Alex Karczmar, and George Koelle during the 1974 Symposium on Cholinergic Mechanisms in Boldern, Switzerland. 2 Color Plate

Figure 1-4. Superimposed note from Edith Heilbronn. From left to right: row 1 (seated): John Blass, George B. Koelle, Peter G. Waser, Donald J. Jenden, Israel Hanin, Frank C. MacIntosh, Alex Karczmar, Edith Heilbronn, Giancarlo Pepeu, Alan M. Goldberg; row 2: Victor J. Nickolson, Nae J. Dun, Stanley M. Parsons, Agneta Nordberg, Ezio Giacobini, B.V. Rama Sastry, Kathleen A. Sherman, Mario Marchi, Michael Stanley, Larry L. Butcher, Fiorella Casamenti, Tsung-Ming Shih, Herbert Ladinsky, Silvana Consolo, Kenneth L. Davis, Darwin L. Cheney, Janusz B. Suszkiw, Michael R. Kozlowski; row 3: Dean O. Smith, Steven H. Zeisel, Susan E. Robinson, Barbara Lerer, R. Jane Rylett, Rochelle D. Schwartz, Joan Heller-Brown, Marie-Louise Tjörnhammer, Britta Hedlund, David S. Janowsky, Natraj Sitaram, Linda M. Barilaro, Paul M. Salvaterra, Denise Sorisio, Elias Aizenman, Ileana Pepeu, Aurora V. Revuleta, Felicita Pedata, Clementina Bianchi, Lorenzo Beani, Henry G. Mautner; row 4: S. Craig Risch, Guillermo Pilar, E. Sylvester Vizi, Thomas J. Walsh, Sikander L. Katyal, Rob L. Polak, Roni E. Arbogast, Jean Massoulié, Denes Agoston, Brian Collier, Lynn Wecker, Bruce Howard, Richard S. Jope, Bernard Scatton, Matthew Clancy, Paul T. Carroll; row 5: William G. VanMeter, Michael Adler, Peter Kasa, Annica B. Dahlström, Gary E. Gibson, Peter C. Molenaar, Ingrid Nordgen, John D. Catravas, Judith Richter, David M. Bowen, Mark Watson, Renato Corradetti, Lorenza Eder-Colli, Marvin Lawson, Ing K. Ho, Jack C. Waymire; row 6: Paul L. Wood, Matthew N. Levy, Jean-Claude Maire, Frans Flentge, Richard Dahlbom, Pierre Etienne, George G. Bierkamper, Robert G. Struble, A.J. Vergroessen, Seana O’Reagan, Robert Manaranche, Maurice Israel, Yacov Ashani, Abraham Fisher, Steven Leventer, Alan G. Mallinger; row 7: Anders Undén, Edward F. Domino, William D. Blaker, Peteris Alberts, Johann Häggblad, Daniel L. Rickett, Sten-Magnus Aguilonius, Serge Mykita, Hans Selander, Oliver Brown, Henry Brezenoff, Sven-Åke Eckernäs, Frederick J. Ehlert, Björn Ringdahl, Volker Bigl, Duane Hilmas, Clark A. Briggs, Nicolas Morel; row 8: Bo Karlén, Michael J. Dowdall, John J. O’Neill, Heniz Kilbinger, Wolf-D. Dettbarn, Konrad J. Martin, Konrad Löeffelholz, Roy D. Schwarz, Jerry J. Buccafusco, Ernst Wulfert, Howard J. Colhoun, Paul Martin, Jack R. Cooper, Crister Larsson, Harry M. Geyer, Michael J. Pontecorvo, William E. Houston, Jurgen von Bredow, Yves Dunant. (From Hanin, 1986. Reprinted by permission of Kluwer Academic/Plenum Press.) Color Plate 3

Figure 1-7. U.J. (Jack) McMahon (left) and Rene Couteaux at the ISCM meeting in Arcachon, 1998. Jack McMahon is a prominent modern investigator of the ultra- structure of the neuromyal junction. (From the Author’s private collection.)

Figure 1-9. Chris (Kazmir) Krnjevic at the Symposium in Honor of A.G. Karczmar, Loyola Medical Center, Maywood, IL, 1986. 4 Color Plate

Figure 1-10. From left to right: row 1: Doctoressa Ileana Pepeu, Erminio Costa, Marion Allen-Karczmar (Swami Sharadananda) and Leda Hanin; row 2: Israel Hanin, Giancarlo Pepeu, Alex Karczmar. Erminio (Mimo) Costa is a prominent psychoneuropharmacologist and one of the founders of the College of Neuropsychopharmachology. He pioneered the research on the role of serotonin, GABA, and catecholamines. He also contributed to the concept and measurement of the turnover of acetylcholine.

Figure 1-11. Edith McGeer at the 1986 Symposium in Honor of A.G. Karczmar, Loyola Medical Center, Maywood, IL. Color Plate 5

Figure 1-12. Nobel Prize winner Rita Levi-Montalcini and Ezio Giacobini at a Vatican Symposium, 1990.

Figure 1-13. Hermona Soreq is a prominent scientist from the Hebrew University of Jerusalem. Soreq pioneered molecular studies of cholinesterases. Currently she studies stress-induced variants of acetylcholinesterase. 6 Color Plate

Figure 1-15. Vincenzo Longo and Alex Karcz- mar in Rome, 1978. Vincenzo Longo, from the Istituto Superiore di Sanità, is a preeminent EEG investigator. He related EEG events and evoked potentials to behavior and REM sleep.

