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On the origin of theta oscillations in the hippocampus

Supervisors: Ole Paulsen, Audrey Hay

Theta oscillations (8-12 Hz) are one of the most striking features of hippocampal activity [1]. These oscillations occur during active wake and REM sleep and have been hypothesised to sustain learning and memory by synchronising neuronal assemblies in the hippocampus. However, how the hippocampal network generates and sustains these oscillations is still not known. It has been suggested that the medial septum (MS), which is necessary for theta oscillations to emerge, entrains theta oscillations in the hippocampus. Indeed, it has been shown that the MS sends cholinergic (excitatory) and GABAergic (inhibitory) projections to the hippocampus. There is good evidence that cholinergic input depolarises pyramidal neurons and that GABAergic interneurons are instrumental for their synchronization [2]. Thus assuming that theta oscillations is generated during the sustained depolarisation of pyramidal dendrites, we hypothesise that the simultaneous depolarisation of pyramidal cells by cholinergic inputs and rhythmic inhibition of hippocampal GABAergic neurons by MS GABAergic inputs are sufficient to generate hippocampal theta rhythm.
To test this hypothesis, we will combine optogenetics, electrophysiology and pharmacology in transgenic mice. We will use optogenetics to activate MS GABAergic neurons at theta rhythm during a cholinergically activated network state. By doing so, we will record, using field recording, the emergence of theta rhythm in the pyramidal layer of the hippocampus and investigate the functional implications for hippocampal memory function [3].

Relevant references

[1] Buzsaki G (2002) Theta oscillations in the hippocampus. Neuron 33: 325-340.

[2] Mann EO, Paulsen O (2007) Role of GABAergic inhibition in hippocampal network oscillations. Trends Neurosci 30: 343-349.

[3] Brzosko Z, Zannone S, Schultz W, Clopath C, Paulsen O (2017) Sequential neuromodulation of Hebbian plasticity offers mechanism for effective reward-based navigation. Elife 6:e27756.