ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms.

Autor: Mineur YS; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Mose TN; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Maibom KL; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Pittenger ST; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Soares AR; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.; Interdepartmental Neuroscience Program, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Wu H; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.; Interdepartmental Neuroscience Program, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Taylor SR; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.; Interdepartmental Neuroscience Program, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Huang Y; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.; Experimental Pathology Graduate Program, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA., Picciotto MR; Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA. marina.picciotto@yale.edu.; Interdepartmental Neuroscience Program, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA. marina.picciotto@yale.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2022 Dec; Vol. 27 (12), pp. 4918-4927. Date of Electronic Publication: 2022 Sep 01.
DOI: 10.1038/s41380-022-01749-7
Abstrakt: The balance between excitatory and inhibitory (E/I) signaling is important for maintaining homeostatic function in the brain. Indeed, dysregulation of inhibitory GABA interneurons in the amygdala has been implicated in human mood disorders. We hypothesized that acetylcholine (ACh) signaling in the basolateral amygdala (BLA) might alter E/I balance resulting in changes in stress-sensitive behaviors. We therefore measured ACh release as well as activity of calmodulin-dependent protein kinase II (CAMKII)-, parvalbumin (PV)-, somatostatin (SOM)- and vasoactive intestinal protein (VIP)-expressing neurons in the BLA of awake, behaving male mice. ACh levels and activity of both excitatory and inhibitory BLA neurons increased when animals were actively coping, and decreased during passive coping, in the light-dark box, tail suspension and social defeat. Changes in neuronal activity preceded behavioral state transitions, suggesting that BLA activity may drive the shift in coping strategy. In contrast to exposure to escapable stressors, prolonging ACh signaling with a cholinesterase antagonist changed the balance of activity among BLA cell types, significantly increasing activity of VIP neurons and decreasing activity of SOM cells, with little effect on CaMKII or PV neurons. Knockdown of α7 or β2-containing nAChR subtypes in PV and SOM, but not CaMKII or VIP, BLA neurons altered behavioral responses to stressors, suggesting that ACh signaling through nAChRs on GABA neuron subtypes contributes to stress-induced changes in behavior. These studies show that ACh modulates the GABAergic signaling network in the BLA, shifting the balance between SOM, PV, VIP and CaMKII neurons, which are normally activated coordinately during active coping in response to stress. Thus, prolonging ACh signaling, as occurs in response to chronic stress, may contribute to maladaptive behaviors by shifting the balance of inhibitory signaling in the BLA.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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