DOCSLIB.ORG

Neurotransmitter Receptors: Structure and Function

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neurotransmitter Receptors: Structure and Function Neurotransmitter receptors: Structure and function B. Bettler Institute of Physiology Basel March 30, 2010 Overview History Ionotropic receptors: - Structure and synaptic functions - Pathology Metabotropic receptors: - Structure and synaptic functions - New insights (structure/signaling/pharmacology) Electrical versus Chemical Synapses 2 CamilloJohn Eccles Golgi SantiagoBernard Ramon Katz y Cajal NobelprizeNobelprize 1963 1906 Nobelprize 19701906 “Electrical Synapses” “Chemical Synapses” Electrical Synapses 4 bidirectional Schmidt/Unsicker Fig 2-1 no information processing at the synapse Chemical Synapses: Possibility for reversal of signal 11 Schmidt/Unsicker Fig 2-2 directional information processing at synapse: excitation can be changed in inhibition Chemical Synapses: Inhibitory and excitatory postsynaptic ion channels metabotropic ++ x Ca K+ ionotropic + ++ Na Ca metabotropic - Cl presynaptic postsynaptic 17 Kandel Fig 10.1 Overview History Ionotropic receptors: - Structure and synaptic functions Metabotropic receptors: - Structure and synaptic functions - New insights (structure/signaling/pharmacology) A fundamental principle: Excitatory and inhibitory synapses excitatory inhibitory Purves 3rd Fig. 1.7 Frequency of actionpotentials in neurons of a reflex arc 19 Purves 3rd Fig 1.8 Permeabilites of ions at excitatory and inhibitory synapses (1) glutamate, acetylcholine, ++ serotonin, ATP Depolarisation: Ca Excitability + Na ++ x Ca + Na - Cl - Cl Hyperpolarisation: Inhibition GABA, glycine Permeabilites of ions at excitatory and inhibitory synapses (2) Excitatory: postsynaptic depolarisation Na+, Ca2+ Inhibitory: postsynaptic hyperpolarisation (mostly) Cl-, K+ Purves Tab 2.1 EquiPot -91mV +60mV -82mV +125mV Cl--permeable ion channels are inhibitory even if they lead to depolarization 6 Hyperpolarisation Depolarisation Cl-influx Cl-efflux Purves 3rd Fig 5.19 IPSPs und EPSPs act simultaneously on individual neurons ∑ Hemmung ∑ Erregung Aktionspotentiale ↑ ∑ Erregung ∑ Hemmung Aktionspotentiale ↓ Normal balance between excitation and inhibition Excitation Inhibition n Ex Inhibitio citation n Inh Excitatio ibition EPSPs actionpotential IPSPs no actionpotential Learning/Memory Sleep Abnormal balance between excitation and inhibition Excitation Inhibition Excitation Inhibition anxiety, depression, insomnia, E epilepsy, x c i tat spasticity io n cognitive problems, I n loss of muscle tone, h coma, respiratory arrest ib it io n Excitatory and inhibitory neurotransmitter receptors Purves Fig 7.11 localisation (pre-, post-, extrasynaptic) affinity for the neurotransmitter kinetics ion selectivity (Ca2+) Example NMDA receptors: Overlapping mRNA distribution of 9 receptor subunits NR1 NR2A NR2B NR2C Klinke/Pape Fig 5.12 Cells express distinct subunits receptors with distinct properties Structure of ionotropic neurotransmitter receptors Kandel Fig 11.14 Molecular basis for the ion selectivity of ionotropic acetylcholine receptors Kandel Fig 11.15 A receptors: Site of action of the benzodiazepines Ionotropic GABA L-Gl utamate GABA IPSPs ↑ sleep, anti-epileptic Ionotropic glutamate receptors AMPAKainate NMDA “no” Ca2+ influx Ca2+ influx Ca2+ influx Mg2+ block Auxiliary AMPA receptor subunits influence surface trafficking, pharmacology and kinetics of the receptor response TARPs: transmembrane AMPA receptor regulatory proteins Nature 2000 Science 2010 Nature 2009 TARPs influence pharmacology and kinetics of the AMPA receptor Kato et al., TINS, in press NMDA receptors: Voltage-sensitive Mg2+ block Auswärtsstrom Einwärtsstrom Purves 3rd Fig 6.7 Kinetics of AMPA and NMDA receptors: +50 mV EPSPKainate/AMPA > EPSPNMDA +50 mV +50 mV Purves 3rd Fig 6.7 NMDA receptors do not contribute much to EPSCs at hyperpolarized membrane potentials Kandel Fig 12.7 NMDA receptors act as coincidence detectors during synaptic plasticity processes 2+ Ca + NMDA-R Mg 2 2+ Glutamate Ca -dependent processes AMPA-R + Na+ presynaptic activity: glutamate release postsynaptic