Long-Term Potentiation and Depression in Synapses

Study Notes

Long-Term Potentiation (LTP) and Phosphorylation

Repeated synapse use increases transmitter release (LTP), a basis for learning and memory.
Multiple stimuli can decrease release (LTD), also part of learning and memory.
Protein phosphorylation is crucial for both LTP and LTD, modifying synaptic strength.

Protein Phosphorylation and Vesicle Release

Vesicle release proteins are phosphorylated by PKA, a cAMP-stimulated enzyme.
Adenylyl cyclase, stimulated by Gs proteins and inhibited by Gi proteins, produces cAMP.
Active PKA quickens SNARE complex formation, increasing synaptic vesicle availability and strengthening responses.
PKA increases the pool of synaptic vesicles at the active zone.

Long-Term Depression (LTD) and Potassium Channels

LTD involves potassium channel opening, stabilizing membrane potential at a more negative level.
PKA increases potassium permeability via inward rectifier channel activity and reduced action potential bursts, also affecting ATP-sensitive potassium channels.

Phosphorylation and RAS Superfamily

RAS superfamily (Ras, Rab, Rho, Ran, Arf) are activated when GDP is replaced by GTP.
GTP alters RAS conformation for downstream target binding and activation of kinase activity.
RAS proteins have inherent GTPase activity, hydrolyzing GTP to GDP and returning to inactive states.
The duration of GTP-bound RAS is affected by GTPase acceleration, typically by GAPs (GTPase activating proteins).
GEFs (guanine nucleotide exchange factors) remove tightly bound GDP, allowing GTP substitution.
GEFs are indirectly produced from second messengers (e.g., cAMP, calcium) or directly by growth factor receptors.
GDIs (guanosine nucleotide dissociation inhibitors) stabilize inactive Rho-type kinase forms by preventing GEF action.

GTPase Regulation

GTPase activity is sped up by GAPs (GTPase activating proteins).
GEFs (guanine nucleotide exchange factors) remove tightly bound GDP, allowing GTP substitution.
GEFs are indirectly produced from second messengers (e.g., cAMP, calcium) or directly by growth factor receptors.
GDIs (guanosine nucleotide dissociation inhibitors) stabilize inactive Rho-type kinase forms by preventing GEF action.

Small G Proteins and LTP

Small G proteins, like Epac (GEF for Rap), are directly activated by cAMP and increase synaptic current amplitude.
RAB3A, binding to synaptic vesicle membranes, is regulated by GRAB (GEF).

Description

This quiz covers the mechanisms of Long-Term Potentiation (LTP) and Long-Term Depression (LTD) in synaptic function, emphasizing the roles of protein phosphorylation and synaptic vesicle release. Understand how repeated synapse use influences neurotransmitter release and how potassium channels contribute to LTD as part of the learning and memory processes.