Year: 2020
Type: dissertation
Abstract: The habenulopeduncular pathway is known to modulate aversion behaviours, which are tightly associated with Chrna5 gene expression. Chrna5 encodes the α5 nicotinic receptor subunit, which is highly expressed in the interpeduncular nucleus but remains pharmacologically intractable. Here we investigate the impact of this subunit using wild-type and Chrna5-deleted mice. We optogenetically activated the habenulopeduncular pathway; thought to co-release acetylcholine and glutamate, to probe the electrophysiological role of α5 in interpeduncular neurons in acute brain slice. Optogenetic stimulation of this pathway yielded heterogenous responses in wild-type and Chrna5 deleted mice. Unexpectedly, the absence of the Chrna5 gene led to stronger light-evoked glutamatergic and GABAergic neurotransmission. These light-evoked glutamatergic responses were acutely attenuated by nicotinic antagonists in Chrna5 deleted mice. Intriguingly, our optogenetic experiments did not evoke a distinct cholinergic current in either genotype. This work provides insight into the action of Chrna5 on habenulopeduncular circuitry and raises new mechanistic questions.
Source: TSpace (University of Toronto)
Author: Sanghavy Sivakumaran
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3152752568