Distinct Neuronal Projections From the Hypothalamic Ventromedial Nucleus Mediate Glycemic and Behavioral Effects.

Abstract

The hypothalamic ventromedial nucleus (VMN) is implicated both in autonomic control of blood glucose and in behaviors including fear and aggression, but whether these divergent effects involve the same or distinct neuronal subsets and their projections is unknown. To address this question, we used an optogenetic approach to selectively activate the subset of VMN neurons that express neuronal nitric oxide synthase 1 (VMNNOS1 neurons) implicated in glucose counterregulation. We found that photoactivation of these neurons elicits 1) robust hyperglycemia achieved by activation of counterregulatory responses usually reserved for the physiological response to hypoglycemia and 2) defensive immobility behavior. Moreover, we show that the glucagon, but not corticosterone, response to insulin-induced hypoglycemia is blunted by photoinhibition of the same neurons. To investigate the neurocircuitry by which VMNNOS1 neurons mediate these effects, and to determine whether these diverse effects are dissociable from one another, we activated downstream VMNNOS1 projections in either the anterior bed nucleus of the stria terminalis (aBNST) or the periaqueductal gray (PAG). Whereas glycemic responses are fully recapitulated by activation of VMNNOS1 projections to the aBNST, freezing immobility occurred only upon activation of VMNNOS1 terminals in the PAG. These findings support previous evidence of a VMN→aBNST neurocircuit involved in glucose counterregulation and demonstrate that activation of VMNNOS1 neuronal projections supplying the PAG robustly elicits defensive behaviors.

• Authors: Chelsea L Faber, Miles E Matsen, Kevin R Velasco, Vincent Damian, Bao Anh Phan, Daniel Adam, Anthony Therattil, Michael W Schwartz, Gregory J Morton
• Journal: Diabetes (Diabetes) Vol. 67 Issue 12 Pg. 2518-2529 (12 2018) ISSN: 1939-327X [Electronic] United States
• PMID: 30257978 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• Insulin
• Glucagon
• Nitric Oxide Synthase Type I
• Glucose

Topics

• Animals
• Behavior, Animal (physiology)
• Glucagon (metabolism)
• Glucose (metabolism)
• Hypoglycemia (chemically induced, metabolism)
• Insulin
• Mice
• Neural Pathways (metabolism)
• Neurons (metabolism)
• Nitric Oxide Synthase Type I (metabolism)
• Optogenetics
• Periaqueductal Gray (metabolism)
• Septal Nuclei (metabolism)
• Ventromedial Hypothalamic Nucleus (metabolism)