Hypothalamic Cell Types and Circuits that Drive Survival Behaviors

Seminar | December 3 | 2-3 p.m. | 125 Li Ka Shing Center

 Yeka Aponte, National Institute on Drug Abuse, NIH

 Neuroscience Institute, Helen Wills

The diverse collection of genetically-distinct cell types in the lateral hypothalamus (LH) is crucial for orchestrating a variety of motivated behaviors that facilitate survival. A pivotal role of the LH in regulating appetitive and reward-related behaviors has been evident for decades. However, the contributions of LH circuits to other survival behaviors has been less explored. Here we examine how two lateral hypothalamic neuron populations identified by the expression of the calcium-binding protein parvalbumin (PVALB; LHPV) or leptin receptor (LHLEPR), modulate nociception and motivation in mice, respectively. We find that photostimulation of LHPV neurons suppresses nociception to an acute, noxious thermal stimulus, whereas LHLEPR neuronal activation promotes motivation for food and water reward. Moreover, we demonstrate that LHPV axons form functional excitatory synapses on neurons in the ventrolateral periaqueductal gray (vlPAG), and photostimulation of these axons mediates antinociception to both thermal and chemical stimuli. Furthermore, we mapped LHLEPR axonal projections and demonstrated that they target the ventral tegmental area (VTA), form functional inhibitory synapses with non-dopaminergic VTA neurons, and their activation promotes motivation for food reward. Together, these results directly implicate LHPV neurons in modulating nociception and identify LHLEPR neurons as modulators within a hypothalamic-ventral tegmental circuit that gates motivation, thus expanding the repertoire of survival behaviors regulated by LH circuits.