Non-invasive Strategies for Chronic Manipulation of DREADD-controlled Neuronal Activity

Abstract

Chemogenetic strategies have emerged as reliable tools for remote control of neuronal activity. Among these, designer receptors exclusively activated by designer drugs (DREADDs) have become the most popular chemogenetic approach used in modern neuroscience. Most studies deliver the ligand clozapine-N-oxide (CNO) using a single intraperitoneal injection, which is suitable for the acute activation/inhibition of the targeted neuronal population. There are, however, only a few examples of strategies for chronic modulation of DREADD-controlled neurons, the majority of which rely on the use of delivery systems that require surgical intervention. Here, we expand on two non-invasive strategies for delivering the ligand CNO to chronically manipulate neural population in mice. CNO was administered either by using repetitive (daily) eyedrops, or chronically through the animal’s drinking water. These non-invasive paradigms result in robust activation of the designer receptors that persisted throughout the CNO treatments. The methods described here offer alternatives for the chronic DREADD-mediated control of neuronal activity and may be useful for experiments designed to evaluate behavior in freely moving animals, focusing on less-invasive CNO delivery methods.

Oxytocin neurons enable social transmission of maternal behaviour

“…In both experimental ( Oxy-IRES-Cre virgins expressing DREADDi-mCherry) and control ( Oxy-IRES-Cre virgins expressing mCherry) cohorts, clozapine- N -oxide (CNO) was administered in the drinking water at a concentration of 25 mg l −1 (ref. 35 ). Five sugar pellets were added in each bottle to obscure the taste of CNO.…”

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“…Clozapine N‐oxide (CNO, 5 mg, Sigma) was initially dissolved with 1 ml saline (0.9%) and stored at 4℃ according to the method previously described. 23 CNO (3 mg kg −1 , i.p.) was administrated intraperitoneally per day from 10 to 14 days after incision surgery.…”

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