The Inhibitory Circuit Architecture of the Lateral Hypothalamus Orchestrates Feeding

Abstract

The growing prevalence of overeating disorders is a key contributor to the worldwide obesity epidemic. Dysfunction of particular neural circuits may trigger deviations from adaptive feeding behaviors. The lateral hypothalamus (LH) is a crucial neural substrate for motivated behavior including feeding, but the precise functional neurocircuitry that controls LH neuronal activity to engage feeding has not been defined. We observed that inhibitory synaptic inputs from the extended amygdala preferentially innervate and suppress the activity of LH glutamatergic neurons to control food intake. These findings help explain how dysregulated activity at a number of unique nodes can result in a cascading failure within a defined brain network to produce maladaptive feeding.

The Human BNST: Functional Role in Anxiety and Addiction

“…For example, the BNST is involved in the anxiogenic effects of cocaine intoxication (Wenzel et al, 2014). In addition, there is compelling evidence that the BNST mediates stressinduced reinstatement of drug-seeking behavior (Buffalari and See, 2011;Erb et al, 2001;Flavin and Winder, 2013;Jennings et al, 2013a), thus serving an important role in understanding relapse following a period of abstinence. Similar to the light-enhanced startle and CRF-enhanced startle described earlier, withdrawal from drugs of abuse also enhances startle response, providing a model for testing effects of pharmacological agents on withdrawal.…”

Embryonic Origin of the Islet1 and Pax6 Neurons of the Chicken Central Extended Amygdala Using Cell Migration Assays and Relation to Different Neuropeptide-Containing Cells

“…In addition, the output of the BSTL to the hypothalamus, although primarily being GABAergic [Jennings et al, 2013a] (this GABAergic projection reaching the lateral hypothalamus is involved in feeding), also includes a minor subset of glutamatergic projections [Csáki et al, 2000]. The glutamatergic neurons of the murine BSTL are different from the ENK-, CRF-and/or NT-containing cells, since 100% of the latter are GABAergic [Day et al, 1999], which is typical of cells that originate in the subpallium [Abellán and Medina, 2009].…”

“…The CeA, the ITC and the BSTL have been shown to be essential for fear and anxiety responses [Phelps and LeDoux, 2005;Paré and Durvarci, 2012]. Moreover, the CeA and BSTL are also involved in emotional control or modulation of ingestion [Petrovich et al, 2009;Jennings et al, 2013a], pain [Fox and Sorenson, 1994;Kang et al, 1998] and reward/aversion [Jennings et al, 2013b]. Such multifaceted functions are controlled or modulated by different neuron subsets of the EAce and their projections.…”

Agouti-Related Protein Neuron Circuits That Regulate Appetite

“…1). Consistent with this, LHA glutamate neuron inhibition evokes feeding [28]. However, the precise relationship to AGRP neuron projections is not yet clear.…”

“…Nevertheless, anatomical analyses have shown substantial interconnectivity between these brain areas, indicating a network across which feeding may be coordinated. For example, optogenetic activation of GABA-releasing BNST neurons (BNST GABA ) elicits voracious eating [28]. Using optogenetic circuit mapping in conjunction with single-cell RT-PCR, this was found to involve an inhibitory synaptic projection to the LHA that selectively targets glutamate neurons (fig.…”