activity: depolarisation Longterm potentiation (LTP) after tetanic stimulation LTP is specific for tetanically stimulated synapse 1 After tetanus (1h) to pathway 1 (1h) Before tetanus to pathway 1 Purves 3rd Fig 24.6 ExcitotoxicityNeurodegenerative Prozesse: Exzitotoxizität 1957 junge Mäuse mit Glutamat-Diät: neuronaler Zelltod Retina 1967 neuronaler Zelltod Gehirn Olney: “Glutamat bewirkt neuronalen Zelltod durch langandauernde exzitatorische synaptische Transmission” NMDA Antagonisten blockieren neuronalen Zelltod Kainat induziert neuronalen Zelltod (epileptischen Anfälle) 2+ übermässige [Ca ]i induziert Apoptose (programmierter Zelltod, Proteasen werden aktiviert) Exzitotoxische Prozesse finden statt bei: Ischämie: O2, Glucose 2+ ATP (Glutamat uptake, Em, NMDAR, [Ca ]i, Apoptose) + Tote Neurone entlassen: [K ]e, [Glu]e Hypoglykämie (Diabetes): Glucose Epilepsie (status epilepticus) “Chinese Food Syndrome”, MSG (Mono Sodium Glutamate), “Aromat” Domoat/Kainat Vergiftungen (verdorbene Muscheln) Kainate und AMPA receptors are distinct AMPA kainate Nature 392, 1998 GluR6 is activated by kainate und domoate, but not by AMPA GluR6 subunit makes kainate receptors (Ca2+) Ca2+ Ca2+ permeable for Ca2+ Can GluR6 directly mediate excitotoxicty? GluR6 is predominantly expressed in the CA1 and CA3 regions, which are most susceptible to seizure-induced brain damage GluR6 mediates kainate-mediated excitotoxicity Nature 392, 1998 GluR6 antagonists as anti-epileptic drugs in preclinical trials Overview History Ionotropic receptors: - Structure and synaptic functions - Pathology Metabotropic receptors: - Structure and synaptic functions - New insights (structure/signaling/pharmacology) Classical neurotransmitters activate ionotropic and metabotropic „G-protein coupled receptors“ Metabotropic Purves 3rd + Neuropeptides Fig 6.5 Ionotropic Classification and diversity of GPCRs: Neurotransmitter receptors belong to different gene families -6 families - 7TM domains - no sequence homology between families (evolutionary convergence) - binding sites differ GPCRs activate G-proteins Crystal structure of the human 2-adrenergic receptor bound to the partial inverse agonist carazolol rhodopsin 2000 / 2-adrenergic 2007 Illustration of the central core of rhodopsin in its inactive and active conformation viewed from the cytoplasm Change in TMIII/TMVI domain conformation unmasks G-protein binding site (C-term G) and activates the G-protein Inactive Active Crystal structure of a heterotrimeric G-protein bound to a GPCR Classical signaling pathways of GPCRs: How can they influence to synaptic transmission? G effector systems: Regulation of K+ and Ca2+ channels (1) Heteroreceptors GABA . B . Auto- . Spillover receptors . GABA . G effector systems: Regulation of K+- and Ca2+-channels (2) Activation of Kir3-type K+-channels 1 m baclofen Inhibition of PQ-type Ca2+-channels G effector systems: Phosphorylation of ion channels Purves Fig 8.6 G effector systems: Incorporation of additional ion channels at synapses longterm effects structural plasticity / synaptic plasticity - synapse ↑ - receptors ↑ Purves 3rd Fig 7.11 Overview History Ionotropic receptors: - Structure and synaptic functions - Pathology Metabotropic receptors: - Structure and synaptic functions - New insights (structure/signaling/pharmacology) Cloned GABAB receptor subunits bind GABA but do not activate effector systems Western blot Cortex Mr (K) 1a 1b 130 100 GABAB1 Gene Met 1a Met 1b 2a 3a 4a 5a1b 6 2 sushi domains Agonist afffinity differs between recombinant GABAB1a and GABAB1b proteins and native GABAB receptors + 2+ No efficient functional coupling of GABAB1a and GABAB1b to effector K / Ca channels and adenylate cyclase GABAB1a and GABAB1b are retained in the endoplasmatic reticulum myc-GABAA3 myc-1a 120 non- 100 perm 80 60 40 20 I] anti-myc surface binding (%) 1 3 125 [ A perm A Cmyc-1a Nmyc-1a myc-GABA myc-GABA Couve et al., J. Biol. Chem., 1998 GABAB receptors only function as heterodimeric receptors Nature 396, 1998 Heteromerization between GABAB(1) and GABAB(2) subunits is a prerequisite for receptor function in heterologous cells 1a+1b GABAB(1,2) receptors