consolation and synaptic plasticity - week 2 Flashcards
timescales of memory
memories can persist for different lengths of time depending on underlying mechanism
memories can be localised to specific areas of the brain, take time to stabalise and are likely to be supported by synaptic plasticity
- pavlovian fear memories in the amygdala
memories can be supported by decreases in synaptic strength
- motor memories in the cerebellum
visual memory
can be separated into 3 stages
iconic
short term memory
long term memory
iconic memory
less than 1 second
likely to result from brief after images in the sensory neurons of the retinal surface in the eye
demonstrated with the sperling array
short term memory
retention of information over a period minutes to hours
poorly defined concept
generally thought that the biological mechanisms of s-t memory commonly include sustained neural activity
- persistent neural activity can sustain STM
in monkeys
- electrophysical recordings showed that the activity of neurons in the visual association inferior temporal cortex which were sensitive to a particular complex visual stimulus actually outlasted the presentation of the stimulus
long term memory
can last up to a lifetime (24 hrs)
depends on specific areas within the temporal lobe
fear conditioning
type of pavlovian conditioning
includes the formation of an association between a previously meaning stimulus and an aversive outcome
subsequent exposure to the now fear-conditioned stimulus results in fearful behaviour
fear conditioning - what is the main brain area implicated
amygdala
encoding long lasting memories
persistant neural activity sustains STM eventually this dissipates yet the memory remains intact for much longer
notion that STM is stabilised into a LTM may be inaccurate
- certain studies show that is STM is impaired LTM still forms
- so perhaps the mechanisms of LTM are triggered directly by the learning event in parallel with sustained neural activity
what distinguishes LTM and STM
differing dependence upon the synthesis of new proteins
mechanism for memory consolidation
what shows synthesis of protiens is needed for memory consolidation
anisomycin - prevents protein synthesis
can be infused directly into brain of rats at levels that almost completely prevent the synthesis of any new protiens for several hours
intra-amygdala infusion of anisomycin before or soon after pavlovian conditioning selectively disrupts LTM while leaving STM intact as shown in fear conditioning
also increased gene expression triggered by learning
- reasonable to suggest that specific protiens encoded by their up regulated genes might be required for consolidation
mechanism for memory consolidation
what protein
the activity - related cytoskeletal - associated protein (Arc) is simply up regulated in the amygdala following pavlovian fear conditioning
when synthesis of arc is selectively inhibited in the amygdala, the consolidation of the fear memory impaired
mechanism for memory consolidation
mechanism that translates behaviourally induced electrical signals in brain into gene expression
one of the direct regulators of arc expression is the ERK/MAPK signalling pathway
mechanism for memory consolidation
ERK/MAPK signalling pathway
this pathway consists of a series of kinases
these are protein enzymes that function to phosphorylate other protiens
this causes their enzymatic function to be activated
leading to the activation of further downstream mechanisms in the pathway
the same study that the upregulation of arc following fear conditioning also showed that this upregulation was dependent upon ERK/MAPK signalling
- as expected the inhibition of ERK/MAPK signalling also impairs the consolidation of fear memories in the amygdala
mechanism for memory consolidation
NMDA receptor
glutamatergic receptor
upstream of ERK/MAPK pathway the primary cell surface receptor involved in learning in the NMDA receptor
heavily implicated in learning with links to ERK/MAPK pathway
mechanism for memory consolidation
NMDA receptor - evidence
direct infusion of NMDA receptor antagonism AP-5 into the amygdala blocks the acquisition of fear conditioning
blocks LTM
also impairs STM
- suggest NMDA receptor is critically involved in memory acquisition
- divergences downstream mediating STM and LTM
synaptic plasticity
alteration in the strength of a synapse
long term potentiation
persistent enhancement of postsynaptic response
long term potentiation
demonstation
by lomo in hippocampus of anaesthetised rabbits
long term potentiation
basis observation by lomo
if one of the pathways into the hippocampus (the perforant pathway terminating in the dentate gyrus) was stimulated at a high frequency
the subsequent response to a test stimulation was increased
importantly this potentiation lasted up to 10 hours after stimulation
- much longer than any sustained activity in studies of visual STM
synaptic understanding of pavlovian conditioning in the amygdala to lomo
3 main differences: species
behavioural on rabbit
most pavlovian conditioning on rodents
synaptic understanding of pavlovian conditioning in the amygdala to lomo
3 main differences: area
those on rodents have concentrated on hippocampal LTP
not easy to explain how synaptic potentiation between 2 hippocampal neurons gives rise to the complex spatial and concious memories that are thought to depend on hippocampal processing
synaptic understanding of pavlovian conditioning in the amygdala to lomo
3 main differences: associative nature
the original LTP observed was non-associative (induced by activity in a single input pathway)
contrats associative LTP (depends on co-activated of two inputs) that is thought to underpin associative learning
associative LTP may be able to explain pavlovian conditioning because it involves 2 neural pathways
LTP and memory?
similarites between LTP and memory consolidation
stong evidence that LTP is a mechanism of memory
(distinction similar to LTM and STM)
LTP and memory
demonstration
know that there is synaptic plasticity in the amygdala of rats and mice
- conditioned rats to associate a tone with an adversive footshock then measured both behavioural fear and electrical activity in the amygdala elicited by the tone
the electrophysical response in the lateral amygdala was substantially potentiated after conditioning, and if the conditioning parameters induced a behavioural memory
- unpairing tone and footshock = no synaptic plasticity
LTP and memory
underlying mechanism?
while the demonstration of behaviourally induced synaptic potentiation strongly suggests plasticity mediates longer term memory
doesnt necessarily follow the associative LTP in the amygdala is the underlying mechanism
LTP and memory
technological advances
enabled us to demonstrate directly the associative nature of amygdala LTP
can now experimentally activate specific neurons in the amygdala and if this is done at the same time as the presentation of the tone it is possible to artifically induce conditioned fear in a rat that has never been exposed to footshock
therefore consolidation is linked to synpatic plasticity
does LTP require protein synthesis
yes
stimulation in amygdala upregulated the expression of arc
does LTP require NMDA receptors
yes
long term depression
persistant reduction of postsynaptic response
long term depression
- why does it happen
due to low frequency stimulation
can LTP and LTD co exist
yes
both can lead to increased responses
depends on where in the circuit
where is LTD most commonly associated with ?
cerebellum
linked with motor form of learning —> DEBATED
LTD at excitatory
decrease
LTD at inhibitory
increase
LTP at excitatory
increase
LTP at inhibitory
decrease
