Potentiated GABAergic neuronal activities in the basolateral amygdala alleviate stress‐induced depressive behaviors

Abstract

AimsMajor depressive disorder is a severe psychiatric disorder that afflicts ~17% of the world population. Neuroimaging investigations of depressed patients have consistently reported the dysfunction of the basolateral amygdala in the pathophysiology of depression. However, how the BLA and related circuits are implicated in the pathogenesis of depression is poorly understood.MethodsHere, we combined fiber photometry, immediate early gene expression (c‐fos), optogenetics, chemogenetics, behavioral analysis, and viral tracing techniques to provide multiple lines of evidence of how the BLA neurons mediate depressive‐like behavior.ResultsWe demonstrated that the aversive stimuli elevated the neuronal activity of the excitatory BLA neurons (BLACAMKII neurons). Optogenetic activation of CAMKII neurons facilitates the induction of depressive‐like behavior while inhibition of these neurons alleviates the depressive‐like behavior. Next, we found that the chemogenetic inhibition of GABAergic neurons in the BLA (BLAGABA) increased the firing frequency of CAMKII neurons and mediates the depressive‐like phenotypes. Finally, through fiber photometry recording and chemogenetic manipulation, we proved that the activation of BLAGABA neurons inhibits BLACAMKII neuronal activity and alleviates depressive‐like behavior in the mice.ConclusionThus, through evaluating BLAGABA and BLACAMKII neurons by distinct interaction, the BLA regulates depressive‐like behavior.

Regulation of depressive‐like behaviours by palmitoylation: Role of AKAP150 in the basolateral amygdala

“…Hyperexcitability of the BLA principal neurons plays a causal role in the chronic stress induced depressive‐like behaviours (Asim et al, 2023; Rosenkranz et al, 2010); therefore, we asked whether AKAP150 palmitoylation mediates the increased excitability of principal neurons in the BLA after CRS. To confirm this, we constructed a well‐characterized interference peptide Ht‐31 to disrupt the binding of AKAP150 and PKA according to previous reports (Kurihara et al, 2000; Vijayaraghavan et al, 1997).…”

Characterization of the neural circuitry of the auditory thalamic reticular nucleus and its potential role in salicylate-induced tinnitus

“…Like phantom limb pain ( De Ridder et al, 2011 ), hearing loss-induced tinnitus is marked by cortical reorganization and altered inhibition ( Rajan, 1998 ; Eggermont and Roberts, 2004 ; Weisz et al, 2007 ; Rauschecker et al, 2010 ; Roberts et al, 2010 ). Sodium salicylate-induced tinnitus, particularly, is tied to diminished auditory inhibition ( Wang et al, 2006 , 2008 ; Sun et al, 2009 ; Asim et al, 2023 ). Past studies have highlighted how noise exposure and aging can diminish auditory system inhibition ( Middleton et al, 2011 ; Llano et al, 2012 ; Asim et al, 2023 ), with salicylate directly attenuating inhibitory synaptic transmission in the auditory cortex and inferior colliculus—implicating weakened inhibition as a mechanism in tinnitus ( Wang et al, 2006 , 2008 , 2011 ).…”

“…Sodium salicylate-induced tinnitus, particularly, is tied to diminished auditory inhibition ( Wang et al, 2006 , 2008 ; Sun et al, 2009 ; Asim et al, 2023 ). Past studies have highlighted how noise exposure and aging can diminish auditory system inhibition ( Middleton et al, 2011 ; Llano et al, 2012 ; Asim et al, 2023 ), with salicylate directly attenuating inhibitory synaptic transmission in the auditory cortex and inferior colliculus—implicating weakened inhibition as a mechanism in tinnitus ( Wang et al, 2006 , 2008 , 2011 ). Given the pivotal role of TRN inhibition in auditory processing and its implications in the imbalance between excitation and inhibition in tinnitus, strategic modulation of this central inhibition could provide relief ( Rauschecker et al, 2010 ; Yang et al, 2011 ; Minen et al, 2014 ).…”

Microglial activation in the lateral amygdala promotes anxiety‐like behaviors in mice with chronic moderate noise exposure

“… 73 However, the mechanism underlying microglia‐mediated selective phagocytosis remains unclear and merits further investigation. The principal neurons in the LA are inhibited by local GABA interneurons 74 or inhibitory projections from the intercalated amygdala, 75 or even the auditory cortex. 76 However, whether microglia display pathway‐specific engulfment of inhibitory synapses requires cell‐type‐specific fluorescent labeling.…”