Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C087

Oral Communications

Neuronal coding of food-seeking and food intake in hypothalamic networks

M. Carus-Cadavieco1,2, M. Gorbati2, L. Ye3, F. Bender2, S. Van der Veldt2, K. Deisseroth3, A. Ponomarenko4,2, T. Korotkova1,2

1. Research group "Neuronal Circuits and Behavior", Max Planck Institute for Metabolism Research, Cologne, Germany. 2. Junior Group "Behavioral Neurodynamics", FMP Leibniz Institute/ NeuroCure Cluster of Excellence, Berlin, Germany. 3. Stanford University, Stanford, California, United States. 4. Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, Dusseldorf, Germany.

Feeding is largely regulated by hypothalamic neuronal circuits, yet little is known about neuronal coding of different feeding-related behaviours by the lateral hypothalamus (LH) and its extrahypothalamic inputs. Combining optogenetics with electrophysiological recordings in freely behaving mice, we have identified a novel top-down pathway from medial prefrontal cortex via lateral septum to lateral hypothalamus, which utilizes gamma synchronization (30-90 Hz) to regulate food-seeking by dynamic reorganization of functional cell groups in the LH (1). During viral injections and electrode implantations mice were anaesthetized using carprofen (s.c., 5 mg/kg), lidocain (local) and isoflurane (inhalation, 1.5-3% in oxygen). All animal experimental procedures accorded with current national legislation/guidelines. The gamma-rhythmic input enabled fine-time scale separation of LH cells according to their feeding-related activity: a subset of LH neurons, active at the food location ("food-match" cells), prominently reduced their firing during the gamma oscillation trough. In contrast, LH cells, which were preferentially active distantly from the food zone ("food-mismatch" cells), showed high excitability at the gamma trough. The selective induction of food seeking (reduced latency: control: n = 8 mice, opsin: n = 10 mice; P = 0.0004, t-test; preference of the food zone: control: n = 8 mice, opsin: n = 12 mice, P = 0.0047, binomial test), without changes in food intake (control: n = 8 mice, opsin: n = 9 mice, P = 0.8, t-test) by gamma-rhythmic stimulation contrasts with an increased food intake during somatic optogenetic stimulation of LH GABA (Vgat-positive) cells (optogenetic stimulation (control: n = 7 mice, opsin: n = 5 mice, P = 0.0078), a subgroup of LH cells, which also mediates arousal (2). To investigate intrahypothalamic network responses which underlie differential functions of LH Vgat cells vs. lateral septum-LH projections in feeding behaviours, we studied effects of these manipulations on firing of LH neurons. Optogenetic stimulation of LH Vgat cells evoked a prominent increase in firing of "food-match" but not "food-mismatch" cells (mismatch: n = 31 cells, match: n = 15 cells; P = 0.007, t-test). In contrast, gamma-frequency optogenetic stimulation of LS-LH projections increased firing of "food-mismatch" rather than "food-match" neurons (mismatch: n = 12 cells, match: n = 20 cells; P = 0.019, Mann-Whitney test). Thus, neuronal populations in the lateral hypothalamus, as well as top-down gamma-rhythmic signaling, differentially code food-seeking and food intake.

Where applicable, experiments conform with Society ethical requirements