Optogenetic and chemogenetic insights into the neurocircuitry of depression‐like behaviour: A systematic review

Abstract

Major depressive disorder (MDD) and its treatment are challenges for global health. Optogenetics and chemogenetics are driving MDD research forward by unveiling causal relations between cell type-specific control of neurons and depressive-like behaviour in rodents. Using a systematic search process, in this review, a set of 43 original studies applying optogenetic or chemogenetic techniques in rodent models of depression was identified. Our aim was to provide an examination of all available studies elucidating central neuronal mechanisms leading to depressive-like behaviour in rodents and thereby unveiling the most promising routes for future research. A complex interacting network of relevant structures, in which central circuitries causally related to depressive-like behaviour are implicated, has been identified. As most relevant structures emerge: medial prefrontal cortex, anterior cingulate cortex, amygdala, nucleus accumbens, ventral tegmental area, hippocampus and raphe nuclei. Further evidence, though examined by only few studies, emerges for structures like the lateral habenula, or medial dorsal thalamus. Most of the identified brain areas have previously been associated with MDD neuropathology, but now evidence can be provided for causal pathological mechanisms within a complex cortico-limbic reward circuitry. However, the studies also show conflicting results concerning the 10 |

Prefrontal Disinhibition in Social Fear: A Vital Action of Somatostatin Interneurons

“…Although subtypes of cortical INs based on the expression of a single molecular marker may oversimplify the diversity of neural network organization (Kamigaki, 2019), this classification provides important opportunities to dissect cell-type-specific functions by recent innovative genetic tools. Optogenetics and chemogenetics are two of the most frequently used genetic techniques to specifically manipulate neuronal activity (Biselli et al, 2019). Optogenetics uses light-sensitive ion channels expressed in targeted cells allowing for neuronal depolarization or hyperpolarization with light illumination (Boyden et al, 2005), while chemogenetics uses designer receptors exclusively activated by designer drugs (DREADDs) expressed in targeted cells (Armbruster et al, 2007).…”

AMPA receptors mediate the pro-cognitive effects of electrical and optogenetic stimulation of the medial prefrontal cortex in antidepressant non-responsive Wistar–Kyoto rats

“…We also asked whether the antidepressant effect of DBS, in WKY rats, would be mimicked by optogenetic stimulation (OGS) at the same site in the mPFC. OGS has great potential as a technique to map out depression-relevant neural pathways ( Biselli et al, 2019 ; Cheng et al, 2020 ). Previous studies have reported antidepressant-like effects of OGS in mice subjected to chronic social defeat ( Bagot et al, 2015 ; Covington et al, 2010 ; Vialou et al, 2014 ), and in the forced swim or tail suspension test applied to normal mice (e.g.…”

Depression in focus: Insights from animal and human data, from molecular to behavioural analyses

“…This technical progress helped provide a better understanding of the pathophysiology of depression, and in particular establishing a causal link between changes in neuronal activity and behaviour. Biselli et al (2019) reviewed the recent studies using these approaches to understand depressive-like behaviours in rodents and highlighted their methodological limitations. Changes in several cortical and limbic brain structures, such as the prefrontal cortex, the amygdala, the nucleus accumbens and the hippocampal formation, have been associated with major depressive disorder (MDD).…”