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Title: Behaviour-dependent activity and synaptic organisation of septo-hippocampal GABAergic neurons
Author: Joshi, Abhilasha
ISNI:       0000 0004 6500 7553
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Animal behaviour is coordinated by biological rhythms over multiple timescales. In the temporal cortex, rhythmic oscillatory activity in the 5 to 12 Hz theta frequency range supports behaviour through temporal windows of changes in excitability and circuit computation. Subcortical inputs, including those from the medial septum are thought to generate the theta oscillatory activity. However, the rules of innervation of identified types of cortical cells in different cortical regions by a diverse population of septal neurons are largely unknown. During my DPhil studies, I tested the hypothesis that medial septal GABAergic neurons which exhibit distinct activity patterns would express distinct molecular marker combinations and have distinct synaptic partners. In Chapters 1 and 2, I formulate my research questions and explain the methodology used. My main findings are presented in chapters 3 to 7. In Chapter 3, I present the strategy used to identify four populations of rhythmic medial septal neurons based on their spike-train dynamics in the mouse in vivo. In Chapter 4, I present a detailed analysis of the spike-timing and molecular parameters of a specialised population of rhythmic neuron, the Teevra cells. Teevra cells are PV+, do not change their firing rate from rest to running and fire short bursts of action potentials preferentially at the trough of both CA1 theta and slow irregular activity recorded in stratum pyramidale. In Chapter 5, I show that Teevra cells selectively innervate axo-axonic cells and CCK-immunopositive interneurons in hippocampal area CA3, bypassing CA1, CA2, and the dentate gyrus. In Chapter 6, I show that Teevra cell axons terminate in restricted septo-temporal segments of CA3 according to their rhythmicity. Finally, in Chapter 7, I present the Komal cells, which fire long bursts of action potentials at the peak of theta, increase their firing rate during running, and preferentially innervate extrahippocampal cortices. I discuss the broad relevance of my observations in Chapter 8. Overall, my results show an unexpected specialisation in the organisation of medial septal GABAergic inputs to the temporal cortex. Teevra cells fire maximally at the trough and preferentially innervate the CA3 whereas Komal cells fire maximally at the peak and target extrahippocampal cortices, thereby coordinating the timing of converging glutamatergic inputs to CA1 via disinhibition. This cortical-region-specific GABAergic innervation by physiologically distinct septal neuronal types suggests a general mechanism for the coordination of network activity, both during regular theta oscillations and irregular large amplitude waves, providing windows of computation through synchronisation of neuronal activity in the cortex.
Supervisor: Somogyi, Peter ; Dupret, David Sponsor: Medical Research Council ; Felix Scholarship ; Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available