coupled to Kir3-type K+ channels in Xenopus oocytes 2 1a 1b 2 1a 1b + + 2 2 surface expression coupling to P/Q-, N-type Ca2+ channels negative coupling to adenylate cyclase Increasing number of reports demonstrating the existence of heteromeric GPCRs - 1998: 1st heteromeric GPCR - 2005: 35 heteromeric GPCRs Functional consequences of GPCR heterodimerization change in pharmacology (+ opioid, SSTR5+D2, M2+M3) change in G-protein coupling selectivity (Go/i > Gs + opioid) stabilization of receptor at cell surface (GABAB(1,2), + opioid) increased agonist affinity (GABAB(1,2), SSTR5+D2) Heteromeric GABAB(1,2) receptors display increased affinity for agonists but still do not match native pharmacology Complete loss of GABAB responses in GABAB1 and GABAB2 knockout mice: Core receptor subunits Anti-GABAB1 Anti-GABAB2 WT -/- GABAB1 GABA -/- B2 Schuler et al., Neuron, 2001 Gassmann et al., J. Neurosci., 2004 Fritschy et al., J. Comp. Neurol., 2004 No pharmacological or functional differences between GABAB(1a, 2) and GABAB(1b,2) receptor subtypes in heterologous systems Coupling to Kir3-type K+-channels in Xenopus oocytes GABAB(1a,2) GABAB(1b,2) … but native GABAB responses differ in their pharmacological and kinetic properties Cruz et al., Nature Neurosci., 2004 Possible explanations: - effector channel subunit composition - phosphorylation of the receptor
Load more

Recommended publications
  • The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’S Disease
    life Review The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease Gianfranco Natale 1,2,* , Larisa Ryskalin 1 , Gabriele Morucci 1 , Gloria Lazzeri 1, Alessandro Frati 3,4 and Francesco Fornai 1,4 1 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; [email protected] (L.R.); [email protected] (G.M.); [email protected] (G.L.); [email protected] (F.F.) 2 Museum of Human Anatomy “Filippo Civinini”, University of Pisa, 56126 Pisa, Italy 3 Neurosurgery Division, Human Neurosciences Department, Sapienza University of Rome, 00135 Rome, Italy; [email protected] 4 Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, 86077 Pozzilli, Italy * Correspondence: [email protected] Abstract: The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to Citation: Natale, G.; Ryskalin, L.; identifying various neuronal cytotypes belonging to ENS in baseline conditions.
    [Show full text]
  • Oxytocin Effects in Mothers and Infants During Breastfeeding
    © 2013 SNL All rights reserved REVIEW Oxytocin effects in mothers and infants during breastfeeding Oxytocin integrates the function of several body systems and exerts many effects in mothers and infants during breastfeeding. This article explains the pathways of oxytocin release and reviews how oxytocin can affect behaviour due to its parallel release into the blood circulation and the brain. Oxytocin levels are higher in the infant than in the mother and these levels are affected by mode of birth. The importance of skin-to-skin contact and its association with breastfeeding and mother-infant bonding is discussed. Kerstin Uvnäs Moberg Oxytocin – a system activator increased function of inhibitory alpha-2 3 MD, PhD xytocin, a small peptide of just nine adrenoceptors . Professor of Physiology amino acids, is normally associated The regulation of the release of oxytocin Swedish University of Agriculture O with labour and the milk ejection reflex. is complex and can be affected by different [email protected] However, oxytocin is not only a hormone types of sensory inputs, by hormones such Danielle K. Prime but also a neurotransmitter and a as oestrogen and even by the oxytocin 1,2 molecule itself. This article will focus on PhD paracrine substance in the brain . During Breastfeeding Research Associate breastfeeding it is released into the brain of four major sensory input nervous Medela AG, Baar, Switzerland both mother and infant where it induces a pathways (FIGURES 2 and 3) activated by: great variety of functional responses. 1. Sucking of the mother’s nipple, in which Through three different release pathways the sensory nerves originate in the (FIGURE 1), oxytocin functions rather like a breast.
