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Lateral hypothalamic circuits for feeding and reward

Abstract

In experiments conducted over 60 years ago, the lateral hypothalamic area (LHA) was identified as a critical neuroanatomical substrate for motivated behavior. Electrical stimulation of the LHA induces voracious feeding even in well-fed animals. In the absence of food, animals will work tirelessly, often lever-pressing thousands of times per hour, for electrical stimulation at the same site that provokes feeding, drinking and other species-typical motivated behaviors. Here we review the classic findings from electrical stimulation studies and integrate them with more recent work that has used contemporary circuit-based approaches to study the LHA. We identify specific anatomically and molecularly defined LHA elements that integrate diverse information arising from cortical, extended amygdala and basal forebrain networks to ultimately generate a highly specified and invigorated behavioral state conveyed via LHA projections to downstream reward and feeding-specific circuits.

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Figure 1: Electrical stimulation of the LHA produces reinforcement.
Figure 2: The LHA contains a mixture of inhibitory and excitatory neurons.
Figure 3: Vgat-targeted neurons are distinct from MCH- and Orx-producing LHA neurons.
Figure 4: Proposed neurocircuit-wiring diagram based on optogenetic studies.

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Acknowledgements

We thank J. Jennings for input on the manuscript and members of the Stuber laboratory for helpful discussion. This work was supported by the Klarman Family Foundation, the Brain and Behavior Research Foundation, the Foundation for Prader-Willi Research, the Foundation of Hope, the National Institute on Drug Abuse (DA032750 and DA038168), and the Department of Psychiatry at UNC Chapel Hill (G.D.S.). R.A.W. was supported by the Intramural Research Program at the National Institute on Drug Abuse.

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Stuber, G., Wise, R. Lateral hypothalamic circuits for feeding and reward. Nat Neurosci 19, 198–205 (2016). https://doi.org/10.1038/nn.4220

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