Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus

AK Sutton, H Pei, KH Burnett, MG Myers… - Journal of …, 2014 - Soc Neuroscience
AK Sutton, H Pei, KH Burnett, MG Myers, CJ Rhodes, DP Olson
Journal of Neuroscience, 2014Soc Neuroscience
The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of
Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical
roles in the control of food intake and energy homeostasis. The roles of specific PVH
neuronal subtypes in energy balance have yet to be defined, however. The PVH contains
nitric oxide synthase-1 (Nos1)-expressing (Nos1PVH) neurons of unknown function; these
represent a subset of the larger population of Sim1-expressing PVH (Sim1PVH) neurons. To …
The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1PVH) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1PVH) neurons. To determine the role of Nos1PVH neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1PVH neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1PVH neurons suppresses feeding to a similar extent as Sim1PVH neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXTPVH) are a subset of Nos1PVH neurons. OXTPVH cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1PVH neurons; their activation fails to alter feeding, however. Thus, Nos1PVH neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXTPVH neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1PVH neurons in feeding regulation.
Soc Neuroscience