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.
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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 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: | https://discovery.ucl.ac.uk/id/eprint/1504837 |
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