Encoding Pt 2 - Hippocampus and Long Term Memory

Memory retrieval

Parahippocampal and rhinal cortices → Hippocampus

What structure is shown in the image?

Hippocampus

Medial Temporal Lobe - Anatomy and constituents

Parahippocampal and perirhinal are connections between Association cortices (all 3) and hippocampus

Removal of the medial temporal lobe

Results in severe anterograde amnesia (Clive Wearing)

What does the hippocampus do?

Form declarative/explicit memories

• Ultimately ‘stored’ in the cortex

Tells you where you are in space

• Spatial memory/learning

Often lost early in Alzheimer’s

Active site of neurogenesis

Multiple sub-regions

Encoding patterns

Pattern completion

• Recognising something from a partial representation

Pattern Separation

• Learning to distinguish between similar

The hippocampus is very important for both

Not just for visual memories

Neuronal Signals

Electrical signal

• Travels along neurons as an ‘action potential’

Chemical Signal

• Travels between neurons as neurotransmitters

Excitatory neurotransmitters

• Increase probability of target neuron firing action firing action potential

Inhibitory neurotransmitters

• Reduce probability of target neuron firing action potential

What could a ‘code’ look like?

• Which neurons fire

• What causes them to fire

• How long they fire for

• Where they project to

• How many other neurons they are connected to

• Numbers/types of neurotransmitter receptors

What is Hippocampal indexing?

• The basis for ‘retrieval’

• Pattern completion

• Pattern separation

Hippocampal indexing

Pattern of neuronal activity from cortex activates a specific subpopulation of neurons in CA3

• These are densely, reciprocally, connected

Partial input (part of the pattern) - activates the whole group of CA3 neurons

• The connections between this group can be modified, for example when new information is learned

What is synaptic plasticity?

The cellular basis for learning and memory

Action potentials

1. Presynaptic neuron releases neurotransmitter

2. Enough ligand-gated channels open

3. Membrane reaches the threshold

4. Action potential will fire

Long-term potentiation definition

Frequent firing strengthens synapses

Long-term potentiation

Brief, intense firing by presynaptic neuron

• Abundant glutamate release

This causes changes in post-synaptic neuron

• Opens NMDA-type glutamate receptors

• Increases expression and insertion of AMPA-type glutamate receptors

• (other changes as well)

Strengthens the synapse

Increases the likelihood that neurons fire together

Changes are long-lasting

• Calcium influx prompts gene expression

Happens across the brain

• Best understood in the hippocampus

• Synapse between CA3 (Schaffer collaterals) and CA1 (Pyramidal cells)

Long-term Depression

Connections between neurons become weaker

Prolonged, low-intensity firing of presynaptic neuron

• Pre and postsynaptic neuron do not then ‘fire together’

Multiple cellular mechanisms

• Decreased expression/insertion of postsynaptic AMPA receptors

• Decreased presynaptic glutamate release

Also occurs across the brain

Not as well understood as LTP

From Synapse to code to memory

• One theory is that the ‘code’ is a pattern of firing of a specific group of neurons in a specific hippocampal region (CA3?)

• Firing pattern in association cortices activates that specific group - partial firing still activates full group

• The members of the group, and their firing pattern, can be modified by LTP and LTD - Allows for two distinct groups to be formed as part of pattern separation

• Directly linking LTP/LTD to memories is hard to do

Boosting Memory

• Eat glutamate?

• Stimulate NMDA and AMPA glutamate receptors?

• NMDA and AMPA receptors are everywhere

• Systemic stimulation can cause seizures

• Too much glutamate is excitotoxic and a major mechanism of cell death

Types of Spatial Representation

• Allocentric (non-egocentric)

• A map of the environment

• object-to-object

• hippocampus

Egocentric

• Where am I in the environment

• Me-to-object

• left/right, up/down etc.

• posterior parietal cortex and prefrontal cortex

Place Cells

Pyramidal neurons in hippocampus (CA1 + CA3)

Activated by allocentric environmental cues

• Visual, olfactory, other senses

Also activated by ‘replay’ of cues (thinking about the map)

Encode a ‘place field’

• Field is plastic - can change

Some are spatially oriented

• (front, back, etc)

Other navigational neurons

Head position cells

• Subiculum

• Fire when oriented towards a specific direction

Border cells

• Place cells that are specifically activated by barriers

Reward-place neurons

• learn about a reward in a particular place. Not value of rewards (happens in Orbitofrontal cortex), or place, but connection between the two

• Bringing together where it is and what it is, in the same network

Grid cells

Entorhinal cortex

Hexagonal map

• Only requires one co-ordinate to change location, compared to Cartesian (X-Y) mapping

• Adjacent grid cells map adjacent grid

Dead reckoning or path integration

• Calculating current position relative to a previous position

• Distance travelled, speed, direction