Brain circuit dysfunction in specific symptoms of depression

Abstract

Since the depressive disorder manifests complex and diverse symptoms clinically, its pathological mechanism and therapeutic options are difficult to determine. In recent years, the advent of optogenetics, chemogenetics and viral tracing techniques, along with the well‐established rodent model of depression, has led to a shift in the focus of depression research from single molecules to neural circuits. In virtue of the powerful tools above, psychiatric disorder such as depression could be well related to the disfunction of brain's connection. Moreover, compelling studies also support that the diversity of depressive behaviour could be involved with the discrete changes in a distinct circuit of the brain. Therefore, summarising the differential changes of the neural circuits in mice with depression‐like behaviour may provide a better understanding of the causal relationships between neural circuit and depressive behaviour. Here, we focus on the changes in the neural circuitry underlying various depression‐like phenotypes, including motivation, despair, social avoidance and comorbid sequelae, which may provide an explanation to circuit‐specific discrepancy in depression‐like behaviour.

Optogenetic behavioral studies in depression research: A systematic review

“…Previous reviews have drawn conclusions that connect optogenetic interventions to the disease mechanisms of depression. 27 , 28 , 30 , 82 , 83 , 84 Most of these reviews provide qualitative analyses of a wide range of research results and discuss relevant brain targets involved in the mechanistic picture of depression. In addition, some articles discussed the accessibility of specific neuronal circuits for DBS.…”

“…Moreover, the question remains to what extend elucidated neuronal mechanisms in mice or rats are transferable to the human brain. 84 …”

Activation of Somatostatin-Expressing Neurons in the Lateral Septum Improves Stress-Induced Depressive-like Behaviors in Mice

“…Clinically, patients with depression experience diverse symptoms, such as despair, loss of pleasure, and anxiety [ 2 ]. One hypothesis is that these depressive symptoms are related to changes in different neural circuits regulating behaviors in response to stress and reward [ 4 ]. For example, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is involved in maladaptive responses to stress such as behavioral despair, circuit deficits in the reward system contribute to anhedonia, and changes in the amygdala may result in anxiety-like symptoms [ 1 , 3 , 5 ].…”

“…Decades of research have made substantial progress in uncovering the neural mechanisms of depression [ 1 , 2 , 3 ]. For instance, both clinical and basic studies suggest a crucial role of the limbic system in the regulation of depression [ 4 , 5 ]. Structural and functional alterations in multiple regions of the limbic system have been found in patients with major depressive disorder (MDD) [ 6 , 7 ].…”

EJN stress, brain and behaviour special issue

“…At the cerebral level, the effects of stress exposure are also highly circuit‐, region‐ and cell‐type specific (Lv et al, 2021). This is illustrated by the example of the bed nucleus of the stria terminalis (BNST), which is a highly stress‐responsive region in the brain involved in social behaviour (Flanigan & Kash, 2020) or the hippocampus and amygdala, where stress has highly impactful and lasting effects (de de Sousa Maciel et al, 2020; Ineichen et al, 2020; Saha et al, 2020).…”