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Towards a Systematic Understanding of the Neural Circuits of the Periaqueductal Grey (PAG)

Tsang, Fai

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Abstract

The midbrain periaqueductal grey (PAG) is commonly recognised as the exit relay for the coordination and execution of a wide range of instinctive behaviours, such as defense, reproduction and predation. In line with its functional diversity, are the range of inputs it receives from higher cortical and subcortical areas as well as ascending spinal pathways, and the various neurotransmitter and neuromodulatory mechanisms active in its different subregions. However, the lack of a comprehensive cell-type classification of the PAG hinders systematic investigations into the intricacies of its many behavioural roles. Here, we applied high-throughput single neuronal nucleus RNA-sequencing to profile transcriptomes of adult mouse PAG neurons. Our data revealed at least 9 distinct PAG neuronal subpopulations, marked by differential expressions of neurotransmitter, neuromodulator and ion channel genes. In addition, using a combination of optogenetic manipulations and a carefully designed defense test battery, we identified separate functions of dPAG vGlut2+, PACAP+ and Tac2+ neurons in triggering and modulating defensive behaviour. We showed that dlPAG vGlut2+ neurons project to the Cuneiform nucleus, and this projection is an output pathway for PAG elicited escape behaviour. Our work supports the existence of molecularly distinct, functionally divergent pathways in the PAG underlying defensive behaviour, and demonstrates a framework towards a systematic dissection of cell-type specific functions of complex brain regions.

Item Type: Dissertation
Supervisor: Noh, Dr. Kyung-Min
Date of thesis defense: 5 December 2018
Date Deposited: 11 Dec 2018 14:11
Date: 2018
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
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