Please enable JavaScript.
Coggle requires JavaScript to display documents.
Chapter 25: Molecular Mechanisms: learning/memory (LTP in hippocampal…
Chapter 25: Molecular Mechanisms: learning/memory
LTP in hippocampal slices: an ideal memory mechanism
rapid onset, activity dependent, long-lasting increase in synaptic strength
induced by high frequency stimulation
first found in hippocampus (already implicated in memory) also occurs in cortex, amygdala, striatum, other regions
synapse-specific
associative/cooperative (Hebb's rule)
Early and late phase LTP
E-LTP: 1 tetanus, response DECAYS QUICKLY
L-LTP: more stimulation, SUSTAINED response
Properties of LTP in CA1
to induce LTP, input 1 axons are given tetanus (burst of high frequency stimulation)
LTP is INPUT SPECIFIC: input 2 does NOT show LTP
What is required for LTP
synapses be active at the SAME TIME that the postsynaptic CA1 neuron is STRONGLY DEPOLARIZED
To achieve necessary DEPOLARIZATION with tetanus
high frequency stimulation causes TEMPORAL SUMMATION
enough synapses must be active to cause SPATIAL SUMMATION (cooperativity)
NMDA conducts Ca++ only when glutamate binds and postsynaptic is depolarized to remove Mg++
Without NMDA, there's no LTP involved
APV blocks NMDA receptors --> no LTP
AMPA receptors provide depolarization with, through temporal and spatial summation, may OPEN some NMDA receptors
Glutamate receptor trafficking
AMPA receptors are CONTINUALLY being ADDED and REMOVED from the membrane
LTD and LTP disrupt equilibrium and lead to net increase or decrease in AMPA receptors in membrane
LTP requires MORE synaptic capacity for AMPA receptors and more AMPA receptors
LTD requires LESS synaptic capacity and loss of AMPA receptors
Kinases and AMPA trafficking
Short term plasticity: covalent modification of preexisting proteins (PHOSPHORYLATION of channels or receptors)
CamKII is the most important kinase for short-term LTP
anything kinases do, phosphates can UNDO
phosphorylation of preexisting proteins cannot account for long term memory
Memory consolidation: PERSISTENTLY active protein kinases
required for LTP IN CA1: entry of Ca++ into postsynaptic cell AND activation of CamKII
CamKII subunits connected by a hinge: catalytic and regulatory regions
catalytic region (performs phosphorylation reaction)
regulatory region
Hinge of CamKII is "off" when REGULATORY region COVERS CATALYTIC region
Hinge opens (CamKII activated) by Ca++ bound calmodulin (second messenger)
can phosphorylate AMPA receptors
1 more item...
Long term plasticity (and memory) requires activation of gene transcription and SYNTHESIS of new proteins, via PKA and/or CaMKII and CREB
1st step in protein synthesis: generation of mRNA transcript of a gene
CREB binds to specific segments of DNA (CREs) (Regulates expression of neighboring genes)
2 forms of CREB
CREB-2: REPRESSES gene expression when it binds to CRE
CREB-1 ACTIVATES transcription (only when it's phosphorylated by protein kinase A)
What do CREB-driven genes DO?
facilitate formation of new synapses
add new Ca++ channels to SN
increase persistent activation of protein kinase A
Add new AMPA-type receptors to MN
stabilize newly added AMPA receptors
Aplysia californica
Behavior: gill-withdrawal reflex: gill retracts when water is sprayed on siphon
Associative long-term learning in Aplysia: Classical conditioning
weak stimulus to siphon (conditioned stimulus) is paired with shock to the tail (unconditioned stimulus)
learn to ASSOCIATE stimulus with shock and RETRACT gill
Coincidence detection by Aplysia Californica type I
stimulus to the tail activates serotonergic modulatory neurons that influence SYNAPTIC TRANSMISSION at sensory-motor synapse
serotonin stimulates RISE in cAMP and ACTIVATION of PKA
causing INCREASE release of GLUTAMATE when siphon is touched
REPEATED ACTIVATION of serotonergic modulatory neurons cause long-term SENSITIZATION, requiring new gene expression and protein synthesis
What BLOCKS long-term memory in Aplysia
serotonin antagonists
PKA, CaMKII or PKC inhibitors
transcription inhibiotrs
protein synthesis inhibitors
reduction in CREB activity
Classical Conditioning and fear
when a conditioned stimulus (tone) is paired with unconditioned stimulus (shock)
tone is CONDITIONED to produce fear (conditioned response)
this cued fear depends on AMYGDALA
channel rhodopsin can be used as a stand-in for the tone
main advantage of using CHR
being able to reliably fire the same neurons in repeated rounds
induce LTD in those same neurons
conditioned fear disappears along with decrease synaptic strength (bring it back with LTP)