    [Show full text]
  • Neurotransmitter Actions
    Central University of South Bihar Panchanpur, Gaya, India E-Learning Resources Department of Biotechnology NB: These materials are taken/borrowed/modified/compiled from various resources like research articles and freely available internet websites, and are meant to be used solely for the teaching purpose in a public university, and for serving the needs of specified educational programmes. Dr. Jawaid Ahsan Assistant Professor Department of Biotechnology Central University of South Bihar (CUSB) Course Code: MSBTN2003E04 Course Name: Neuroscience Neurotransmitter Actions • Excitatory Action: – A neurotransmitter that puts a neuron closer to an action potential (facilitation) or causes an action potential • Inhibitory Action: – A neurotransmitter that moves a neuron further away from an action potential • Response of neuron: – Responds according to the sum of all the neurotransmitters received at one time Neurotransmitters • Acetylcholine • Monoamines – modified amino acids • Amino acids • Neuropeptides- short chains of amino acids • Depression: – Caused by the imbalances of neurotransmitters • Many drugs imitate neurotransmitters – Ex: Prozac, zoloft, alcohol, drugs, tobacco Release of Neurotransmitters • When an action potential reaches the end of an axon, Ca+ channels in the neuron open • Causes Ca+ to rush in – Cause the synaptic vesicles to fuse with the cell membrane – Release the neurotransmitters into the synaptic cleft • After binding, neurotransmitters will either: – Be destroyed in the synaptic cleft OR – Taken back in to surrounding neurons (reuptake) Excitable cells: Definition: Refers to the ability of some cells to be electrically excited resulting in the generation of action potentials. Neurons, muscle cells (skeletal, cardiac, and smooth), and some endocrine cells (e.g., insulin- releasing pancreatic β cells) are excitable cells.
    [Show full text]
  • Oxytocinergic-System-A-Proposal.Pdf
    Opinion Article iMedPub Journals ACTA PSYCHOPATHOLOGICA 2018 www.imedpub.com ISSN 2469-6676 Vol.4 No.3:14 DOI: 10.4172/2469-6676.100170 Oxytocinergic System: A Proposal João Paulo Correia Lima* and Avelino Luiz Rodrigues Received: April 17, 2018; Accepted: May 07, 2018; Published: May 18, 2018 Department of Clinical Psychology and Nucleus of Neuroscience and Behavior, Institute of Psychology, University of Sao Introduction Paulo, Brazil Since 1910, when Ott and Scott [1] published their discovers about the oxytocin participation in milk ejection, the comprehension *Corresponding author: about function and role of oxytocin in several physiological João Paulo Correia Lima functions didn’t stop enlarging and growing. In birth, through his action over uterus contractions, in uterus contractions in [email protected] women’s orgasm and men’s erection [2,3], for instance. However, this approach always considers its peripheral effects. After this, Psychologist for Neuroscience and Behavior, some oxytocin effects had been reported to have actions over Institute of Psychology, University of Sao behavioural traits, like we can see in publishings of Pedersen and Paulo, Brazil. Prange [4] and Winslow and co-workers [5], reporting the oxytocin actions over, respectively, maternal behaviour and pair bonding. Tel: +55-11-32852420; +55-11-983439754 Since then, the increasing data about the oxytocin’s function in behaviour and its central action can’t be ignored. In this short proposal, we’ll consider the opportunity or utility of thinking Citation about oxytocin as a system, instead of a single neurotransmitter. : Lima JPC, Rodrigues AL (2018) Oxytocinergic System: A Proposal. Acta Neurotransmitter or Hormone: Central Psychopathol Vol.4 No.3:14 and Peripheral Actions of Oxytocin Once a molecule could have his function defined through the way death, passive avoidance).
