Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking

Abstract

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.

The form and function of channelrhodopsin

“…4B). These high-speed variants are often used when precise control and temporal stationarity is desired, particularly in fast-spiking cells [involved in sleep, fear, and feeding (46–49)]. Further engineered or naturally occurring ChRs were later identified that also exhibited fast deactivation and/or improved temporal stationarity [e.g., ChIEF, Chronos, and other variants; reviewed here (14, 41, 42, 50, 51)], and the fast-ChR toolkit grew further as ChETA and ChIEF modifications proved portable to other ChRs, including designer variants with larger photocurrents (51) and redshifted spectra (discussed below).…”

Hunger and Satiety Gauge Reward Sensitivity

“…Interestingly, the reciprocal VTA-LH projection is observed to be activated in response to reward omission; the disorganized feeding behavior from LH-VTA projection may occur because of the lack of this feedback information (62). Indeed, a recent study evaluating lateral septum inhibitory influence on the LH found that one subset of LH GABAergic neurons are activated during food approach and another during food consumption, indicating that a temporal sequence of GABAergic subpopulation activation occurs to produce successful food consumption (63). …”

The role of corticostriatal–hypothalamic neural circuits in feeding behaviour: implications for obesity

“…; Carus‐Cadavieco et al . ). Specifically, inhibitory inputs to LH neurons can drive self‐stimulation and feeding in well‐fed mice (Jennings et al .…”

“…A recent study by Carus‐Cadavieco et al . () identified a top‐down pathway connecting the medial prefrontal cortex, lateral septum (LS) and LH that uses coordinated gamma oscillations to organize feeding behaviour (Carus‐Cadavieco et al . ).…”

“…() identified a top‐down pathway connecting the medial prefrontal cortex, lateral septum (LS) and LH that uses coordinated gamma oscillations to organize feeding behaviour (Carus‐Cadavieco et al . ). By examining the activity of LH neurons in vivo , the authors demonstrated that there are two subpopulations of LH Vgat neurons that respond when a mouse is either close to food, or at a distance, both of which are separately activated during gamma oscillations within the LH (Carus‐Cadavieco et al .…”