The cellular basis of distinct thirst modalities

Abstract

Fluid intake is an essential innate behavior mainly caused by two distinct types of thirst 1 – 3 . Increased blood osmolality induces osmotic thirst that drives animals to consume pure water. Conversely, the loss of body fluid induces hypovolemic thirst in which animals seek both water and minerals (salts) to recover blood volume. Circumventricular organs (CVOs) in the lamina terminalis (LT) are critical sites for sensing both types of thirst-inducing stimuli 4 – 6 . However, how different thirst modalities are encoded in the brain remains unknown. Here, we employed stimulus to cell-type mapping using single-cell RNA-seq (scRNA-seq) to determine the cellular substrate underlying distinct types of thirst. These studies revealed diverse excitatory and inhibitory neuron types in each CVO structure. Among them, we show that unique combinations of neuron types are activated under osmotic and hypovolemic stresses. These results elucidate the cellular logic underlying distinct thirst modalities. Furthermore, optogenetic gain-of-function in thirst-modality-specific cell types recapitulated water-specific and non-specific fluid appetite caused by the two distinct dipsogenic stimuli. Taken together, this study demonstrates that thirst is a multimodal physiological state, and that different thirst states are mediated by specific neuron types in the mammalian brain.

Deep parallel characterization of AAV tropism and AAV-mediated transcriptional changes via single-cell RNA sequencing

“…injection of euthasol (100 mg/kg). The following dissociation procedure of cortical tissue into a single-cell suspension was adapted with modifications from a previous report (Pool et al, 2020). Animals were transcardially perfused with ice-cold carbogenated (95% O2 and 5% CO2) NMDG-HEPES-ACSF (93 mM NMDG, 2.5 mM KCl, 1.2 mM NaH2PO4, 30 mM NaHCO3, 20 mM HEPES, 25 mM glucose, 5 mM Na L-ascorbate, 2 mM thiourea, 3 mM Na-pyruvate, 10 mM MgSO4, 1 mM CaCl2, 1 mM kynurenic acid Na salt, pH adjusted to 7.35 with 10N HCl, osmolarity range 300-310 mOsm).…”

Rapid development of vasopressin resistance in dietary K+ deficiency

“…Water balance in mammals is achieved by the coordinated actions of central thirst centers, the supraoptic nucleus in the hypothalamus, pituitary gland, and kidney loop of Henle and collecting duct. Small changes in plasma osmolality, detected in circumventricular organs (1,2), trigger the thirst reflex and the release of arginine vasopressin (AVP) from the posterior pituitary gland. AVP then acts on the collecting duct to activate aquaporin-2 (AQP2) water channels and to increase water absorption to restore osmolality before overt dehydration can ensue.…”

Neural Basis for Regulation of Vasopressin Secretion by Anticipated Disturbances in Osmolality

“…Recent studies have identified multiple molecularly- or anatomically-distinct neuronal populations in the LT that are involved in different aspects of water homeostasis (Oka et al, 2015b; Abbott et al, 2016; Allen et al, 2017; Matsuda et al, 2017; Augustine et al, 2018; Pool et al, 2020). In this study, we investigated the role of the LT neurons in mediating presystemic regulation of AVP neurons.…”