An investigation of the neural circuitry that mediates inhibitory signalling within the lateral habenula

Student thesis: Doctoral Thesis

Abstract

Background: The lateral habenula (LHb) is a brain structure which is known to be pathologically hyperactive in depression, thus providing enhanced inhibitory input to the brains' reward circuitry. As such, inhibition of the LHb has an antidepressant effect, via disinhibition of the reward circuitry. However, the neural circuity which mediates inhibitory signalling within the LHb remains to be fully described. Hence, the overarching aim of this project was to study inhibitory signalling within the LHb, by studying the circuitry formed by neurons expressing one of three transgenic markers classically considered to be associated with inhibitory neurons: Neuron-derived neurotrophic factor (Ndnf), parvalbumin (PV) and somatostatin (SOM). Methods: Circuitry was studied in vitro using patch-clamp electrophysiology in combination with optogenetic manipulations of neurons expressing the above molecular markers. Additionally, immunohistochemistry and confocal microscopy were used to assess the fraction of neurons expressing these markers which were also GABAergic. Results: This work identifies three sources of inhibitory input to the LHb, arising from both local PV-positive neurons, and those in the medial dorsal thalamic nucleus; and from SOM-positive neurons in the ventral pallidum. Additionally, we find that within the LHb, these markers are not confined to exclusively inhibitory populations. Rather, we identify physiologically distinct.
Date of Award3 Feb 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsEPSRC (Engineering and Physical Sciences Research Council)
SupervisorChristian Wozny (Supervisor) & Shuzo Sakata (Supervisor)

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