    [Show full text]
  • Neuroscience: the Science of the Brain
    NEUROSCIENCE SCIENCE OF THE BRAIN AN INTRODUCTION FOR YOUNG STUDENTS British Neuroscience Association European Dana Alliance for the Brain Neuroscience: the Science of the Brain 1 The Nervous System P2 2 Neurons and the Action Potential P4 3 Chemical Messengers P7 4 Drugs and the Brain P9 5 Touch and Pain P11 6 Vision P14 Inside our heads, weighing about 1.5 kg, is an astonishing living organ consisting of 7 Movement P19 billions of tiny cells. It enables us to sense the world around us, to think and to talk. The human brain is the most complex organ of the body, and arguably the most 8 The Developing P22 complex thing on earth. This booklet is an introduction for young students. Nervous System In this booklet, we describe what we know about how the brain works and how much 9 Dyslexia P25 there still is to learn. Its study involves scientists and medical doctors from many disciplines, ranging from molecular biology through to experimental psychology, as well as the disciplines of anatomy, physiology and pharmacology. Their shared 10 Plasticity P27 interest has led to a new discipline called neuroscience - the science of the brain. 11 Learning and Memory P30 The brain described in our booklet can do a lot but not everything. It has nerve cells - its building blocks - and these are connected together in networks. These 12 Stress P35 networks are in a constant state of electrical and chemical activity. The brain we describe can see and feel. It can sense pain and its chemical tricks help control the uncomfortable effects of pain.
    [Show full text]
  • Mechanism for Neurotransmitter-Receptor Matching
    Mechanism for neurotransmitter-receptor matching Dena R. Hammond-Weinbergera,1,2, Yunxin Wanga, Alex Glavis-Blooma, and Nicholas C. Spitzera,b,1 aNeurobiology Section, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093-0357; and bCenter for Neural Circuits and Behavior, Kavli Institute for Brain and Mind, University of California San Diego, La Jolla, CA 92161 Contributed by Nicholas C. Spitzer, January 6, 2020 (sent for review September 25, 2019; reviewed by Laura N. Borodinsky and Joshua R. Sanes) Synaptic communication requires the expression of functional neurons lead to the appearance of functional neuromuscular postsynaptic receptors that match the presynaptically released junctions expressing GluR1 and GluR2 (alias GluA1 and GluA2) neurotransmitter. The ability of neurons to switch the transmitter subunits, which are blocked by the AMPA receptor antagonist they release is increasingly well documented, and these switches GYKI 52466 (16, 17). In the central nervous system, the natural require changes in the postsynaptic receptor population. Al- developmental transmitter switch from GABA to glycine in the though the activity-dependent molecular mechanism of neuro- auditory nervous system is accompanied by alterations in the transmitter switching is increasingly well understood, the basis properties of postsynaptic receptors (18, 19). Changes in illumi- of specification of postsynaptic neurotransmitter receptors match- nation during development or in photoperiod in the adult lead to ing the newly expressed transmitter is unknown. Using a func- changes in the numbers of neurons expressing dopamine in the tional assay, we show that sustained application of glutamate to embryonic vertebrate skeletal muscle cells cultured before hypothalamus that are accompanied by corresponding up- or innervation is necessary and sufficient to up-regulate ionotropic down-regulation of dopamine receptor expression in postsynaptic glutamate receptors from a pool of different receptors expressed neurons (5, 7).
