Learning and Memory Flashcards
Learning
The brain’s response to environmental events, involving adaptive changes in synaptic connectivity that alter behaviour.
“Cells that fire together, wire together”
i.e. when one neuron is sufficiently near another neuron to excite it and repeatedly does so, growth processes/metabolic changes occur to increase the efficiency of that neuron
Learning occurs through the strengthening and weakening of synaptic connections
Process:
- initially, individual input (e.g. grandma smell) not strong enough to stimulate hippocampal neuron
- if repeated associations made, synapses of A and B onto the hippocampal neuron are strengthened
- so individual input is now strong enough to stimulate hippocampal neuron (which stimulates neuron B - e.g. grandma image)
Long-term Potentiation (LTP)
Mechanism underlying synaptic strengthening; most early studies on hippocampus as shape/anatomy means easily distinguishable + recorded pathways.
high frequency stimulation (e.g. 1 x 100Hz; 100 times in a second)
- Temporal; summation of inputs reaches a stimulus threshold that leads to the induction of LTP (e.g. repetitive stimulation)
- Input specific LTP at tetanised pathway; does not affect adjacent synapses
- Associative; simultaneous stimulation of strong and weak pathway induces LTP at both pathways (spatial summation)
Studying LTP (rat task…. /torture)
Morris water maze
used to test spatial learning and spatial memory
- Hidden platform in large arena of water; rat placed in the water, moves around randomly (trying to escape) and eventually finds platform.
- Acquisition trials: repeat with platform in same location, rat finds platform faster each time
- Expression trials: remove platform completely, measure time spent in target vs nontarget quadrant
rat with a lesioned hippocampus does not learn, takes same amount of time as it did in the first trial (random searching)
role of NMDA in LTP
Normal neuronal transmission
* glutamate released into synaptic cleft
* binds to AMPA, depolarisation
* binds to NMDA, no effect because of Mg ion block
Depolarised postsynaptic membrane
* Mg ion block ejected from NMDA
* sodium and calcium ions flow into postsynaptic neuron (much bigger EPSP than AMPA because calcium boost; x2 positive charge)
Morris Water Maze evidence
* injected NMDA antagonist into hippocampus
* spent equal time in target and non-target quadrants (did not learn task, as though no hippocampus) - whereas saline injection spent more time in target quadrant
* = NMDA activity in hippocampus important for spatial learning
Change in AMPA receptors
* Entry of calcium ions into postsynaptic neuron activates CaMKII, which
* phosphorylates existing AMPA receptors, increasing efficiency (e.g. stay open for longer)
* stimulates insertion of new AMPA receptors into the postsynaptic membrane
* = same amount of glutamate causes larger EPSPs
CaMKII
* molecular switch
* Ca ion causes conformational change (opens up) so can start phosphorylating proteins
* autophosphorylation; phosphorylates itself so can remain open without requiring Ca ions
* therefore keeps phosphorylating after depolarising stimulus recedes; can maintain increased excitability of neuron for minutes to hours
Presynaptic events
* Ca ions through NMDA channel activate nitric oxide synthase (converts arginine to nitric oxide; a soluble gas acting as a messenger)
* NO diffuses from postsynaptic terminal to neighbouring presynaptic terminals, where they activate guanylyl cyclase
* Guanylyl cyclase produces second messenger cGMP
* This signal transduction cascade causes greater glutamate release from the presynaptic terminal
Late phase LTP
Requires protein synthesis
we know this because protein synthesis inhibitors prevent consolidation of long-term memories and LTP; when animals undergo training, consolidation and recall tests, if a protein synthesis inhibitor is injected post-acquisition (post-training) it inhibits recall, which is necessary for consolidation
CREB trancription factor is phosphorylated by kinases (such as CaMKII), which activates it and makes it transcribe genes more efficiently.
early vs late stage LTP
early phase
* lasts minutes to hours
* explained by actions of Ca2+ through NMDA receptor, subsequent enhancement of AMPA, other presynaptic events etc.
late phase
* lasts hours, days or months
* requires new protein synthesis
* can involve morphological changes and creation of new synapses
Long Term Depression (LTD)
weakens synapses
low frequency stimulation (e.g. 100 x 1Hz; 1 time a second for 100 seconds)
decrease in EPSP amplitude when further stimulation
- NMDA dependent process
- AMPA receptors dephosphorylated and removed from membrane
- because low level increases in Ca2+ activate phosphatase, not kinase
Physiological processes producing LTP
tetanic stimulation is an artificial process done in a lab
Theta rhythms in hippocampus accompany spatially oriented behaviour such as running, head movements etc.l play a role in synchronising activity in different brain regions
Stimulation of neuron at peak of theta rhythm = LTP
at trough = LTD
disrupting theta waves causes deficits in learning tasks similar to those caused by hippocampal lesions
Manipulating LTP
Genetically
* increased amount of particular type of NMDA receptor (high functioning; when activated, more Ca2+ through)
* Tang et al. (1990) found it enhances LTP in mice - used Morris Water Maze task, transgenic mice have quicker rate of acquisition than wide-type mice
Age
* decreased acquisition in MWM
* decreased LTP
* decreased expression of NMDA receptors
Enrichment
* enhanced acquisition in MWM
* potentiated LTP
Can enrichment reverse enrichment effects?
Aged mice in impoverished environment show greater deficits in spatial maze task than aged mice in normal or enriched environments
= neuroplasticity
Neuronal circuitry of conditioned fear (final flashcard to fill in)
