Visualizing Hypothalamic Network Dynamics for Appetitive and Consummatory Behaviors

• Published in: Cell Vol. 160; no. 3; pp. 516 - 527
• Main Authors: Jennings, Joshua H., Ung, Randall L., Resendez, Shanna L., Stamatakis, Alice M., Taylor, Johnathon G., Huang, Jonathan, Veleta, Katie, Kantak, Pranish A., Aita, Megumi, Shilling-Scrivo, Kelson, Ramakrishnan, Charu, Deisseroth, Karl, Otte, Stephani, Stuber, Garret D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.01.2015
• Subjects: Animals; Appetitive Behavior; Consummatory Behavior; gamma-Aminobutyric Acid - metabolism; Hypothalamic Hormones - metabolism; Hypothalamus - physiology; Intracellular Signaling Peptides and Proteins - metabolism; Melanins - metabolism; Mice; Motivation; Neurons - metabolism; Neuropeptides - metabolism; Orexins; Pituitary Hormones - metabolism; Vesicular Inhibitory Amino Acid Transport Proteins - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2014.12.026

Optimally orchestrating complex behavioral states, such as the pursuit and consumption of food, is critical for an organism’s survival. The lateral hypothalamus (LH) is a neuroanatomical region essential for appetitive and consummatory behaviors, but whether individual neurons within the LH differentially contribute to these interconnected processes is unknown. Here, we show that selective optogenetic stimulation of a molecularly defined subset of LH GABAergic (Vgat-expressing) neurons enhances both appetitive and consummatory behaviors, whereas genetic ablation of these neurons reduced these phenotypes. Furthermore, this targeted LH subpopulation is distinct from cells containing the feeding-related neuropeptides, melanin-concentrating hormone (MCH), and orexin (Orx). Employing in vivo calcium imaging in freely behaving mice to record activity dynamics from hundreds of cells, we identified individual LH GABAergic neurons that preferentially encode aspects of either appetitive or consummatory behaviors, but rarely both. These tightly regulated, yet highly intertwined, behavioral processes are thus dissociable at the cellular level. [Display omitted] •Activation of LH GABAergic neurons produces appetitive and consummatory behaviors•Ablation of LH GABAergic cells attenuates weight gain, consumption, and motivation•LH GABAergic neuronal subsets are molecularly distinct from MCH and Orx cells•In vivo Ca2+ imaging reveals separate appetitive and consummatory encoding networks Deep brain calcium imaging in freely behaving mice reveals that appetitive and consummatory behaviors are encoded in distinct neurons in the hypothalamus, suggesting the existence of separate networks regulating motivation to eat and food consumption.