Dataset Information

The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits.

ABSTRACT: SIM1-expressing paraventricular hypothalamus (PVH) neurons are key regulators of energy balance. Within the PVHSIM1 population, melanocortin-4 receptor-expressing (PVHMC4R) neurons are known to regulate satiety and bodyweight, yet they account for only half of PVHSIM1 neuron-mediated regulation. Here we report that PVH prodynorphin-expressing (PVHPDYN) neurons, which notably lack MC4Rs, function independently and additively with PVHMC4R neurons to account for the totality of PVHSIM1 neuron-mediated satiety. Moreover, PVHPDYN neurons are necessary for prevention of obesity in an independent but equipotent manner to PVHMC4R neurons. While PVHPDYN and PVHMC4R neurons both project to the parabrachial complex (PB), they synaptically engage distinct efferent nodes, the pre-locus coeruleus (pLC), and central lateral parabrachial nucleus (cLPBN), respectively. PB-projecting PVHPDYN neurons, like PVHMC4R neurons, receive input from interoceptive ARCAgRP neurons, respond to caloric state, and are sufficient and necessary to control food intake. This expands the CNS satiety circuitry to include two non-overlapping PVH to hindbrain circuits.

SUBMITTER: Li MM

PROVIDER: S-EPMC6508999 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits.

Li Monica M MM Madara Joseph C JC Steger Jennifer S JS Krashes Michael J MJ Balthasar Nina N Campbell John N JN Resch Jon M JM Conley Nicholas J NJ Garfield Alastair S AS Lowell Bradford B BB

Neuron 20190314 3

SIM1-expressing paraventricular hypothalamus (PVH) neurons are key regulators of energy balance. Within the PVHSIM1 population, melanocortin-4 receptor-expressing (PVHMC4R) neurons are known to regulate satiety and bodyweight, yet they account for only half of PVHSIM1 neuron-mediated regulation. Here we report that PVH prodynorphin-expressing (PVHPDYN) neurons, which notably lack MC4Rs, function independently and additively with PVHMC4R neur ...[more]

PMID: 30879785

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Project description:Most sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One means of transformation involves interactions between excitatory thalamocortical neurons that carry data to the cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate the flow of those data3-6. Although the importance of the TRN has long been recognised7-9, understanding of its cell types, their organization and their functional properties has lagged behind that of the thalamocortical systems they control. Here we address this by investigating the somatosensory and visual circuits of the TRN in mice. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated and physiologically distinct, and that connect reciprocally with independent thalamocortical nuclei through dynamically divergent synapses. Calbindin-expressing cells-located in the central core-connect with the ventral posterior nucleus, the primary somatosensory thalamocortical relay. By contrast, somatostatin-expressing cells-which reside along the surrounding edges of the TRN-synapse with the posterior medial thalamic nucleus, a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from the ventral posterior nucleus to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from the posterior medial thalamic nucleus to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in the intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. The processing specializations of these two somatosensory TRN subcircuits therefore appear to be tuned to the signals they carry-a primary central subcircuit tuned to discrete sensory events, and a higher-order edge subcircuit tuned to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide insights into how subnetworks of TRN neurons may differentially process distinct classes of thalamic information.

Dataset Information

The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits.

Publications

The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits.

Similar Datasets

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