Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour

Abstract

Categorically distinct basic drives (for example, for social versus feeding behaviour1–3) can exert potent influences on each other; such interactions are likely to have important adaptive consequences (such as appropriate regulation of feeding in the context of social hierarchies) and can become maladaptive (such as in clinical settings involving anorexia). It is known that neural systems regulating natural and adaptive caloric intake, and those regulating social behaviours, involve related circuitry4–7, but the causal circuit mechanisms of these drive adjudications are not clear. Here we investigate the causal role in behaviour of cellular-resolution experience-specific neuronal populations in the orbitofrontal cortex, a major reward-processing hub that contains diverse activity-specific neuronal populations that respond differentially to various aspects of caloric intake8–13 and social stimuli14,15. We coupled genetically encoded activity imaging with the development and application of methods for optogenetic control of multiple individually defined cells, to both optically monitor and manipulate the activity of many orbitofrontal cortex neurons at the single-cell level in real time during rewarding experiences (caloric consumption and social interaction). We identified distinct populations within the orbitofrontal cortex that selectively responded to either caloric rewards or social stimuli, and found that activity of individually specified naturally feeding-responsive neurons was causally linked to increased feeding behaviour; this effect was selective as, by contrast, single-cell resolution activation of naturally social-responsive neurons inhibited feeding, and activation of neurons responsive to neither feeding nor social stimuli did not alter feeding behaviour. These results reveal the presence of potent cellular-level subnetworks within the orbitofrontal cortex that can be precisely engaged to bidirectionally control feeding behaviours subject to, for example, social influences.

Targeted photostimulation uncovers circuit motifs supporting short-term memory

“…8, p < 0.001 Kolmogorov-Smirnov test; Methods). These behavioral changes are consistent with other studies that have manipulated small numbers of neurons during behavior 20–22 .…”

Dopamine neuron ensembles signal the content of sensory prediction errors

“…One possibility is that information about the content to be learned might be contained, at least partly, in the pattern of firing across an ensemble of dopamine neurons. It is now widely accepted that information is represented in areas like cortex and hippocampus not by individual neurons, but rather in a distributed fashion in the firing of groups of cells (Gochin et al, 1994;Jennings et al, 2019;Jones et al, 2007;Rich and Wallis, 2016;Rigotti et al, 2013;Schoenbaum and Eichenbaum, 1995;Wikenheiser and Redish, 2015;Wilson and McNaughton, 1993). If this is true for the cortex and hippocampus, then why not for the midbrain dopamine system?…”

Value-guided remapping of sensory circuits by lateral orbitofrontal cortex in reversal learning

“…To directly probe neuronal activity in lateral OFC and S1 during learning and reversal learning, we performed in vivo two-photon Ca 2+ imaging in transgenic mice expressing GCaMP6f in superficial excitatory layer (L)2/3 neurons. We targeted lateral OFC, which resides deep in the frontal cortex 13,14 , by imaging via a gradientindex lens that was inserted through a chronically implanted cannula ( Fig. 2a; Supplementary Fig.…”