# The acid-sensing ion channel 1a modulates anxiety- and depression-related behaviors via its influencing on the activity of corticotropin-releasing hormone-expressing neurons in the hypothalamic paraventricular nucleus in male mice

## TL;DR

This study shows that ASIC1a in the brain affects anxiety and depression by influencing CRH neurons in male mice.

## Contribution

The study reveals a new mechanism by which ASIC1a modulates stress-related behaviors through CRH neurons in the PVN.

## Key findings

- ASIC1a is co-expressed with CRH in the hypothalamic paraventricular nucleus.
- Downregulating ASIC1a reduces HPA axis activity and improves anxiety and depression.
- ASIC1a activation increases CRH expression via Ca2+/CaMKII/c-Fos signaling.

## Abstract

A variety of studies show the involvement of acid-sensing ion channel 1a (ASIC1a) in the modulation of stress, however, the precise underlying mechanisms remain unclear. In this study, we provided evidence that ASIC1a, the Ca2+-permeable cationic ion channel, was co-expressed with corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN). Downregulation of ASIC1a in the PVN CRH neuron decreased the hypothalamic-pituitary-adrenal (HPA) axis activity, which further ameliorated anxiety- and depression-related behaviors by reducing CRH neuron activity. In vitro, activation of ASIC1a elevated the intracellular Ca2+ concentration and promoted the expression of CRH by activating Ca2+/CaMKII/c-Fos signaling pathways. This study reveals a novel mechanism of the modulation of negative mood by ASIC1a and suggests a potential novel therapeutic target for stress-related diseases.