Anxiety-like behavior is modulated by a discrete subpopulation of interneurons in the basolateral amygdala

Abstract

The basolateral amygdala (BL) is a putative site for regulating anxiety, where inhibition and excitation respectively lead to decreases and increases in anxiety-like behaviors. The BL contains local networks of GABAergic interneurons that are subdivided into classes based on neurochemical content, and are hypothesized to regulate unique functional responses of local glutamatergic projection neurons. Recently it was demonstrated that lesioning a portion of the BL interneuronal population, those interneurons that express neurokinin1 receptors (NK1r), resulted in anxiety-like behavior. In the current study, these NK1r expressing cells of the BL are further phenotypically characterized, demonstrating approximately 80% co-expression with GABA thus confirming them as GABAergic interneurons. These NK1r interneurons also co localize with two distinct populations of BL interneurons as defined by the neuropeptide content. 41.8% of the NK1r positive cells are also positive for neuropeptide Y (NPY) and 39.7% of the NK1r positive cells are also positive for cholecystokinin (CCK). In addition to enhancing the phenotypic characterization, the extent to which the NK1r cells of amygdala nuclei contribute to anxiety-like responses was also investigated. Lesioning the NK1r expressing interneurons, with a stable form of substance P (SSP; the natural ligand for NK1r) coupled to the targeted toxin saporin (SAP), in the anterior and posterior divisions of the BL was correlated to increased anxiety-like behaviors compared to baseline and control treated rats. Furthermore the phenotypic and regional selectivity of the lesions was also confirmed.

Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

“…Extensive neurodegeneration was present in the CRM-treated group, in all limbic structures studied, which probably explains the amygdala and hippocampal volume reduction. In addition, spontaneous inhibitory activity in the BLA was severely reduced in the CRM-treated group, and, consistent with the view that impaired inhibition in the BLA leads to anxiety Truitt et al, 2009;Zhou et al, 2010), anxiety-like behavior was significantly increased (behavioral abnormalities after nerve agent exposure are reviewed in Aroniadou-Anderjaska et al, 2016). The synergistic neuroprotective effect seen when CRM was combined with LY293558 can probably be attributed in large part to the NMDA receptor antagonistic properties of CRM, but other mechanisms may also be involved to a lesser extent.…”

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

“…Our evidence that increases in anxiety-like behavior are associated with deficits to the GABAergic system in the BLA is corroborated by previous studies demonstrating that the selective loss of GABAergic interneurons in the BLA contributes to anxiogenic behaviors (295). Likewise, we propose that impaired inhibition in the CAl region of the hippocampus may be the underlying cause of memory deficits following mTBI.…”

Pleasurable behaviors reduce stress via brain reward pathways

“…Neuronal activity in the amygdala, including the BLA, is altered in humans and other animals while they are engaging in pleasurable behaviors, including eating ap- petizing foods (20)(21)(22)(23). The amygdala is also activated in humans and other animals during stress (24,25), and the BLA subregion is implicated in neuroendocrine and behavioral stress responses (26)(27)(28). We therefore asked whether neural activity in the BLA is necessary for the stress-blunting effect.…”