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Near-Perfect Synaptic Integration by Na(v)1.7 in Hypothalamic Neurons Regulates Body Weight

Branco, T; Tozer, A; Magnus, CJ; Sugino, K; Tanaka, S; Lee, AK; Wood, JN; (2016) Near-Perfect Synaptic Integration by Na(v)1.7 in Hypothalamic Neurons Regulates Body Weight. Cell , 165 (7) pp. 1749-1761. 10.1016/j.cell.2016.05.019. Green open access

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Abstract

Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions.

Type: Article
Title: Near-Perfect Synaptic Integration by Na(v)1.7 in Hypothalamic Neurons Regulates Body Weight
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2016.05.019
Publisher version: http://dx.doi.org/10.1016/j.cell.2016.05.019
Language: English
Additional information: © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Neocortical Pyramidal Neurons, Sodium-Channels, Hippocampal-Neurons, Rna Interference, Agrp Neurons, Time-Course, Currents, Nucleus, Circuit, Hunger
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: http://discovery.ucl.ac.uk/id/eprint/1504837
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