A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding

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<jats:title>Abstract</jats:title><jats:p>Marked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLM<jats:sup>CA</jats:sup>) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLM<jats:sup>CA</jats:sup> neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLM<jats:sup>CA</jats:sup> neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLM<jats:sup>CA</jats:sup> projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLM<jats:sup>CA</jats:sup>–pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLM<jats:sup>CA</jats:sup>–pPVT–NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.</jats:p>

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  • Nature Communications

    Nature Communications 11 (1), S10-, 2020-12-04

    Springer Science and Business Media LLC

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