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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

3

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

7

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

9

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

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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