Choline ACh PCh

SM

Phosphatidylcholine

Figure 3-3. Distribution of choline in brain tissue. (From Loeffelholz and Klein, 2004, with permission.) ACh = acetylcholine; PCh = phosphatidylcholine; SM = sphingomyelin. Color Plate 7

Figure 3-8. Ribbon diagram of the three-dimensional structure of TcAChE. The side chains of the catalytic triad and of key aromatic residues in the active-site forge are indicated as purple stick figures. Acetylcholine, manually docked in the active site, is represented as a space-filling model, with carbon atoms shown in yellow, oxygen atoms in red, and nitrogen in blue. The quaternary group of the ACh faces the indole of Trp84. (From Silman and Sussman, 2000, with permission.) 8 Color Plate

AChE

ACTIVE SITE GORGE

b7 b8 b6 b1 b b b3 5 9 b4

b2

a Figure 3-9. Three-dimensional structure of G2 AChE from Torpedo. The structure is represented in a ribbon diagram showing b strands (green) and a as helices (red). The active gorge is located above the central b sheet and the arrow marks the location of the active-site serine, Ser 200. (From Massoulie et al., 1993b. with permission.) Color Plate 9

Figure 7.2. The plant Physostigma venenosum Balforii. (From Karczmar et al., 1970.) 10 Color Plate

Activates Microglia Induces Induces iNOS, TNFa, IL-1b COX-2

Activates NFkB/p65 Induces NFkB Nuclear PGE2, ROS Translocation Binds to Glutamate p75NTR Release Promotes Ab Activates 42 Formation Binds to Caspase-3 nAchR(7) b Catalyzes Ab b [A +nAchR7] down- Formation A reguulates ERK/MAPK

Leads to Inhibition of Inhibits PKA CREB phosphorylation

Impairs Leads to Amyloidogenic Hippocampal LTP Synaptotoxicity Processing within Lipid Rafts [Sphingolipid- cholesterol microdomains] Behavioral Deficits

Figure 10-2. Major events of amyloidogenic vicious cycle include: (top) Aβ-induced activation of nuclear tran- scription factor-NFkB, which in turn activates the pro-inflammatory cytokines (TNFα, IL-1β, IFNγ), leading to subsequent induction of inflammatory molecules such as inducible nitric oxide (iNOS), cyclooxygenase 2 (COX-2), and prostaglandin E2 (PGE2). These inflammatory molecules produce reactive oxygen species (ROS), leading to oxidative damage. In addition, COX-2 and iNOS trigger further activation of NFkB. NFkB binds to the p65 subunit, translocates to the nuclear compartment, and promotes the formation of Aβ42. Besides being a part of this vicious cycle, all these inflammatory molecules have other detrimental effects on neurons and neuronal connections, thus participating in neurodegeneration and synaptic deficits in AD; (left) activation of caspase-3, which leads to apoptosis and simultaneously potentiates further Aβ generation; (bottom right) impairment of PKA- and ERK/CREB-signaling, leading to synaptic and LTP deficits in the hippocampus that result in impairment of memory and learning; (bottom left) cholesterol, lipid, and lipoprotein receptor interactions with Aβ. Color Plate 11

770

Figure 10-3. Schema showing proteolytic cleavage sites on the APP770 molecule and the different peptides result- ing from proteolytic cleavages: bar with diagonal lines, extracellular N-terminal APP fragment; solid bar between diagonal- and vertical-line bars, Aβ-segment; bar with vertical lines, intracellular C-terminal fragment; dashed arrow, β-secretase site (after residue 671); center arrow, α-secretase site (after residue 687); right arrow, γ-secretase site (after residues 710 or 712). Second horizontal line represents full-length Aβ 40/42/43. Third horizontal line represents p3 fragment. Fourth horizontal line (left) represents sAPPα fragment (N-terminal-687). Fourth horizontal line (right) represents carboxyterminal fragment (CTF). Bottom horizontal line represents sAPPβ fragment (N-terminal-671). Vertical bar represents the membrane-spanning segment, which comprises residues 700 to 723.

Wnt binds to transmembrane receptor Frizzleds (Fz)

(Wnt + Fz)

Promotes accumulation Activates disheveled-1 of β-Catenin (dvl-1)

Promotes nuclear β Recruits GSK-binding translocation of -Catenin protein

Upregulates GSK3β and other genes Binds to GSK3β

GSK3β complexes Disrupts interaction β-Catenin degraded with Axin, APC between GSK3β-Axin

PKA Aβ PKC Mutant PS Li + Represses Derepresses (phosphorylates) GSK3β β-Catenin stabilized (dephosphorylates) GSK3β

Inhibits phosphorylation Phosphorylates of Tau and Kinesin Tau and Kinesin

Figure 10-4. Schema showing GSK3β signaling involved in linking amyloid, tau, and kinesin biology. Signaling pathway in black indicates Wnt-GSK3β cascade under normal circumstances. Signaling events in lavender indicate dynamic balance between phosphorylation and dephosphorylation of tau under normal circumstances. Signaling events at bottom left indicate overactivation of GSK3β leading to overphosphorylation of tau and kinesin under abnormal conditions. Signaling events at bottom right indicate factors that attenuate overphosphorylation of tau and kinesin. 12 Color Plate

Figure 11-1. Distant peaks. (From Goodwin Ahlberg, 1998, with permission.)