Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice

Abstract

For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.

A Normative Framework Dissociates Need and Motivation in Hypothalamic Neurons

“…Previous studies have not fully accounted for the multitude of dynamic events that can influence the activity of LH LepR neurons ( 39, 50 ). Past fragmented studies demonstrated that LH LepR neurons reinforce lever pressing, possess rewarding properties ( 50 ), and initiation of seeking or consummatory behaviours for food ( 38 ). In our experimental paradigm, LH LepR neural activity increased at accessibility moment and decreased at inaccessibility moment.…”

“…A shelter was placed and an electrical shock was given as punishment in a square chamber, as previously reported ( 38 ). All reward-associated cues (e.g., visual or sound cues) were eliminated to measure voluntary seeking behaviour initiation.…”

“…However, other studies argue that despite the deactivation of AgRP neurons, the residual firing of AgRP neurons directly encodes the food-related motivation responsible initiating behaviours such as searching, foraging, consuming or instrumental responses ( 36, 37 ). We and other researchers have reported that leptin-receptor neurons in the lateral hypothalamus (LH LepR ) are activated during food consumption ( 38, 39 ). Similar to activating AgRP neurons, activation of LH LepR neurons increases eating behaviours ( 38 ).…”

“…We and other researchers have reported that leptin-receptor neurons in the lateral hypothalamus (LH LepR ) are activated during food consumption ( 38, 39 ). Similar to activating AgRP neurons, activation of LH LepR neurons increases eating behaviours ( 38 ). Collectively, the activation of both AgRP neurons and LH LepR hypothalamic neuron populations evokes eating behaviours which complicate the understanding of their roles as either need or motivation for eating.…”

“…Similar to activating AgRP neurons, activation of LH LepR neurons increases eating behaviours (38). Collectively, the activation of both AgRP neurons and LH LepR hypothalamic neuron populations evokes eating behaviours which complicate the understanding of their roles as either need or motivation for eating.…”