    [Show full text]
  • Neurotransmitter Notes
    Synapses and Neurotransmitters Notes Chemical Transmitters called “Neurotransmitters” carry a signal across Synapses (& at Neuromuscular Junctions) A point of contact between two neurons is called a synapse At the synapse there is a break in electrical transmission (the action potential cannot cross). Instead chemicals called “neurotransmitters” are released that carry the signal to the next nerve. There is a delay at synapses, because chemical transmission between neurons is slower than electrical transmission (action potential) within a neuron. A neuromuscular junction (NMJ) is a contact between a neuron and a muscle: it is like a synapse in that the action potential stops and the signal is carried by a chemical neurotransmitter released by the neuron. Neurotransmitters Are Made and Stored in the Pre-synaptic Terminal The end of the neuron enlarges into an axon terminal Neurotransmitters are produced in the cell body of a neuron and then transported to the ends of the axon terminals in small membrane-enclosed sacs called “synaptic vesicles”. At the axon terminus, neurotransmitters are stored in these tiny synaptic vesicles so that they can be released when an action potential reaches the axon terminus At a synapse, axon termini of the pre-synaptic neuron contact the dendrites of the post-synaptic neuron. Because the neurotransmitter is only located in the axon termini on one side of a synapse, the impulse can go in only one direction. Calcium is Required for Neurotransmitter Release Neurotransmitter release requires Ca2+ ions Normally, the concentration of Ca2+ in the pre-synaptic neuron l is kept very low (by the action of a Ca pump).
    [Show full text]
  • 5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice
    Neuropsychopharmacology (2017) 42, 2163–2177 © 2017 American College of Neuropsychopharmacology. All rights reserved 0893-133X/17 www.neuropsychopharmacology.org 5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice 1 1,2 3,7 4 1 Vladimir M Pogorelov , Ramona M Rodriguiz , Jianjun Cheng , Mei Huang , Claire M Schmerberg , 4 5 3 ,1,2,6 Herbert Y Meltzer , Bryan L Roth , Alan P Kozikowski and William C Wetsel* 1 2 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Mouse Behavioral and Neuroendocrine 3 Analysis Core Facility, Duke University Medical Center, Durham, NC, USA; Drug Discovery Program, Department of Medicinal Chemistry and 4 Pharmacognosy, College of Pharmacy, University of Illinois, Chicago, IL, USA; Department of Psychiatry and Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina Chapel Hill Medical School, Chapel Hill, NC, 6 USA; Departments of Cell Biology and Neurobiology, Duke University Medical Center, Durham, NC, USA All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests that additional drug targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT receptors may be a promising target for 2C schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss-promoting capabilities.
    [Show full text]
  • Recent Advances in the Detection of Neurotransmitters
    chemosensors Review Recent Advances in the Detection of Neurotransmitters Bo Si 1 and Edward Song 1,2,* ID 1 Department of Electrical and Computer Engineering, University of New Hampshire, Durham, NH 03824, USA; [email protected] 2 Center for Advanced Materials and Manufacturing Innovation, University of New Hampshire, Durham, NH 03824, USA * Correspondence: [email protected]; Tel.: +1-603-862-5498 Received: 3 December 2017; Accepted: 2 January 2018; Published: 4 January 2018 Abstract: Neurotransmitters are chemicals that act as messengers in the synaptic transmission process. They are essential for human health and any imbalance in their activities can cause serious mental disorders such as Parkinson’s disease, schizophrenia, and Alzheimer’s disease. Hence, monitoring the concentrations of various neurotransmitters is of great importance in studying and diagnosing such mental illnesses. Recently, many researchers have explored the use of unique materials for developing biosensors for both in vivo and ex vivo neurotransmitter detection. A combination of nanomaterials, polymers, and biomolecules were incorporated to implement such sensor devices. For in vivo detection, electrochemical sensing has been commonly applied, with fast-scan cyclic voltammetry being the most promising technique to date, due to the advantages such as easy miniaturization, simple device architecture, and high sensitivity. However, the main challenges for in vivo electrochemical neurotransmitter sensors are limited target selectivity, large background signal and noise, and device fouling and degradation over time. Therefore, achieving simultaneous detection of multiple neurotransmitters in real time with long-term stability remains the focus of research. The purpose of this review paper is to summarize the recently developed sensing techniques with the focus on neurotransmitters as the target analyte, and to discuss the outlook of simultaneous detection of multiple neurotransmitter species.
