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Synapses Synapses Are the Functional Connection Between Neurons and a Few Other Cells (Eg

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Synapses Synapses Are the Functional Connection Between Neurons and a Few Other Cells (Eg Synapses synapses are the functional connection between neurons and a few other cells (eg. muscles, glands) CNS: neuron neuron PNS: neuron neuron neuron muscle fiber [=neuromuscular junction] neuron gland [=neuroglandular junction] each neuron synapses with 1000 – 10,000 axonal terminals 10 Billion Neurons in NS 500 Trillion Synapses presynaptic neuron vs postsynaptic neuron two kinds of synapses: 1. electrical synapses 2. chemical synapses 1. Electrical Synapses very common in embryonic brain, much less common in adults; get replaced by chemical synapses cells are directly connected with each other cytoplasm is continuous impulses can go in either direction eg. brain: rapid stereotyped eye movements eg. rhythmic contractions of smooth muscle eg. intercalated discs of cardiac muscle chambers contract as single cells 2. Chemical Synapses most common kind of synapse actual gap or space between nerve cells one direction only (= unidirectional) prevents direct transmission of action potential 1 requires release of a chemical messenger =neurotransmitter What Happens at Chemical Synapse: 1. AP travels down axon of presynaptic neuron to axonal end bulb 2. AP causes Ca++ gates to open and Ca++ enters presynaptic neuron 3. Ca++ activates enzymes in axonal end bulb which stimulates exocytosis of neurotransmitter [synaptic vesicles move to surface of cell and release NT] 4. NT diffuses across synaptic cleft 5. NT binds to specific receptor molecules in membrane of postsynaptic neuron (dendrite or cell body) 6. causes chemical gates to open allowing some ions in can cause partial depolarization or hyperpolarization depending on gates 7. termination of NT occurs when: a. it is degraded by enzyme on postsynaptic neuron or in synapse b. it returns to presynaptic neuron and is reabsorbed c. or it diffuses away from synapse whole process takes 0.3 – 5.0 ms Kinds of Chemical Synapses Above is general idea of what happens at a synapse There are different kinds of chemical synapses: 1. excitatory produce EPSP’s 2. inhibitory produce IPSP’s 1. Excitatory Synapses NT binding causes partial depolarization of post synaptic membrane Na+ and K+ ions diffuse simultaneously in opposite directions but more Na+ in than K+ out depolarization produces EPSP’s 2 lasts only a few milliseconds then membrane returns to resting potential 2. Inhibitory Synapses NT binding induces hyperpolarization of membrane: becomes more permeable to K+ (out) and/or more permeable to Cl- (in) causes hyperpolarization produces IPSP’s Synaptic Interactions (Neural Circuits) Remember, each postsynaptic neuron may synapse with 10,000’s of presynaptic neurons (=neuronal pools) some of these synapses are excitatory; some are inhibitory sum of all EPSP’s and IPSP’s at a particular time determine whether a neuron will generate an action potential or not Summation: 1. Temporal summation 1 or more neurons transmit impulses in rapid sequence 2. Spatial summation large # of terminals are stimulated at the same time axonal hillock acts as a “bean counter” it totals all the effects may or may not trigger AP Potentiation: can also get potentiation (facilitation) doesn’t fire but easier to fire next time. Finally, there are literally 100’s of different kinds of neurotransmitters; some excitatory, some inhibitory bind to specific receptors in specific parts of nervous system can produce a variety of effects on post synaptic neurons 3 also can get various additional modifications of synapse: changes in the amount of NT released changes in excitability of post synaptic neuron presynaptic inhibition neuromodulation etc. Neurotransmitters neurotransmitters are the language of the nervous system NT are released at chemical synapses 100’s have been identified some are excitatory some are inhibitory the same NT may have different effects in different parts of body eg. excitatory one place, inhibitory another The effect of a NT on a postsynaptic neuron depends on the properties of the receptor not on the nature of the NT some neurons produce and release a single NT most make 2 or more and can release one or all synapses in PNS release only a few different neurotransmitters esp ACh, Epinephrine, NE most of the diversity is in the CNS, esp the brain a variety of different chemicals have been found to act as neurotransmitters: 1. acetylcholine 2. protein & amino acid derivatives biogenic amines amino acids peptides proteins 3. Inorganic gasses 4. ATP Effects of Drugs on Nervous Transmission 4 Drugs generally interfere with key steps in synaptic transmission: 1. affect NT synthesis 2. alter rate of release 3. prevent binding to receptor 4. prevent NT inactivation The end