Background: The lateral habenula (LHb) is a brain structure which is knownto be pathologically hyperactive in depression, thus providing enhancedinhibitory input to the brains’ reward circuitry. As such, inhibition of the LHbhas an antidepressant effect, via disinhibition of the reward circuitry. However,the neural circuity which mediates inhibitory signalling within the LHb remainsto be fully described. Hence, the overarching aim of this project was to studyinhibitory signalling within the LHb, by studying the circuitry formed by neuronsexpressing one of three transgenic markers classically considered to beassociated with inhibitory neurons: Neuron-derived neurotrophic factor (Ndnf),parvalbumin (PV) and somatostatin (SOM).Methods: Circuitry was studied in vitro using patch-clamp electrophysiologyin combination with optogenetic manipulations of neurons expressing theabove molecular markers. Additionally, immunohistochemistry and confocalmicroscopy were used to assess the fraction of neurons expressing thesemarkers 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 dorsalthalamic nucleus; and from SOM-positive neurons in the ventral pallidum.Additionally, we find that within the LHb, these markers are not confined toexclusively inhibitory populations. Rather, we identify physiologically distinct.
| Date of Award | 3 Feb 2020 |
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| Original language | English |
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| Awarding Institution | - University Of Strathclyde
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| Sponsors | EPSRC (Engineering and Physical Sciences Research Council) |
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| Supervisor | Christian Wozny (Supervisor) & Shuzo Sakata (Supervisor) |
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