    [Show full text]
  • Psychopharmacology Handout
    5/17/2017 Psychopharmacology Robert M. Millay RN, MSN Ed Psychiatric Technician Programs Napa Valley College Important Neurotransmitters • Acetylcholine • Dopamine • GABA (gamma-aminobutyric acid) • Glutamate • Norepinephrine • Serotonin Acetylcholine Receptors: • Nicotine • Muscarine – Memory – Anticholinergic side effects 1 5/17/2017 Dopamine Receptors: • Nigrostriatal: Movement • Mesolimbic: Pleasure, delusions/hallucinations • Mesocortical: Mediates positive and negative symptoms, cognitive side effects • Tuberoinfundibular: Prolactin release Glutamate –v‐GABA • Excitatory neurotransmitter Serotonin & Norepinephrine • Inhibitory catecholamine • Mediates: – Cognitive effects – Emotions, including panic – Memory and anxiety – Violence and aggression – Sexual function – Sleep‐wake cycles 2 5/17/2017 Drug‐Related Variables • Mode/mechanism of action • Dosage form • Bioavailability • Onset, peak, duration of action • Serum, half‐life • Elimination method • Side effects/toxicities • Cost Client‐Related Variables • Diagnosis • Other disease states • Age • Weight • Anticholinergic susceptibility • History of side effects • Previous response • Compliance • Financial/insurance • Support system Antipsychotics Typical • Block D2 receptors • Differ in potency and side effects Atypical • Differ in mode of action, side effect, potency • Fewer… • Greater efficacy with negative symptoms… • Lower potential to increase… 3 5/17/2017 Symptom Dimensions of Psychosis Positive symptoms related to overactive dopamine neurons in mesolimbic pathway • Examples:
    [Show full text]
  • Building a Second Brain in the Bowel
    Building a second brain in the bowel Marina Avetisyan, … , Ellen Merrick Schill, Robert O. Heuckeroth J Clin Invest. 2015;125(3):899-907. https://doi.org/10.1172/JCI76307. Review Series The enteric nervous system (ENS) is sometimes called the “second brain” because of the diversity of neuronal cell types and complex, integrated circuits that permit the ENS to autonomously regulate many processes in the bowel. Mechanisms supporting ENS development are intricate, with numerous proteins, small molecules, and nutrients that affect ENS morphogenesis and mature function. Damage to the ENS or developmental defects cause vomiting, abdominal pain, constipation, growth failure, and early death. Here, we review molecular mechanisms and cellular processes that govern ENS development, identify areas in which more investigation is needed, and discuss the clinical implications of new basic research. Find the latest version: https://jci.me/76307/pdf The Journal of Clinical Investigation REVIEW SERIES: ENTERIC NERVOUS SYSTEM Series Editor: Rodger Liddle Building a second brain in the bowel Marina Avetisyan,1 Ellen Merrick Schill,1 and Robert O. Heuckeroth2 1Washington University School of Medicine, St. Louis, Missouri, USA. 2Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. The enteric nervous system (ENS) is sometimes called the “second brain” because of the diversity of neuronal cell types and complex, integrated circuits that permit the ENS to autonomously regulate many processes in the bowel. Mechanisms supporting ENS development are intricate, with numerous proteins, small molecules, and nutrients that affect ENS morphogenesis and mature function. Damage to the ENS or developmental defects cause vomiting, abdominal pain, constipation, growth failure, and early death.
    [Show full text]
  • Neurotransmission Fact Sheet
    Neurotransmission Fact Sheet The brain and nervous system are made of billions of nerve cells, called neurons. Neurons have three main parts: cell body, dendrites, and axon. The axon is covered by the myelin sheath. Cell Body is in charge of the neuron’s Dendrites receive messages activities. from other neurons. Myelin Sheath covers the axon to protect it and help messages travel faster and easier. Axon sends messages from the cell body to the dendrites of other neurons. The transfer of information between neurons is called neurotransmission. This is how neurotransmission works: 1. A message travels from the dendrites through the cell body and to the end of the axon. 2. The message causes the chemicals, called neurotransmitters, to be released from the end of the axon into the synapse. The neurotransmitters carry the message with them into the synapse. The synapse is the space between the axon of one neuron and the dendrites of another neuron. 3. The neurotransmitters then travel across the synapse to special places on the dendrites of the next neuron, called receptors. The neurotransmitters fit into the receptors like keys in locks. 4. Once the neurotransmitter has attached to the receptors of the second neuron, the message is passed on. 5. The neurotransmitters are released from the receptors and are either broken down or go back into the axon of the first neuron. Teacher copy: Module 1 Neurotransmission Fact Sheet The brain and nervous system are made of billions of nerve cells, called neurons. Neurons have three main parts: cell body, dendrites, and axon.
    [Show full text]