Central role of regular firing neurons of centrolateral amygdala in affective behaviors

Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the Grik4 gene display anxiety, depression, social deficits, and disrupted amygdala excitab...

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Detalles Bibliográficos
Autores: García, Álvaro, Aller, María Isabel, Paternain, Ana V., Lerma Gómez, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/398866
Acceso en línea:http://hdl.handle.net/10261/398866
https://api.elsevier.com/content/abstract/scopus_id/105005586550
Access Level:acceso abierto
Palabra clave:Behavioral neuroscience
Cellular neuroscience
Descripción
Sumario:Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the Grik4 gene display anxiety, depression, social deficits, and disrupted amygdala excitability, inducing output circuit imbalance. To dissect the role of specific amygdala neuron populations, we created mice with extra copies of Grik4 and floxed native alleles. We normalized Grik4 dosage selectively in the basolateral amygdala (BLA) pyramidal cells via stereotaxic injection of AAV-CRE-GFP, using AAV-GFP as a control. Electrophysiological recordings from centrolateral amygdala (CeL) revealed that the normalization of Grik4 restored synaptic strength in regular but not late firing neurons. Behaviorally, this intervention reversed anxiety, depression, and social deficits, but not object recognition memory impairments. These results highlight the critical role of regular firing CeL neurons in affective disorders and suggest that targeting their activity may offer new strategies for treating anxiety and depression.