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Title: Diverse firing patterns of neurons of the medial septum and their hippocampal targets
Author: Crump, Michael G.
ISNI:       0000 0004 6060 8448
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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The medial septum has a profound influence on the activity of the hippocampus, through cholinergic and GABAergic innervation. During exploration and paradoxical sleep, the hippocampus produces a prominent voltage oscillation of theta frequency (4-12 Hz), which represents the synchronous activity of hippocampal neurons. This organisation includes the temporal redistribution of inhibition throughout the subcellular domains of pyramidal neurons, via the theta phase locked activity of diverse interneuron populations. GABAergic septo-hippocampal neurons fire rhythmic, phase locked action potentials during theta oscillatory epochs. Within the hippocampus they project exclusively to interneurons; stimulation of the septum disinhibits pyramidal neurons. If the septo-hippocampal projection is inactivated, theta oscillation no longer occurs and animals demonstrate behavioural deficits in episodic memory. This evidence led to the hypothesis that septal rhythmic inhibition of interneurons is a crucial step in the pacing of the hippocampal theta oscillation in vivo. I used extracellular recording and the juxtacellular labelling method of neurons under anaesthesia in vivo to investigate how the electrophysiological activity of septal neurons correlated with the identity of the cell, its axonal arbour and synaptic targets in the hippocampus. I tested the hypothesis that septal neurons display a selective and non-uniform innervation of interneurons and the firing phase and/or spike timing of septal neurons is correlated with that predicted of the innervated hippocampal interneuron(s). I found a diversity of medial septal neurons, which was partially predicted by the firing frequency change during sharp wave associated ripple oscillations. Septal neurons which display significantly different firing patterns and axonal arbours may share molecular markers detected by immunohistochemistry. The axonal arbours of septal neurons were limited to a relatively small area within the hippocampus. Within those regions I defined some of the synaptic targets of three neurons and suggest that septal GABAergic neurons selectively innervate hippocampal interneuron types. Furthermore, the preferred theta phase of septal neurons was out of phase with that predicted for their identified target cells, indicating that septal GABAergic neurons may suppress the firing of interneurons rhythmically during theta.
Supervisor: Somogyi, Peter ; Lapray, Damien ; Viney, Tim Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available