Sensory perception drives food avoidance through excitatory basal forebrain circuits

Abstract

Appetite is driven by nutritional state, environmental cues, mood, and reward pathways. Environmental cues strongly influence feeding behavior, as they can dramatically induce or diminish the drive to consume food despite homeostatic state. Here, we have uncovered an excitatory neuronal population in the basal forebrain that is activated by food-odor related stimuli, and potently drives hypophagia. Notably, we found that the basal forebrain directly integrates environmental sensory cues to govern feeding behavior, and that basal forebrain signaling, mediated through projections to the lateral hypothalamus, promotes selective avoidance of food and food-related stimuli. Together, these findings reveal a novel role for the excitatory basal forebrain in regulating appetite suppression through food avoidance mechanisms, highlighting a key function for this structure as a potent integrator of sensory information towards governing consummatory behaviors.

Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior

“…The avoidance response we observed is consistent with a growing body of work implicating BF vGluT2 neurons in the response to aversive stimuli and in constraining reward seeking (Faget et al, 2016;Tooley et al, 2018;Patel et al, 2019). Surprisingly, in our experiments this avoidance response was not maintained one day later.…”

“…The different responses in cholinergic and PV neurons also suggest that the effect of stimulating BF vGluT2 neurons is not mediated by the local connections within BF. Instead, our anterograde tracing results presented here together with prior literature suggest that the avoidance response elicited by optogenetic stimulation of BF vGluT2 neurons is most likely mediated by a coordinated activation of neurons in the lateral habenula, lateral hypothalamus and VTA (Knowland et al, 2017;Tooley et al, 2018;Laziridis et al, 2019;Patel et al, 2019;Barbano et al, 2020).…”

“…Thus, BF vGluT2 neurons are involved in immediate avoidance responses but one 30 min session of optogenetic stimulation was not sufficient to develop a learned avoidance response. The signals which activate BF vGluT2 neurons to cause avoidance behavior are not fully understood but an interesting recent study identified an excitatory population of BF neurons that are activated by food odor-related stimuli and drive selective avoidance of food with unpleasant odors, in part via projections to the lateral hypothalamus (Patel et al, 2019).…”

Paraventricular hypothalamus mediates diurnal rhythm of metabolism

“…To verify that Kir2.1-induced obesity is caused by defective neuron responsiveness, we next aimed to examine whether clamping PVH neuron activity at higher levels also disrupts neuron responsiveness, reduces diurnal rhythms in metabolism, and promotes obesity. Towards this, we bilaterally delivered conditional AAV vectors encoding a slow inactivation and low-threshold sodium channel from bacteria (NachBach) 31,32 to the PVH of Sim1-Cre mice. In PVH Sim1 neurons, we verified cell type-specific expression of Credependent AAV-EF1a-FLEX-EGFP-P2A-mNachBac ( Fig.…”

Frequency-independent biological signal identification (FIBSI): A free program that simplifies intensive analysis of non-stationary time series data

“…Previously published methods circumvent these issues by different means. For example, 108 some focus on low frequency, high signal-to-noise ratio data collected from ROIs with substantial 109 physical separation from each other [7,8], use post-hoc analyses with a second identification 110 method (e.g., antibody staining or tight localization to neuronal nuclei) to tie ROIs to relevant 111 physical locations [9,10], use a short stimulus and test window to isolate activity [11], and/or use 112 phasic stimulations to identify ROIs and the Fourier transform to reduce noise [12][13][14]. In many 113 systems, however, the choice of ROIs is not flexible, and ROIs containing the relevant biological 114 signal of interest are intrinsically noisy, so the above-mentioned approaches are not applicable.…”