Synaptic Plasticity in Learning and Memory Flashcards
what types of memory are there?
explicit (declarative) and implicit (nondeclarative - procedural, skeletal musculature, emotional response)
what is learning?
the response of the brain to environmental events
involved adaptive changes in synaptic connectivity which in turn alters behaviour
what did Hebb hypothesise?
if activation of cell assembly persists for long enough, consolidation occurs by ‘growth process’
what is the cell assembly?
internal representation of an object consists of cortical cells with are activated by it
what is the relevance of the cell assembly?
reciprocal connections are more effective - neurons that fired together, wired together
even if fraction of cells are activated by later stimulus, strengthened connections cause whole assembly to become active again
rules of synaptic modification
- neurons that fire together, wire together
- neurons that fire out of sync lose their link
strengthening and weakening synaptic connections in the brain provide means by which learning occurs and memories can be formed
what is associative long term potentiation?
if activity of strong synapses is sufficient to trigger an action potential in the neuron, the dendritic spike will depolarise the membrane of dendritic spines
which cells have been most studied in regards to LTP?
hippocampal neurons
shape an anatomy means pathway can be easily distinguished and recorded electrophysiologically
how do hippocampal neurons generate EPSP great enough to fire action potential?
different sensory inputs from cell A and B (sight and smell)
when A and B are activated together, coincident EPSPs may stimulate sufficiently to cause AP
is association is made repeatedly - cells A and B simultaneously fire onto hippocampal neuron, synapses are strengthened
strengthening synapses of A and B means they are able to individually able elicit APs
LTP is temporal
summation of inputs reached a stimulus threshold, leading tin induction of LTP
LTP is associative
simultaneous stimulation of strong and weak pathways induces LTP in both pathways
coincidence detection
‘cells that fire together wire together’
LTP is specific
LTP at one synapse is not propagated to adjacent synapses (input specific)
how have hippocampal neurons been studied for LTP?
high frequency electrical stimulation (HFS) of perforant pathway
axons from entorhinal cortex pass to dentate gyrus
cells from dendate gyrus recorded
subsequent EPSPs after HPS have increased amplitude
one HFS: lasts hours
multiple HFS: LTP lasts days/months
what happens at the synapse at resting potential?
glutamate is released onto inactive cell
AMPA receptor is activated to create EPSP
NMDA receptor is blocked by Mg2+
depolarisation from AMP activation not enough to expel Mg2+
what happens at the synapse during depolarisation?
glutamate is released onto active cell (depolarised membrane)
AMP receptor is activated
Mg2+ block on NMDA receptor is relieced
NA+ passes through AMPA and NMDA channels, and Ca2+ through NMDA channel
Ca2+ leads to long term potentiation
how does Ca2+ affect LTP?
Ca2+ enters through NMDA receptors and activates protein kinase C and CaMKII
leads to phosphorylation of existing AMPA receptors (active state)
stimulates insertion of more AMPA receptors into membrane
more AMPA = more chance of depolarisation, more likely NMDA is unblocked, more likely for AP to fire
what role does CaMKII play?
molecular switch
Ca2+ entry activates CaMKII
CaMKII = autolytic, phosphorylates self
then is constitutively active (doesn’t require Ca2+)
maintains phosphorylation, insertion of AMPA receptors etc, after depolarising stimulus has receded
can maintain increased excitability of neuron for minutes/hours
presynaptic effects in LTP
postsynaptic neuron can feed back to presynaptic by retrograde transmitter (NO)
Ca2+ through NMDA channel activates nitric oxide synthase
NO diffuses from site of production - activates guanylyl cyclase in presynaptic terminal
produces second messenger - cGMP
leads to increased glutamate response from synaptic button
late phase LTP
long lasting LTP (days months)
protein synthesis is required
stages of memory formation
acquisition
consolidation
recall
what is protein synthesis necessary for?
consolidation
when protein synthesis inhibitors injected post-recall, recall is inhibited
CREB protein
cAMP response element binding protein
involved in long term memory formation
activated by phosphorylation by many kinases (PKA, CaMKII, etc)
regulates gene transcription
what is early phase LTP?
lasts a minute-hour can be explained by: - actions of Ca2+ through NMDA receptor - subsequent enhancement of AMPA receptor efficiency - presynaptic events
what is late phase LTP?
lasts hours, days or months
requires new protein synthesis - can involve morphological changes and establishment of new synapses
Ca2+ activated transduction cascades
what are Ca2+ activated transduction cascades?
activate new protein synthesis from dendritically localised mRNAs
filter back to cell body to stimulate new gene transcription, protein synthesis and recruitment of new proteins to the synapse
what is LTD?
long term depression
opposite to LTP
low frequency stimulation causes decrease in EPSP amplitude on further stimulation
how does LTD occur?
NMDA dependent processes
AMP receptors are de-phosphorylated and removed from membrane
pronlonged low level rises in Ca2+ activate phosphatases rather than kinases
LTP and LTD reflect the bidrectional regulation of…
phosphorylation
number of postsynaptic AMPA receptors
do changes in synaptic activity lead to learning?
+ proof
NMDA receptor activity in hippocampus is essential for LTP and spatial learning
AP5 (NMDA receptor antagonist) infused into rat hippocampus
blocked hippocampal LTP
blocked learning in Morris-Water Maze
are studies on animals relevant?
huan infertemproal cortex removed during surgery but maintained in vitro
high frequency stimulation produced LTP
low frequency produced LTD
which drugs can effect learning and memory?
alcohol
benzodiazepines
cholinergics/anticholinergics
effect of alcohol
NMDA receptor antagonist
directly blocks normal LTP processes - hence blackouts/amnesia caused by drinking
disrupts hippocampal rhythms and short term memory
Korsakoff’s syndrome/psychosis
associated with chronic alcoholism and associated nutritional deficiency
symptoms:
- loss of recent memory
- tendency to fabricate accounts of recent events (confabulation)
effect of benzodiazepines
indirect agonist of GABA(A) receptors
binding increases receptor affinity for GABA
increases frequency of channel opening anxiolytic and hypnotic drugs
side effect = anterograde amnesia
where can acetylcholine projections be found?
basal forebrain bundle:
- medial septum to hippocampus
- basal nucleus to cortex
septum to hippocampus projection regulates theta waves
what is scopolamine?
muscarinic receptor antagonist
suppresses theta waves
impairs spatial learning
effect of acetylcholinesterase inhibitors in Alzheimer’s patients vs healthy brain
Alzheimer’s: boost cholinergic function
improves memory impairments
in healthy brain: controversial as to memory improvement but may increase attention
other learning processes using LTP or similar mechanism
activity dependent synaptogenesis (development)
motor learning, eg riding a bike