result of these actions: 1. drugs mimic specific neurotransmitters 2. enhance the actions of a NT 3. block action of NT 1. Drugs with general effects on Synapses a. Dilantin used to treat epilepsy epilepsy a too rapid firing of certain brain cells subsides only when NT supply runs out dilantin increases effectiveness of Na+ active transport to stabilize resting potential b. Caffeine stimulant generally lowers threshold at synapses 2. Acetylcholine (ACh) 1st to be identified at all NM jcts also found in autonomic NS at some smooth and cardiac muscles generally has stimulatory effect on skeletal muscles in autonomic NS may have stimulatory or inhibitory effect in CNS: 1. inadequate amt ACh correlated with Alzheimer’s 2. ACh receptors destroyed in Myasthenia gravis, an autoimmune disease in PNS: Acetylcholine at NM Jcts 1. Botulism Toxin blocks release of ACh paralysis 2. Black Widow Toxin stimulates massive releases of ACh intense cramping & spasms 3. Nicotine mimics ACh binds to receptor and activates it but no enzyme to remove it 5 prolonged hyper activity 4. atropine, curare binds to receptor but does not induce muscle contraction since ACh cannot bind to receptors already bound to curare muscle cells cannot be stimulated to contract paralysis in most synapses, once ACh binds to receptor and initiates a response it is removed by enzyme acetylcholinesterase nerve gas, malathion (=Cholinesterase inhibitors) blocks breakdown of ACh extended, extreme contractions 3. Protein & Amino Acid Derivatives broadly distributed in brain affect behavior, moods, sleep, thought some examples: a. dopamine a catecholamine synthesized from tyrosine esp in substantia nigra of basal ganglia (midbrain) affects coordination of skeletal muscles also a “feel good” NT 1. Parkinson’s Disease deficiency tremors (no inhibition of basal nuclei) 2. schizophrenia correlated with excess of dopamine 3. amphetamines enhance its feel good effects 4. cocaine blocks its uptake b. norepinephrin esp in brain stem another “feel good” NT affects mood: arousal, dreaming also released by some neurons in autonomic NS (sympathetic branch) 6 1. generally excess mania deficiency depression 2. Cocaine & amphetamines prevents inactivation of norepinephrin enhances its effect amphetamines and cocaine have similar effect as on dopamine c. serotonin indolamine syn from tryptophan or histidine in brain stem (reticular system) induces sleep, temp regulation, appetite, affects mood and aggression 1. LSD binds to serotonin receptors prevents its effect or counteracts its function in brainstem (RAS) 2. Prozac prevents its uptake relieves anxiety and depression 3. linked to migraine headaches d. histamine produced in hypothalamus in immune system is powerful vasodilator e. aspartate amino acid only in CNS excitatory f. glutamate amino acid only in CNS excitatory important in learning and memory 1. released in large quantities after stroke increases damage to nervous tissue g. glycine amino acid in spinal cord inhibitory 7 strychnine blocks receptors causes convulsions h. GABA modified amino acid most abundant inhibitory NT in brain (~1/3rd of all) inhibits skeletal movements 1. deficiency: Huntington’s disease jerky movements 2. alcohol enhances its inhibitory effects slowed reflexes reduced coordination also affects mood excess: less anxiety deficiency: more anxiety 1. Valium binds to GABA receptors mimics or enhances its effects less anxiety i. Substance P peptide (chain of amino acids) mediates pain transmission in PNS in CNS affects mood also involved in respiratory and cardiovascular control j. endorphins & enkephalins peptides in limbic system and related structures natural opiates reduces pain perception “runners high” 1. morphine, heroin, methadone binds to enkephalin receptors mimicks effecs of endorphins k. cholecystokinin peptide 8 may be related to feeding disorders 4. Inorganic Gasses a. NO (nitric oxide) toxic gas short lived is synthesized on demand not stored in axonal vesicles in CNS may be involved in learning and memory in PNS causes relaxation of smooth muscle b. CO (carbon monoxide) in CNS similar physiology as NO 5. ATP now recognized as a major neurotransmitter in both CNS and PNS produces fast excitatory response at certain receptors Neuromodulators other chemicals can be released at synapse in addition to neurotransmitters: =neuromodulators neuromodulators can influence the release of NTs or the post synaptic neuron’s response to the NT NM are usually peptides = neuropeptides a chemical may be both a NT and NM neuromodulators function in 3 different ways: 1. have direct effect on membrane potential by opening and closing chemical gates 2. have indirect effect on membrane potential thru “second messenger” eg. receptor on cm adenylate cyclase cyclic AMP 3. gasses are lipid soluble and diffuse into post-synaptic cell to activate enzymes and second messengers 9.
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