Hippocampus, Memory and Synaptic Plasticity

Hippocampus, Memory and Synaptic Plasticity

1. fMRI: Hippocampal role in Spatial and Episodic Memory

   • If the hippocampus is damaged, there is severe disruption to spatial memory
   • Spatial Memory: The ability to retrieve the representation which specifies where you are, and where other items are in relation to you based on past experience
   • fMRI can identify brain activity
   • Burgess et al 2002: brains imaged whilst p's performed a task whereby ps had to navigate around a town - in doing this, they met items (books, fruit and veg etc.) and certain people in certain locations. Hippocampus became predominately active when individuals were asked to encode info about the spatial location about either the items or people that they had met. Supports previous ideas about lesions to hippocampus impairing spatial memory. It was the right hippocampus that became the most active (still unsure why). Also tested peoples ability to encode episodic memory - left hippocampus that showed activation.
     • Showed that there are differences in the sides of the brain in how the hippocampus acts: Spatial memory = right side, Episodic memory = left side. Reasoning for this is unclear.
   • Sherry & Duff 1996: Food storing birds (e.g. Srub-Jay) collect seeds, store and bury them in distinct locations within their home environment. They go back to these locations and retrieve the seeds in winter - using spatial memory. Looked at brains of birds: food storing birds have. a larger hippocampus than non-food storing birds. Is this because they use the hippocampus more?
   • If there is plasticity in gross anatomy (birds) we may expect to also see this in humans
     • Maguire et al 2000: To what extent might experience on a job requiring spacial memory influence the anatomy of the hippocampus? Used MRI imaging to look at structure and volume of hippocampus in taxi drivers and controls. Taxi drivers show experience related changes in size of hippocampus: posterior larger than controls; anterior smaller than controls (to accommodate for increase in volume of posterior H.). This increase in volume was correlated with time as a taxi driver.
     • Maguire et al 2006: which of two landmarks is closer to a third? Taxi drivers had better recollection of landmarks around London than bus drivers. When ps asked to judge relative distances between areas/ regions of London, taxi drivers also performed better than bus drivers. These 2 tests were consistent with the idea that taxi drivers have better, more detailed, spatial memory for distinct landmarks in London. Also tested ps on the Rey-Osterrith Figure (expose p to figure, and then ask them to draw it as accurately as possible from memory). Taxi drivers considerably worse than bus drivers - spatial info about London was really good but spatial memory on this figure was poor: there may be a cost to having a big rear end of hippocampus - the front of hippocampus suffers, and other types of spatial memory get worse due to this anatomical plasticity.

2. Location and Anatomy of the Rat Hippocampus

   • There is one major bundle called the 'fx' which projects to different areas of the cortex and subcortical regions.
   • In terms of anatomy, there is a very distinctive 'v' shape forming the hippocampus (in rats)
   • There are 2 distinctive features of the hippocampus in rats:
     • 'Inner V' - The Dendate Gyrus: receives most of the info going into the hippocampus from the cortex. It is the major input pathway into the hippocampal formation. There is a tai-synaptic loop whereby info whizzes around the cortex.
     • The Perforant Path: major input pathway from the cortex. It is a bundle of axons in the cortex that come together and project into the Dendate Gyrus.
   • O'Keefe & Dostrovosky (1971): In the hippocampus, there are things called place cells which only fire rapidly when the rat is in a specific location. Put multiple electrodes into the CA1 and you can find individual neutrons that will only fire in specific locations. Place cells do not show any other behaviour - they do not react to anything else. These cells are showing plasticity - they only fire rapidly when the animal is in a specific location.

3. Spatial Memory in Rodents: Morris Watermaze

   • Spatial memory task - bowl of opaque water (2-3m in diameter). There is a platform hidden about a cm below the surface. The animal cannot see the platform and is trained to find it on the basis of cues - they were to form a memory based on their representation of the external, spatial environment about where the platform is.
   • Looked at effects of lesions of the hippocampus, control lesions (cortical lesions) and controls
     • Place navigation: rats given no clues as to where the platform is - platform defined by where it is in spatial environment.
     • The lower the latency, the better the animals were at finding the platform
     • The hippocampal lesioned rats learned that the platform is located in a specific distance - not the spatial location of the platform
     • Cue navigation: placed a cue by the platform, and the hippocampal lesioned rats were really good at finding the platform
     • Place navigation II: as soon as you take the cue away, the hippocampal lesioned rats went back to the pattern that they showed before
   • Key evidence that the hippocampus is essential in rodents for spatial memory

4. Donald Hebb

   • When an axon of cell A is near enough to excite cell B and repeatedly takes part in firing, some growth process or metabolic change takes place in one of both cells such that cell A's efficiency as one of those cells firing B is increased: "cells that fire together wire together".
   • Tim Bliss tested this:
     • Recorded activity of cells in hippocampus when we send artificial patterns of stimulation in it: placed a stimulating electrode in the Perforant Pathway. In turn, synapses will make connections with the cells in the Dentate Gyrus - he was recording cells in the Dendate Gyrus. Measured Speed or which neural activity occurred and the activation of an action potential.
     • Originally was sending single pulses at a time. Accidentally hit a switch that sent bursts of stimulation at a time. When he went back to sending single pulses, the measured of activity ion neurons suddenly increased
       • Speed increased: some type of change had happened that the efficiency by which the pulse from the Perforant Pathway activated neutrons in the Dentate Gyrus had increased. This change in the wave form lasting a long time, it is likely that this change of efficiency could be permanent - there is synaptic plasticity in the brain.

5. Induction of Long-Term synaptic potentiation (LTP): required NMDA receptors

   • The Perforant Path input releases glutamate when it is stimulated. The glutamate is picked up by two types of receptors: AMPA and NMDA.
   • When there is a massive release of glutamate, so many AMPA receptors are stimulated that the membrane becomes depolarised. When depolarisation occurs, the NMDA receptors become unblocked. The channel now sucks in calcium from outside of the synapse, downstream causing new AMPA receptors to be inserted into the post-synaptic membrane.
     • The AMPA receptors are effectively the 'ears' of the membrane, listening out for glutamate. Now there are more AMPA receptors, there is higher sensitivity to glutamate signals

6. Morris et al 1986

   • Used a drug (AP5) that selectively blocks NMDA receptors - they cannot function normally so will not receive glutamate signals. AMPA receptors are not effected.
   • Gave animals AP5 and looked at the amount of optical learning in the Morris Watermaze
     • Control animals acquired info about where the platform was really quickly
     • Animals that received AP5 acted in the same way as those who received Hippocampal Lesions. - showed no spatial memory for the platform
   • Spatial memory, supported by hippocampus, is impaired when you block the NMDA receptors.
   • Control test: AP5 did not impair visual discrimination task
   • Donald Hebb was right: synaptic plasticity underlies learning and memory. If you block synaptic plasticity, particularly via NMDA receptors, you block spatial learning and memory.