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Psych 181: Dr. Anagnostaras
Lecture 5
Synaptic Transmission
Introduction to synaptic transmission
Synapses(Gk., to clasp or join)
Site of action of mostpsychoactive drugs
6.5
2
Synapses
Know basic terminology: Soma Axon Dendrite Synaptic vesicles Synaptic cleft Postsynaptic Presynaptic Glia
6.2
Synapses
Dendrites &spines
3.10
Synapses
Types of cell-cell junctionsTight junctions
membranes fusedGap junctions
close juxtaposition (2-4 nm) electrical synapse
Chemical synapses synaptic cleft (20-30 nm) polarized
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Multiple types of synapses
Vesicle varieties
6.46.3
+
-
Multiple types of synapses
Multiple patterns of connectivityAxodendriticDendrodendriticAxoaxonicAxosomaticetc.
6.1
Steps in synaptic transmission
Synthesis Transport Storage Release Inactivation
4
Release
Excitation-secretion coupling Depolarization Open voltage-gated Ca++ channels Ca++ influx Bind to Ca++ -calmodulin protein kinase Phosphorylation of synapsin I Movement of vesicles to release site Exocytosis Diffusion
Exocytosis
6.17
Inactivation
Reuptake transporters
Enzymaticdegradation metabolism excretion cycling
8.13
5
Sample questionIn which of the following are the events listed in the correct temporalorder (i.e., the temporal order associated with excitation-secretioncoupling)?
(a) Depolarization > calcium influx > phosphorylation of synapsin >activation of calcium-calmodulin protein kinase > exocytosis(b) Depolarization > calcium influx > activation of calcium-calmodulinprotein kinase > phosphorylation of synapsin > reuptake > exocytosis(c) Exocytosis > phosphorylation of synapsin > calcium influx >activation of calcium-calmodulin protein kinase > depolarization >calcium influx(d) Enzymatic degradation > exocytosis > activation of calcium-calmodulin protein kinase > phosphorylation of synapsin > calcium influx> depolarization(e) Depolarization > calcium influx > activation of calcium-calmodulinprotein kinase > phosphorylation of synapsin > exocytosis > enzymaticdegradation
Neurotransmitters
Two major types:
“Classical” small water soluble molecules with amine formed from dietary precursors
Neuropeptides protein synthesis
Neurotransmitters
Phenylethylamines DA, NE, E, tyramine, etc.
Indoleamines 5-HT, tryptamine, melatonin, etc.
CholinergicsAmino acidsNeuropeptides
Enkephalins, substance P, neurotensin, etc.
Nonpeptide hormones
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Receptors
6.5
Receptors
Classification
By Location Postsynaptic
DA
GABA
ACH
Receptors
Classification
By Location Postsynaptic Autoreceptors
DA
GABA
ACH
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Autoreceptors
Presynaptic Somatodendritic Terminal
Release-modulating Synthesis-modulating Impulse-modulating
DA
GABA
ACH
Receptors
Classification:By Transduction Mechanism
Drug, transmitteror hormone
Receptor
EffectorMembrane
Transduction
Outside cell
Inside cell
Receptor Superfamilies
1. Ligand-gated channels binding site coupled to ion channel transmitter (or drug) gates the channel ionotropic receptors
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Receptor Superfamilies
1. Ligand-gated channels
2. G protein-coupled receptor coupled to G protein G protein activates effector metabotropic receptors
Ligand-gated channels
Ligand opens channel Ions flow down conc.
gradient Rapid Rapidly
reversible
5.9
Ligand-gated channels
Examples:Nicotinic acetylcholine receptor
coupled to sodium channel drugs: nicotine, curare
GABAA receptor coupled to chloride
channel drugs: sedative-
hypnotics
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G protein-coupled receptors
G protein-coupled receptors
Large family all with7 membrane-spanning regions
Receptor coupledto G protein, and Gprotein stimulateseffector
Slower thanion-coupled
6.22
G protein-coupled receptors
Two classes:
G protein directly coupled to ion channel effector is ion channel
G protein coupled to 2nd messenger system effector is enzyme that promotes formation
of intracellular “second messenger”
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G protein-coupled receptors
Examples:
Cholinergicmuscarinic
GABA B 5-HT Opioid Dopamine Norepin-
ephrine
Second messengers
Are many: Calcium cGMP Phosphoinositides
(IP3, diacylglycerol) cAMP
cAMP(cyclic adenosine 3,5-monophosphate)
cAMP
6.22
1
2 3
4
5
67
8 9
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Protein phosphorylation
Changes structure/function of proteinConsequence depends on function of protein
ion channel proteins enzymes cytoskeletal proteins vesicular proteins receptors gene regulatory proteins
Second messengers and protein kinases have many targets
from P. Greengard, Science, 2001
from P. Greengard, Science, 2001
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Gene regulation
Second messengers can alter gene regulation:
Activate transcription factors Regulate transcription
enhance or supress If enhance - new gene products
Gene regulation
Two phases of gene activation:Initial phase
induction of immediate-early genes (IEGs)(e.g., cfos, c-jun, zif-268, etc.)
protein products initiate 2nd phaseSecond phase
induction of “late-onset genes” products that alter cellular function
Gene regulation by cAMP
R= regulatory subunitC= catalytic subunit
Transcription factor: CREB (cAMP responseelement binding protein)
CREB stimulates genetranscription (eg., IEGs)
6.34
13
Convergence on CREB
6.35
Multiple signallingpathways can altergene transcriptionvia sametranscriptionfactor
2nd messengerskinases
Summary
6.37
Drugs ofabuse arevery effectivein inducingIRGs
6.37
Home
Saline
Novel
Amphetaminec-fos mRNA Expression
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Sites of drug action
6.2
Sample question
Which of the following classes of drug action wouldhave in common the effect of increasing synaptictransmission?
(a) facilitation of release; block reuptake; inhibition of synthesis(b) blockade of the release modulating autoreceptor; facilitation
of release; receptor agonist(c) receptor agonist; receptor antagonist; synthesis inhibition(d) reuptake blocker; facilitation of release; receptor antagonist(e) blocks metabolism; block reuptake; inhibits synthesis