Hippocampus, Memory and Synaptic Plasticity - L8 Katie Burgess

Why do we use rodent models?

Lab rats are small, easy to house, quick to learn.

Also have a relatively large hippocampus compared to the rest of their brain - easily identifiable

The Rat’s Hippocampal Network

1. Information enters the hippocampus through the dentate gyrus (DG)

2. Then travels through the CA3 region

3. And back out through CA1 region

DG → CA3 → CA1

Study by John O’Keefe investigating rat’s hippocampi

Identified place cells by placing electrodes in the CA1 region of the hippocampus.

He found that specific cells in the CA1 region will fire at really high rates when the rat is in a particular location - different cells for different locations (aka place cells)

• this is evidence for cognitive map.

What is the Morris Water maze?

pool of opaque water, with hidden platforms, given a minute to swim - used to test spatial learning in rats - usually rats get faster with each trial and spend more time in quadrant that had platform even when not there

Results for rats with hippocampal lesions in the Morris water maze:

Much slower to find the platform than controls (no surgery/ surgery but no lesion) -but eventually still learnt to find the platform by swimming a certain distance from edge of pool

How did Morris demonstrate the navigational impairment was due to hippocampal lesion and not just general cognitive impairment?

Placed a beacon above the platform to indicate where it was - hippocampal rats performed normally (object recognition was intact)

BUT when the beacon was removed, the hippocampal rats got worse.

AND in the probe trial (removal of entire platform), they swam aimlessly (not in the correct quadrant)

What is Hebb’s rule?

co-occurrence (both neurons firing) is a physiological necessity for learning and memory - cells that wire together fire together due to long term potentiation

Investigating Long-term potentiation (Bliss and Lomo, 1973)

1. Delivered low-intensity pulses to the perforant path neuron (pre-synaptic) and recorded activity in the dentate gyrus (post-synaptic). = original response baseline

2. Delivered 10 seconds of high-frequency potentiation and recorded much higher activity in dentate gyrus

3. Then delivered low intensity pulses again and found, still high activity in dentate gyrus. (even after a month)

2 properties of Long term potentiation:

1. Long-term

2. Requires co-occurrence (post and pre synaptic neuron both fire at the same time)

Normal Functioning of Neurons in Hippocampus

During normal functioning, glutamate (excitatory) is released from the pre-synaptic neuron and binds to an AMPA receptor on a post-synaptic neuron = leads to an influx of sodium ions (depolarisation)

Functioning of Neurons during LTP when a high frequency impulse arrives

During normal functioning, NMDA ion is blocked by the magnesium ion (Mg+ is attracted to the negative charge of the inside of the cell) = BUT when cell is depolarised the Mg+ ion is repelled. If glutamate binds to NMDA receptor, it allows for influx of calcium.

2 conditions for the NMDA receptor to allow an influx of calcium:

1. Pre-synaptic cell is firing = releases glutamate

2. The post-synaptic cell is firing = depolarisation

   → therefore, NDMA is a coincidence detector