Hippocampal LTP Flashcards
what is the early evidence for LTP in the HPC
Bliss & lomo 1973
measured excitatatory post synaptic potentials in the neural pathway from the entorhinal cortex, to dentate gyrus to the perforant pathway by recording from granule cells and the amplitude and latency of granule cell population spike in anaesthetised rabbits while applying test pulses every 30 seconds. Crucially, occaissionally they would administer high frequency tetanus (200Hz)
following the tetanus there was greater EPSP for the same stimulus
suggests increase in synaptic transmission efficiency at perforant path synapses and granule cells more excitable
what is Hebbian (1949) learning
The cellular basis of learning involves strenghtning of a synapse that is repeatedly active when the post-synaptic neuron fires
“when an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change occurs in one or both cells such that cell A’s efficiency as one of the cells firing cell B increases”
Whitlock et al., 2006
Inhibitory Avoidance - demonstration of naturally induced LTP following learning event
Rats initially prefer the dark section of the chamber to the illuminated one, but this preference switches following administration of a shock to the foot in the dark chamber. This preference was demonstrated to persist after a 24 hour retention interval.
To see if recordings from electrodes strengthen following learning, electrophysiological analysis of synaptic in CA1 was measured by stimulating Schaffer collaterals with a multielectrode array to measures lots of different locations in CA1.
The average field EPSP doesn’t change following inhibitory avoidance training as compared to controls but between electrode variance increases
rather than the typical slight decrease in fEPSP following movement some channels show significant increase only in the inhibitory avoidance group which appears rapidly and persists through the session.
subsequent high frequency stimulation on the freely behaving animal resulted in HFS-induced electrical LTP that was inverse correlated with the magnitude of initial behavioural LTP such that it was not successful at inducing further LTP in channels where the EPSP already increased. This is suggestive of a common mechanism of the two processes (i.e. both are LTP). Moreover there was no uniform increase in fEPSP so this effect is not temperature dependent.
isolating synpatoneurons from the dorsal HPC and the usig immunochemistry with selective antibodies to look at AMPARs in post-synaptic membrane found an in increase in GluA1 and GluA2 in post-synaptic membrane of inhibitory avoidance group compared to controls that is rapid and transient (back to baseline by 2/3 hours). Dissociation between plasticity readout and memory readout.
Morris 1989
water maze
Manipulations that prevent HPC LTP should prevent HPC dependent learning (associative spatial reference memory)
Pharmacological blocking of NMADR with DL-AP5 impairs performance on a spatial reference memory watermaze task
But DL-AP5 rats successfully acquired visual discrimination task in the watermaze
what is the alternative explanation for why Ap5 mice were impaired on the Morris water maze
sensorimotor impairment
Cain et al., 1996
High correlation between performance and sensorimotor impairment
Watermaze (hidden and visible platform), alley swim, beam walk
Rats that do poorly on one measure do poorly on all
General sensorimotor impairment
AP5 showed 5-6’C drop in brain temp
NMDA may potentiate hypothermia and slow swim speed
Bannerman et al., 1995
Rats were administered intracerebroventricular AP5 or artificial CSF
if the rats are pre-trained on the watermaze task in a different laboratory the AP5 rats are able to learn the task and show the same search biases towards the quadrant associated with the platform, although their search latency is slower (consistent with minor sensorimotor impairment)
Same inhibition of LTP due to AP5 seen
Repeating this procedure with rats who have undergone targeted HPC lesions with ibotenic acid, sham-lesions or no-operation the HPC lesioned rats are unable to learn the upstairs maze
Thus expression of spatial learning is HPC dependent
Not due to stimulus transfer or procedural learning that the platform is a refuge
Rats received non-spatial pretraining and AP5 are still impaired (relative to controls and spatial training), however they are above chance so less impaired than with no training indicating that there are non-spatial components to this task
Thus acquiring this information usually requires NMDAR-dependent synaptic plasticity and the HPC is necessary for the expression of this learning
AP5 NMDAR blockade disrupts both spatial and non-spatial learning, possibly dependent on the interaction of different cerebral circuits
Tsien et al., 1996
NMDAR1 gene deleted exclusively in CA1 pyramidal cells (NMDAR1 CA1-KO mice)
CA1-KO mice display a selective and significant deficit in spatial memory because they are unable to develop a navigational strategy in the Morris water maze but they could perform nonspatial learning tasks that rely on simple association strategies
NMDAR mediated LTP in the CA1 is crucially involved in the formation of certain types of memory
Although slower latency on landmark task - worse on swimming to visible platform than controls, which you do not need HPC for
Not truly hippocampal specific as clear reduction of GluN1 levels in cortex within 2 months of mice being born (Fukaya et al., 2003; Rondi-Reig et al., 2006)
Bannerman et al., 2012
