Place cells and memory 23/4 Flashcards
Define place cells
Hippocampal pyramidal CA1 and CA3 cells which become active in specific places - known as their environmentall specific place field. Populations of place cells co-activate in these places.
They are a spatial memory system, showing discrimination and LTP. They underpin the spatial element of episodic declarative memory
What is Hebbian Cell Assembly?
It is a pattern of response that has become auto-associated.
I.e., An input that repeatedly gives rise to a pattern of response results in any one part of the pattern giving rise to the other parts.
Auto-associated patterns are also known as engrams
It is set up by Hebbian Plasticity (cells that wire together fire together).
What are sharp wave ripples?
They are hippocampal neural patterns. SPW (sharp waves) are large amplitude negative polarity deflections in CA1 due to synchronous depolarisation of a large number of pyramidal cells. This is trigged by the synchronous firing of CA3 pyramidal cells. They are often associated with ripples in the CA1 pyramidal layer.
They occur during resting states such as non-REM sleep, stillness and eating. They are thought to consodilate memory by reactivating and potentiating synaptic connections that store recently learnt information.
What is the Charles Buzaki two step memory formation?
- Labile memory traces. The learning event causes a transient change in synaptic strengths in CA3, where the information is being stored. These are formed during the encoding phase.
- Long lasting memory trace. During ‘consummatory’ behaviours such as sleep, resting and eating, slow wave ripples (SPW-Rs) occur. The synapses activated by learning (during theta waves) are potentiated by the repetitive SWR. Alongside this, the information encoded in the hippocampus is transferred to the neocortex. This is thought to occur because SPW-R results in the discharging of cortical populations of neurons important for memory. This is the consolidation phase.
What are the two major states of hippocampal activity?
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Large irregular/sharp-wave/ripple (SPW-R).
Occurs during slow wave sleep and quiet wakefulness -
Theta (regular slow wave)
Occurs during motion, attentiveness and rapid-eye movement
What are theta waves?
It is a sinusoidal osscilating frequency pattern of neural activity in the hippocampus. It results from dipoles of excitatory input and inhibitory input. Entorhinal cells input excitatory stimualtion to the dentate gyral cells and pyramidal cells. The medial septum inpuuts inhibitory stimulation to pyramidal cells.
These inputs provide periodic subthreshold stimulation coherently across a wide range of hippocampal cells. It increases the signal to noise ratio by keeping the cells active below threshold, and also allows small inputs to trigger action potentials.
Why do CA3 neurons allow for pattern completion?
CA3 neurons have many recurrent projections, resulting in every CA3 neuron being connected to 2% of others. This creates an auto-associative network, where partial inputs give rise to complete outputs.
Knocking out CA3 specific NMDA receptors reduces morris water maze performance when mice are trained with full cues, then only presented with partial cues. This prevents LTP from occuring in CA3, destroying long term storage of patterns. The reduced activity in CA3 reduces output to CA1 and the memory cannot be retrieved.
How does the CA3/CA1 network show pattern completion and pattern seperation?
Over time, the same corner of a square shaped box and a circle shaped box will no longer activate the same set of place cells - instead they become different place fields represented by distinct neuronal populations.
Once this training occurs, if the rat is placed in a series of intermediate shaped box (changing slowly from square to circle), there will be a sudden switch between activation of all square place cells firing and all circular place cell firing. There is no intermediate cellular response. This suggests an auto-associative network, which when given resonably similar cues can perform pattern completion and can also perform pattern separation when cues reach a threshold of dissimilarity.
How can a memory engram be studied and manipulated?
Optogenetic manipulations
Through genetic manipulation, animals can be transformed to express channel rhodopsin-2 underneath the c-fos promoter. c-fos is an immediate early gene expressed in a subset of dentate gyral cells when an animal is exposed to a novel environment. Cells which are activated in a new environment therefore express chR2 and can be selectively depolarised.
For example, if a mouse is exposed to a new cage and shocked, shining a light on that engram will reactivate freezing response. Interestingly, this memory engram is maintained even if consolidation mechanisms are blocked.
How are place cell memories encoded and stored?
Like other memories, encoding of place memories does not require long term LTP. Place cell fields are formed even under anisomyocin or NMDA blockade. However, these place fields will not be retained - placing the mouse back in the trained environment will result in completely different subsets of pyramidal cells being activated. The stability of place fields is therefore dependent on long term LTP.
