Author: Carus-Cadavieco M1, Gorbati M1, Ye L2,3, Bender F1, van der Veldt S1, Kosse C4, Börgers C5, Lee SY2, Ramakrishnan C2, Hu Y1, Denisova N1, Ramm F1, Volitaki E1, Burdakov D4, Deisseroth K2,3,6, Ponomarenko A1, Korotkova T1
1Behavioural Neurodynamics Group, Leibniz Institute for Molecular Pharmacology (FMP)/ NeuroCure Cluster of Excellence, Berlin, Germany.
2Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
3Howard Hughes Medical Institute; Stanford University, Stanford, California 94305, USA.
4The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
5Department of Mathematics, Tufts University, Medford, Massachusetts 02155, USA.
6Department of Psychiatry and Behavioural Sciences, W080 Clark Center, 318 Campus Drive West, Stanford University, Stanford, California 94305, USA.
Date published: 2017 Feb 1
Other: Special Notes: doi: 10.1038/nature21066. [Epub ahead of print] , Word Count: 244
Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to-treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus, the activity of which also changes in anticipation of feeding onset. The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks, but cognitive regulation of feeding-related behaviours is not yet understood. Cortical cognitive processing involves gamma oscillations, which support memory, attention, cognitive flexibility and sensory responses. These functions contribute crucially to feeding behaviour by unknown neural mechanisms. Here we show that coordinated gamma (30-90 Hz) oscillations in the lateral hypothalamus and upstream brain regions organize food-seeking behaviour in mice. Gamma-rhythmic input to the lateral hypothalamus from somatostatin-positive lateral septum cells evokes food approach without affecting food intake. Inhibitory inputs from the lateral septum enable separate signalling by lateral hypothalamus neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. Upstream, medial prefrontal cortical projections provide gamma-rhythmic inputs to the lateral septum; these inputs are causally associated with improved performance in a food-rewarded learning task. Overall, our work identifies a top-down pathway that uses gamma synchronization to guide the activity of subcortical networks and to regulate feeding behaviour by dynamic reorganization of functional cell groups in the hypothalamus.
PMID: 28146472 DOI: 10.1038/nature21066