Identifying mechanisms enabling deep diving and safe emergence from torpor

Torpor is a remarkable protective state characterized by hypothermia/hypometabolism followed by a dramatic rewarming phase. Its neuronal circuits and cellular mechanisms are largely undiscovered. I will address how the brain drives entry and exit from torpor through three workstreams. (1) Identify whether the preoptic area to dorsomedial hypothalamus projection triggers torpor. I will target the pathway using retrograde vectors and chemogenetics to assess necessity and sufficiency for torpor induction. This will be extended using activity-dependent genetic TRAPing to identify neurons engaged during torpor. These behavioural experiments, conducted in torpid (mice) and non-torpid (rats) species, will be complemented by cellular and synaptic analysis of the projection neurons. (2) Characterize the neural mechanisms of torpor emergence. The exit from torpor is rapid and without deleterious consequences. I will use TRAPing to identify candidate mediating regions and then causally test whether distinct sets of neurons regulate induction/emergence using optogenetic circuit manipulation. (3) Determine how neuronal networks are engaged to trigger torpor. I will test whether tanycytes act as the intermediary between peripheral cues and central regulation of torpor. This will be achieved using confocal/electron microscopy and optogenetic manipulations to measure cellular and synaptic excitability changes at points through the torpor-arousal cycle.