Work

Enhancing mPFC to BLA information transmission through chemical genetics to improve exploratory behavior in chronic stress rats

Year: 2025

Type: article

Abstract: The pathogenesis of depression is fundamentally linked to the dysregulation of neural circuit structure and function. Notably, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) are critical brain regions in the regulation of depression-related behaviors. Depressed rats exhibited attenuated messaging between the mPFC and BLA, along with abnormally enhanced theta oscillations in the BLA during the execution of an exploratory task. However, whether specific activation of the mPFC improves exploratory behavior in rats and whether recovery of exploratory behavior is mediated by the mPFC-BLA neural circuitry is unknown. We modeled depression in rats using chronic unpredictable mild stimulation (CUMS) and employed chemogenetic approaches to selectively activate mPFC glutamatergic neurons in depressed rats. Through simultaneous monitoring of behavioral patterns and local field potentials (LFPs) in both mPFC and BLA during open-field exploration, we conducted comparative analyses between chemogenetically activated and sham-stimulated groups. Our investigation focused on theta oscillation dynamics, network connectivity strength, and interregional information transfer between mPFC and BLA during exploratory behavior. The results demonstrated that chemogenetic activation of mPFC not only ameliorated exploratory deficits in depressed rats but also enhanced mPFC-to-BLA information transfer while attenuating BLA theta oscillations. These findings suggest that the restoration of mPFC-to-BLA information flow may play a crucial role in improving exploratory behavior, thereby revealing a potential neural mechanism underlying depressive state modulation.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111335