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Synaptic plasticity
ability of a synapse between 2 neurons to change in strength
Hebbian plasticity
Cells that fire together, wire together
(General principle underlying LTP)
Aplysia as a model system for studying plasticity
-Simple nervous system
-Easily charcterized/studied behavioral reflexes can be modified through learning
Habituation
decrease in behavioral response to a stimulus after repeated exposure to that stimulus over-time
Habituation of the gill-reflex
Touching or applying water pressure to the siphon of Aplysia results in activation of
the gill withdrawal response
-After multiple rounds of siphon stimulation, the gill-withdrawl response weakens
Sensitization
Non-associative learning type, where behavioral responses are amplified in reaction to repeated stimulus
Sensitization of gill-withdrawl
After habituation, pairing a noxious/electrical stimulus to the tail while applying
pressure to the siphon reinstates the gill withdrawal reflex and increases the
strength of the response compared to baseline
-This sensitization is long-lasting; would take alot longer for the response to habituate again
Post-synaptic mechanisms
change in number or conductance of post-synaptic receptors, activation or inactivation of ion channels
Pre-synaptic mechanisms
Change in Ca2+ influx to the synaptic terminal which would change the amount of NT release
Seratonin in gillwithdrawl response
Seratonin(5H-T) release from L29 neuron (neuron that recieves electrical stimulus applied to tail) leads to changes in the synaptic terminal of the sensory neuron
What does 5-HT/Seratonin act at?
A GPCR on the sensory neuron, activates second messenger cascades —> depolarization of the sensory cell, more NT released onto MN —> sensitization of the gillwithdrawl response
Long-term sensization
can be elicted by applying multiple shocks (noxious stimuli) to the tail rather than just 1, the senitizing effect is long lasting (weeks)
CREB acts as..
a transcription factor, promoting expression of certain genes
WHat does CREB lead to
further increase in PKA activity, activates C/EBP (another transcription factor) that promotes growth of new synapses
What brain regions are important for CC?
Cerebellum and the amygdala
Pavlovian conditioning/associative conditioning
pairing with a conditioned stimulus or CS (bell tone) with an unconditioned stimulus (meat) so that eventually the animal responds to the CS with the response intrinsic to the US (salivation) this is the CR
Associative learning/CC in Aplysia
In aplysia, pairing an air/water puff to the siphon with a tail or headshock, here the timing of stimuli presentation and pairings is what distinguishes conditioning from sensitization,
-The CS is soecific, so only innocous pressure to the siphon but not the head/tail will elict the response
What happens if you inhibit protien synthesis in animals trained in classical conditioning or a maze
No impairment in learning/memory 1 hr after training
Impairments evident if you test animals 24 hr after training
Long-term potentiation
Rapid onset, activity dependent, long-lasting change in synaptic strength, can be elicted in the hippocampus and to some extent in cortex.
LTP procedure
induced by high frequency stimulation (100Hz tetanus), transverse slices of hippocampus bathe in acritical cerebrospinal fluid
LTP what is stimulated?
Schaffer collaterals (projections from CA3) and record externally from CA1 field (population or field potential)
When stimulating schaffer collaterals…
See a negative response in extracellular recording of CA1 population
With stronger input/increase in tetanus number…
you see an enhancement of response (early/late LTP)
Mechanisms of LTP
NMDA receptors act as coincidence detector, expressed on the CA1 neurons
What do NMDA receptors do in LTP
Allow Ca2+ influx when pre/post synaptic cells are activated simultaneously
(coincidence of glutamate release/depolarization)
What does Ca2+ activate in LTP?
kinases, short and long term effects leading to potentiation of the synapse
Short-term
covalent modifications of pre-existing protiens
(phosphorylation of channels/receptors)
Long-term
CREB, nuclear transcription, changes in protein synthesis
AMPA receptor cycling in LTP
AMPA receptors are inserted into post-synaptic membrane
AMPA receptor cycling in LTD
Decrease of AMPA receptors into post-synaptic membrane
Where is polymodal information from association cortex sent?
To the entorhinal cortex and then to the hippocampus
Superficial layer of entorhinal cortex
projects to hippocampus, hippocampus projects back to deep layers of entorhinal cortex, and then back to superfical layers
Pattern seperation
Disassociation of similar scenes thought to occur at dentate gyrus
Pattern completion
memory retrival with pattern completion, occurs at CA3 level, due to recurrent connections between CA3 neurons.
CA1 monitor processing
recieves input processed by the indirect pathway and non-processed information directly from entrohinal cortex
Indirect pathway of CA1 monitoring
Denrate gyrus and CA3
Proximal dendrites recieve input from
DG/CA3
Distal dendrites recieve input from
entrohinal cortex
-Allows CA1 to act as a comparator
Hippocampal place cells
discovered through in vivo recordings in awake behaving rodents
Cordination of popilations of place cells…
Make up cognitive maps of the enviroment
Some cells show
metric/scaled representations of the enviroment
Hippocampus
critical for consolidation of memories, forming new long-term memories
Declaritive/spatial memory use..
The hippocampus
You can’t form new memories without…
the hippocampus
Cortex role in memory storage
storage of long-tetm memories; damage to certain cortical areas can cause retrograde amnesia
Striatum role in memory
Important for procedual memory; the striatum is apart of the basal ganglia
What is the striatum composed of?
Caudate nucleus/Putamen
If striatum is damaged how does that affect learning of tasks/skills?
Patient may remeber having learned the task before, but they will never improve on it
Cerebellum role in memory
regulating skeletal muscles, so it’s critical in classical conditioning that involves muscle responses
Patient H.M
bilateral exision of medial temporal lobes (removing hippocampus)
-Anterograde amnesia
-Procedual memory intact
Tracing shapes
procedual memory requiring the striatum
Morris water maze
Hippocampal dependent learning/memory (spatial naviagtion task)
Radial arm maze
spatial cues —> hippocamus dependent
light stimulus —> striatum dependent associative learning/memory