Optogenetic investigation of the neuronal ensembles encoding learned behaviour.
Doctoral thesis, UCL (University College London).
Neuronal circuits in the mammalian brain are capable of receiving and storing inputs from the external world. Over the last century, theoretical predictions and experimental evidence have converged to indicate that sparse populations of neurons are responsible for encoding stimuli or behaviours. Prominent theories, most notably those of D. Hebb, have also indicated how information could then be recalled from these populations, or ‘assemblies’, of neurons. In particular, re-activation of just part of an assembly would selectively activate the rest of it and ultimately lead to recall of the stored stimulus or behaviour. However, no direct experimental evidence exists to prove (or disprove) this hypothesis. In this thesis I present work aimed at directly addressing this issue, focusing on neuronal circuits in the mouse hippocampus. I first devised a technique to allow selective stimulation of functionally defined populations of neurons. By using the mouse c-fos promoter I was able to limit expression of the optogenetic probe Channelrhodopsin-2 to hippocampal neurons involved in the learning phase of a fear-conditioning task. I then tested whether re-activation of a subset of these functionally defined cells would lead to recall of the associated freezing behaviour. I found that when the relevant assembly is stimulated, activation of a few cells is sufficient to cause recall of the learned behaviour. On the contrary, activation of a randomly selected population of neurons did not lead to behavioural recall. The behaviour observed replicated the hallmarks of classic fear conditioning and was subject to extinction upon repeated light stimulation. Finally, I attempted to develop a strategy to perform similar experiments in the neocortex, where other circuits crucial to behaviour exist. Altogether, these results provide direct experimental evidence regarding the function of neuronal assemblies and their role in the generation of a behavioural output.
|Title:||Optogenetic investigation of the neuronal ensembles encoding learned behaviour|
|Additional information:||Permission for digitisation not received|
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