Neural circuit mechanism underlying the feeding controlled by insula-central amygdala pathway

Abstract

<jats:title>Summary</jats:title><jats:p>Central nucleus of amygdala (CeA) contains distinct populations of neurons that play opposing roles in feeding. The circuit mechanism of how CeA neurons process information sent from their upstream inputs to regulate feeding is still unclear. Here we show that activation of the neural pathway projecting from insular cortex neurons to CeA suppresses food intake. Surprisingly, we find that the inputs from insular cortex form excitatory connections with similar strength to all types of CeA neurons. To reconcile this puzzling result, and previous findings, we developed a conductance-based dynamical systems model for the CeA neuronal network. Computer simulations showed that both the intrinsic electrophysiological properties of individual CeA neurons and the overall synaptic organization of the CeA circuit play a functionally significant role in shaping the CeA neural dynamics. We successfully identified a specific CeA circuit structure that reproduces the desired circuit output consistent with existing experimentally observed feeding behaviors.</jats:p>

Distinct circuits in rat central amygdala for defensive behaviors evoked by socially signaled imminent versus remote danger

“…56 In mice, the IC-CeA pathway seems to be involved in carrying information about the aversive emotional state, inducing such behaviors as feeding suppression, place avoidance, and reducing exploration. 44,57,58 Our observation that inhibition of the AI-CeA pathway increased rearing is generally consistent with the literature. 58 What remains to be explained is why this projection seems to be preferentially recruited during the remote threat paradigm, which is otherwise characterized by active behavior (particularly rearing).…”

“…This observation is consistent with previous reports suggesting that the same CeA circuits can modulate intensity of different ongoing behaviors, depending on the current environmental context. 20,43,44 Because expression of the c-fos-dependent constructs used in this study can be evoked by any novelty in the environment, to control for their non-specific expression, i.e., unrelated to interaction with the demonstrators, we tested animals injected with the same constructs and exposed to similar conditions as the experimental groups except for the interaction with emotionally aroused partners. 26,45 Further, our preliminary data showed that expression of the constructs used here takes at least 2 h, and thus our optogenetic manipulations in the exploration and social interaction tests should not have led to stimulation of non-specific circuits.…”

“…58 Second, projections from the IC target both PKC-dpositive and -negative CeA cells, depolarizing them to a similar extent. 44 This finding seems puzzling, as the two populations are known to have opposite effects on feeding 23 and exploration. 22 The remote threat paradigm recruited almost exclusively the PKC-d-negative cells, whereas the chemogenetic manipulation allowed us only to non-specifically inhibit all the AI-CeA projections.…”

“…59 Taken together, the data suggest that the projection from the IC to the CeA signals a typically negative emotional state. What will be the exact behavioral response to this signal seems to be further determined at the level of the within-CeA neuronal activation 44 and might be influenced by the animal's state, 57 type of stimulus, 59 or previous experience. 60 To sum up, the CeA projections from the BLA and AI regulate exploration.…”

Overview of the central amygdala role in feeding behaviour

“…The conductance-based model with a dynamical system for the CeA neural network represents the biophysical interpretation of an excitable cell in regulating the feeding behaviour 75 . The intra-connections and projections modulate feeding behaviour in the CeA 36 where there are direct and indirect connections with different hypothalamic nuclei 52; 53; 76 .…”