Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality

Angela Kim,Mark L Andermann,Chen Wu,Joseph C Madara,Bradford B Lowell

doi:10.7554/elife.66609

Abstract

Water balance, tracked by extracellular osmolality, is regulated by feedback and feedforward mechanisms. Feedback regulation is reactive, occurring as deviations in osmolality are detected. Feedforward or presystemic regulation is proactive, occurring when disturbances in osmolality are anticipated. Vasopressin (AVP) is a key hormone regulating water balance and is released during hyperosmolality to limit renal water excretion. AVP neurons are under feedback and feedforward regulation. Not only do they respond to disturbances in blood osmolality, but they are also rapidly suppressed and stimulated, respectively, by drinking and eating, which will ultimately decrease and increase osmolality. Here, we demonstrate that AVP neuron activity is regulated by multiple anatomically and functionally distinct neural circuits. Notably, presystemic regulation during drinking and eating are mediated by non-overlapping circuits that involve the lamina terminalis and hypothalamic arcuate nucleus, respectively. These findings reveal neural mechanisms that support differential regulation of AVP release by diverse behavioral and physiological stimuli.

Highlights

Rapid, anticipatory feedforward regulation is a common feature of many homeostatic circuits (Betley et al, 2015; Zimmerman et al, 2016; Augustine et al., 2018)
Consistent with this, we found that median preoptic nucleus (MnPO)/organum vasculosum lamina terminalis (OVLT) 175 inhibition caused a drop in the baseline activity of SONAVP neurons in water-restricted mice (Figure 2h)
Drinking behavior was not altered during the 299 experimental session or when tested in a separate setup (Figure 5q). These results demonstrate that excitatory and inhibitory inputs from the MnPO/OVLT are each responsible for pre- and post-ingestive drops in SONAVP neuron activity, respectively, and that both inputs are required for water-related presystemic responses of SONAVP neurons

Summary

Introduction

Anticipatory feedforward regulation is a common feature of many homeostatic circuits (Betley et al, 2015; Zimmerman et al, 2016; Augustine et al., 2018). Presystemic regulation of AVP release was first described in 1980, in a study using dehydrated dogs (Thrasher et al, 1981; Thrasher et al, 1987), and was later replicated in humans, monkeys, sheep, and rats (Arnauld and du Pont, 1982; Geelen et al, 1984; Blair-West et al, 1985; Huang et al, 2000). These studies demonstrated that drinking causes a rapid reduction in blood AVP levels and that this decrease precedes any detectable decrease in blood osmolality (i.e. it is presystemic). We used various circuit-mapping techniques, in vivo calcium imaging and opto- and chemo-genetics to identify and characterize the neural circuits mediating presystemic regulation of AVP neuron activity

Results

Discussion

Materials and Methods