Neuronal Transmissio

nBN Fall 2011Julia Sobesky

Outline

• Types of synapses• Electrical• Chemical

• Neurotransmitters• Criteria• Types• Release• Inactivation

• Receptor types• Ionotropic• Metabotropic

• Ligand binding

• Plasticity

Electrical synapse: gap junctions

• ~3nm apart

• Very fast communication

• Direct pore between cells, allows bidirectional flow of ions

• 6 connexins= 1 connexon

• Allows rapid and synchronous firing of interconnected cells

Why would we need anything more?

• Why don’t our brains just use electrical transmission?

Benefits of Chemical signaling

• 60+ different NTs and neuromodulators• Each NT can have up to 15 different

receptors• Co-localization of several NTs in one

synapse• One neuron can have TONS of different

synapses• Simple or complex post-synaptic

responses

The chemical synapse

• ~20-50 nm apart

• NTs released by pre-synaptic cell bind receptors on post-synaptic membrane

• EPSP, IPSP or complex responses

• *** The RECEPTOR determines the response, not the NT ***

Criteria for NTs• Synthesized in pre-

synaptic cell

• Activity dependent release

• Mechanism for deactivation

• Predictable pharmacological activity

Major classes of neurotransmitters

• Small neurotransmitter molecules • Synthesized near axon terminals• Acetylcholine, monoamines, indolamines, amino

acids

• Large neurotransmitter molecules- Neuropeptides• Synthesized in soma • hormones• enkephalin/ endorphin

• Soluble gasses• nitric oxide • carbon monoxide

Small Neurotransmitters

• 1. Amino Acids• Glutamate/ Gamma-aminobutyric acid (GABA)

• MAJOR NTs in the CNS/ All over

• 2. The Monoamines• Catecholamines

• Dopamine- DA- reward/movement• Norepinephrine- NE –sympathetic• Epinephrine-released from adrenals

• Indolamines• Serotonin -5-HT

• 3. Acetylcholine (ACh)

Glutamic AcidDecarboxylase (GAD)

Tyrosine Hydroxylase

Then what?• NTs are synthesized at terminal and

packaged• Or• Neuropeptides are transcribed, translated,

packaged and trafficked down to the terminal

• How does an Action Potential initiate their release?

Exocytosis

SNARE Proteins

Ca++ facilitated

What happens to NTs after release?

• Diffusion through synapse to post-synaptic cell

• NT binding to receptors is TRANSITORY, more NT around to bind, the greater the receptor effects

• …….

2 Main Types of Receptors

Ionotropic• Ligand-gated ion

channels• Directly alters the

membrane potential

Metabotropic• Slower, but can

have greater effects

• 2 types: • G-protein coupled• Tyrosine Kinase

receptors

Ionotropic Receptors• Excitatory (EPSP) or

Inhibitory (IPSP) responses

• K+, Na+, Ca++

• CL-

• Some can be ligand and voltage-gated (NMDA)

Complex effects of metabotropic

receptors• NO PORE, but binding can initiate:

• 2nd messenger system

• Other products could open ion channels

• Modulate enzyme activity

• Regulate ion channels in membrane

• Initiate gene transcription/translation

What happens to NTs after release?

• Diffusion through synapse to post-synaptic cell

• NT binding to receptors is TRANSITORY, more NT around to bind, the greater the receptor effects

• NT must be cleared • removal just as important as release

• Multiple things can happen….

Uptake and degradation

Glial Sponge• Glial cells can act

as buffers for excess NTs

• Can process and release NTs

• Passive diffusion away from the synapse• Why?

NT binding to receptor shape-

specific• Lock and key arrangement

• Endogenous vs. exogenous

• Drugs work because we already have the receptors in place to receive them

• Drug actions are so intense because they cause actions so far above and beyond what endogenous compounds do

• Agonists

• Antagonists

• Full vs. partial

• Competitive vs. non-competitive

• Allosteric

Receptor agonists and antagonists

Organization dictated by experience

• Synapses can grow and retract, continually being altered by use

• Plasticity can occur in a variety of ways:• Create new synapses• Strengthen or weaken

existing synapses• Break old connections

Synaptic connections change over time

Putting it all together:

Neuropharmacology• Tolerance develops

due to cellular and receptor alterations in response to chronic drug use

• The changes also mediate withdrawal symptoms

• Withdrawal= opposite of drug effects

• Depression is most likely not due to a lack of serotonin (i.e. SSRIs)

• …Serotonin receptor is metabotropic

• Severe alcohol withdrawal can kill you: • Seizures• Glutamate

excitotoxicity

Organization dictated by experience

Thanks! Questions?