A corticoamygdalar pathway controls reward devaluation and depression using dynamic inhibition code.

Area of Science:

• Neuroscience
• Behavioral Science
• Psychiatry

Background:

• Reward devaluation adaptively regulates food intake, but the underlying cortical circuit mechanisms remain unclear, especially in depression.
• Understanding how neural pathways encode reward devaluation is crucial for addressing conditions like depression and obesity.

Purpose of the Study:

• To investigate the causal role of the anterior cingulate cortex (ACC) to basolateral amygdala (BLA) pathway in encoding reward devaluation.
• To explore how this neural circuit functions in healthy versus depressed states and its implications for depression treatment.

Main Methods:

• Utilized fiber photometry and imaging in ACC pyramidal neurons to observe neural activity related to reward.
• Employed chemogenetic techniques to manipulate neuronal activity within the ACC-BLA pathway in mouse models of depression.

Main Results:

• Identified a dynamic inhibition code in the ACC-BLA pathway controlling reward devaluation and depression.
• Observed weakened inhibition during satiation and further attenuation in depression models, leading to desensitized devaluation.
• Demonstrated that manipulating ACC-BLA pathway inhibition bidirectionally affects reward intake, obesity, and depression-like behaviors.

Conclusions:

• The ACC-BLA pathway encodes reward devaluation through dynamic inhibition, with blunted inhibition linked to depression.
• Targeting and enhancing inhibition within this corticoamygdalar circuit presents a potential therapeutic strategy for depression.