Optogenetic Activation of AgRP Neurons Lengthens and Deepens Daily Torpor in the Mouse

In response to food scarcity and low ambient temperatures, mice enter bouts of torpor resulting in energy conservation. During a torpor bout, mice exhibit a substantial decrease in body temperature (T b ), heart rate (HR), and metabolic rate. The neurobiology of torpor is largely unknown. It has been shown that peripheral administration of ghrelin, a stomach‐derived hormone released during energy deprivation, to calorically restricted mice deepens and lengthens torpor bouts. It is thought that ghrelin induces its physiological effects by activating Agouti‐related protein (AgRP) containing neurons in the arcuate nucleus of the hypothalamus. Therefore, we hypothesized that direct stimulation of AgRP neurons would decrease the minimum T b of torpid mice and increase the time spent in torpor. To test this hypothesis, mice were implanted with ECG/T b telemeters and hypothalamic AgRP neurons were selectively targeted with the light‐sensitive channelrhodopsin‐2 transgene. Mice were calorically restricted daily (65% of normal caloric intake) until regular daily torpor bouts were achieved. On baseline days, when AgRP neurons were not activated, minimum T b was 25.6 ± 0.8 °C and time in torpor was 233 ± 34 minutes. When AgRP neurons were stimulated for one hour during entry into torpor (20 Hz for 1 second every 4 seconds for 60 minutes), minimum T b was significantly lower (22.8 ± 0.3 °C) and torpor bouts were significantly longer (435 ± 29 min). These data support the hypothesis that AgRP neurons directly regulate torpor physiology and begin to elucidate the neural circuits responsible for torpor regulation. Support or Funding Information Supported by 1R15HL120072‐01A1 to SJS and by 1R15DK105510 to MC