Synaptic Transmission Synaptic Events Action Potential reaches axon

Synaptic Transmission

Synaptic Events Action Potential reaches axon terminal n Chemical substance released Neurotransmitter (NT) n Diffuses across synapse n Binds to receptor protein EPSP or IPSP ~ n

Synaptic Transmission Model Precursor transport n NT synthesis n Storage n Release n Activation n Termination ~ n

Presynaptic Axon Terminal Button Postsynaptic Membrane Dendritic Spine

1. Precursor Transport

2. Synthesis _ _ _ enzymes/cofactors NT

3. Storage in vesicles

NT Terminal Button Dendritic Spine Synapse Vesicles

4. Release Terminal Button Dendritic Spine Synapse Receptors

Terminal Button AP Dendritic Spine Synapse

Exocytosis Ca++

5. Activation

6. Termination

6. Termination by. . . Diffusion

6. Termination by. . . Enzymatic degradation

6. Termination by. . . Reuptake

6. Termination by. . . Autoreceptors A

Autoreceptors On presynaptic terminal n Binds NT same as postsynaptic receptors different receptor subtype n Decreases NT release & synthesis n Metabotropic receptors l alters protein synthesis ~ n

Receptor Activation Ionotropic channel l directly controls channel l fast n Metabotropic channel l second messenger systems l receptor indirectly controls channel ~ n

Ionotropic Channels Channel NT neurotransmitter

Ionotropic Channels NT Pore

Ionotropic Channels NT

Ionotropic Channels NT

Metabotropic Channels Receptor separate from channel n 2 d messenger system l G proteins l c. AMP l other types n Effects l Control channel l Alter properties of receptors l regulation of gene expression ~ n

G protein: direct control NT is 1 st messenger n G protein binds to channel l opens or closes l relatively fast ~ n

G protein: direct control R G GDP

G protein: direct control R G GTP Pore

G protein: Protein Phosphorylation Open or close channels at resting Vm n NT = 1 st messenger n Membrane-associated components l Receptor l Transducer l Primary effector n Intracellular l 2 d messenger l Secondary effector ~ n

G protein: Protein Phosphorylation external signal: nt norepinephrine Receptor b adrenergic -R transducer primary effector GS adenylyl cyclase 2 d messenger c. AMP secondary effector protein kinase

G protein: Protein Phosphorylation A C R G GDP PK

G protein: Protein Phosphorylation A C R G GTP ATP c. AMP PK

G protein: Protein Phosphorylation A C R G GTP ATP P c. AMP PK Pore