Please enable JavaScript.
Coggle requires JavaScript to display documents.
BIO SCI N156 Lecture 17: Memory Modulation & Memory Reconsolidation…
BIO SCI N156 Lecture 17: Memory Modulation & Memory Reconsolidation
Memory modulation
Post-place learning injection into amygdala
NE: enhanced rat's retention of platform location
Propranolol: impaired retention
Post-inhibitory avoidance training [with strong foot shock] injection into amygdala
Propranolol: impaired retention
NE: enhanced rat's retention of the foot shock
Model: experience has two independent effects
Initiate the acquisition and storage of the memory trace
Can activate the release of adrenal hormones that can modulate the processes that store the memory
Memory consolidation processes
Stimulation of the BLA
Inject amphetamine into amygdala following training on place-learning lesion of Morris water maze
Enhanced retention performance
Hippocampus: critical for place learning
Inject amphetamine into amygdala
following training on visible platform task
Improved retention performance
Caudate: critical for visible platform task
This coupling of experiments is a
double dissociation
Conclusion: BLA is a "promiscuous" modulator
Can modulate memories requiring different brain systems
BLA modulates memory consolidation
Infusions of amphetamine into BLA enhance memory consolidation processes outside of the BLA
Activating BLA after training enhances memory consolidation
Inactivating BLA prior to testing does not affect memory retrieval
BLA not needed for memory retrieval
Time-dependent stabilization
Disrupt or facilitate specific cellular processes during consolidation period, impair or enhance memory at testing [respectively]
Epinephrine
Does not cross BBB
Model for its effect on brain processes
Released from adrenal medulla
Binds to adrenergic receptors on vagal nerve
Vagal nerve releases glutamate on neurons in solitary tract nucleus (NTS)
NTS neurons release glutamate onto neurons in locus coeruleus
Releases NE into BLA
Disrupting any component of the model will prevent arousal from enhancing memory
Lesions of vagus nerve, NTS, LC, or BLA block memory modulating effects of systemic epinephrine injections
Arc translation experimental design
Procedure:
Implant cannula into the BLA of rats
Train on inhibitory avoidance task
Inject with a beta-adrenergic agonist (clenbuterol) or lidocaine
Either sacrifice rats or test on IA task
Hippocampus brain tissue sampled for Arc
Results:
Lidocaine injection group: lower levels of Arc
Clenbuterol group: higher levels of Arc
Suggests that BLA modulates memory be influencing the level of Arc in the hippocampus
Locus coeruleus
Major source of norepinephrine (NE) to many brain regions
Project widely throughout the brain
When NE from LC is released into hippocampus, PKA is activated and phosphorylates GluA1 AMPA-R subunit
Facilitates trafficking of GluA1s into dendritic spine, increases memory strength
Emotional stress dives phosphorylation of GluA1 receptors via NE in brain
NE regulation of AMPA-R trafficking
NE acts in time-dependent fashion to facilitate LTP
Timing of NE on LTP identical to timing needed for post-training epinephrine to facilitate mem. consolidation
Time dependence of NE in GluA1 phos. matches LTP of above
Design:
Pre-exposure in chamber: no shock
Next day: placed in chamber for <5 sec., foot shocked
Next day: testing for context-fear memory
Results: with weak conditioning, WT mice, but not GR1AA mice (with mutation blocking GluA1 phos.), showed enhancement of memory by epinephrine
Suggests that epinephrine facilitates memory formation via GluA1 phos. during learning
Glucose mobilization/bioenergetics
Bioenergetics: flow of energy in cells
Glucose: primary source of energy
Enters brain via cerebral vasculature
Arousing event activates adrenal medulla to release epinephrine into blood stream, binds to liver cells
Liver secretes glucose into blood, enters brain
Systemic injections of epinephrine or glucose influence memory strength in dose-dependent manner
Glucocorticoid stress hormone release
Stress hormones: epinephrine and glucocorticoids
Made by diff. regions of adrenal gland
Epinephrine activated quickly via neural route
Glucocorticoids activated more slowly, stay elevated for longer
Bind to GR and MR receptors
Affect:
Postsynaptic function: affect signaling for rapid events in postsynaptic cell (e.g., PKA activation); takes longer to manifest, but longer lasting, effects
Presynaptic function: facilitate NT release; rapid effect
Gene transcription: regulation of stress response genes; longer to manifest, but longer lasting, effects
Cortisol
Delayed response (peaks 15-30 min. after stressor)
Chronic stress hormones are bad for brain
Synaptic loss, impairment of neurogenesis, neuronal loss
Impaired memory processes
Mild and temporary increases in stress hormones can enhance memory processes
NE and glucocorticoids work in concert to influence memory
Facilitate rapid early induction
Facilitate the maintenance of the synaptic strength
PTSD
Hypothesis: PTSD occurs when memory modulation goes awry
Stress makes stronger memories, which are then re-experienced frequently
Drives stress and makes the memories stronger yet through many iterations: kind of feed-forward loop
Possible treatments
Beta-blockers: administer the drug during the behavioral therapy, block effect of epinephrine and NE
Behavioral treatment: discuss triggering event, use virtual reality to immerse person back in experience
Re-wiring the circuit so that the memory is not coupled with the stress hormone release
Retrieved memory
Under some conditions, retrieving or reactivating a consolidated memory can return it to an active, labile state