A 'cell assembly' is defined as a sparse group of neurons repeatedly activated during a certain mental process. Theoretical and experimental work suggests that the organised activation of cell assemblies underlies cognitive abilities such as memory formation and recall, planning and decision making. The mechanisms leading to the formation, reactivation and disbanding of cell assemblies are still poorly understood. Shedding light on these mechanisms is important for two reasons. First, it could provide crucial information on the neural underpinnings of memory and cognition. Second, it could pave the way to better understand conditions in which cell assembly activity appears altered (in particular neurodevelopmental disorders such as schizophrenia).
Inhibitory neurons releasing the neurotransmitter GABA are believed to be fundamental units controlling cell assembly formation and reactivation. Leading theories posit that inhibitory neurons help maintain sparsity (i.e. making sure that only a few neurons are active in a short time window) and help segregate cell assemblies representing different brain operations. However, direct evidence and detailed mechanisms for this theory are still lacking. The rodent hippocampus represents a valuable framework to investigate the role of inhibition in cell assembly activation for various reasons. First, the hippocampus is required for encoding episodic memories. Second, the sequential activation of hippocampal cell assemblies (which are excitatory pyramidal cells) can encode both spatial and temporal information. Third, the inhibitory circuits of the hippocampus are well understood.
The aim of the present project was to understand how inhibitory (GABAergic) circuits orchestrate the activation of hippocampal cell assemblies. In the first part of the project, we sought to study the relationship between a special inhibitory subtype ('hub neurons', which are born earliest in development) and cell assemblies. Since the physiological properties and connectivity of these cells was unknown, the aim was also to shed light on these aspects. The second part of the project aimed at studying the spatiotemporal dynamics of inhibition in CA1 region of the hippocampus, at examining the relationship of these dynamics with cell assembly activity and at perturbing inhibitory neurons' activity using optogenetics.
