Abstract
The basolateral amygdala (BLA) is reliably activated by psychological stress and hyperactive in conditions of pathological stress or trauma; however, subsets of BLA neurons are also readily activated by rewarding stimuli and can suppress fear and avoidance behaviours. The BLA is highly heterogeneous anatomically, exhibiting continuous molecular and connectivity gradients throughout the entire structure. A critical gap remains in understanding the anatomical specificity of amygdala subregions, circuits, and cell types explicitly activated by acute stress and how they are dynamically activated throughout stimulus exposure. Using a combination of topographical mapping for the activity-responsive protein FOS and fiber photometry to measure calcium transients in real-time, we sought to characterize the spatial and temporal patterns of BLA activation in response to a range of novel stressors (shock, swim, restraint, predator odour) and non-aversive, but novel stimuli (crackers, citral odour). We report four main findings: (1) the BLA exhibits clear spatial activation gradients in response to novel stimuli throughout the medial-lateral and dorsal-ventral axes, with aversive stimuli strongly biasing activation towards medial aspects of the BLA; (2) novel stimuli elicit distinct temporal activation patterns, with stressful stimuli exhibiting particularly enhanced or prolonged temporal activation patterns; (3) changes in BLA activity are associated with changes in behavioural state; and (4) norepinephrine enhances stress-induced activation of BLA neurons via the ß-noradrenergic receptor. Moving forward, it will be imperative to combine our understanding of activation gradients with molecular and circuit-specificity.
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Acknowledgements
This research was performed at the University of Calgary which is located on the unceded traditional territories of the people of the Treaty 7 region in Southern Alberta, which includes the Blackfoot Confederacy (including the Siksika, Piikuni, Kainai First Nations), the Tsuut’ina, and the Stoney Nakoda (including the Chiniki, Bearspaw, and Wesley First Nations). The City of Calgary is also home to Metis Nation of Alberta, Region III. We would like to acknowledge the Hotchkiss Brain Institute optogenetic core facility and the advanced microscopy facility for their technical support, and Min Qiao for her technical lab support. We also acknowledge the University of Calgary Health Sciences Animal Research Centre, specifically Vincent Hanson, Krista Jensen, and Brittany Munro. AAV.CaMKII.GCaMP6s.WPRE.SV40 (Addgene viral prep #107790-AAV9) was a gift from James M. Wilson.
Funding
This research was supported by operating funds to MNH from the Canadian Institutes of Health Research (CIHR). RJA received salary support from the Mathison Centre for Mental Health Research & Education and the Cumming School of Medicine. GNP received salary support from BranchOut Neurological Foundation, CIHR, and the Cumming School of Medicine. Support was also provided by NIH R01MH112355 (to M.R.B.) and NIH F31DA056148 (to A.K.M.). All authors declare no conflicts of interest.
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RA designed and conducted experiments, analyzed data, prepared figures, and wrote the manuscript. AM designed and conducted photometry experiments in mice and reviewed the manuscript. GP and MM provided advice in experimental design, conducted experiments, and reviewed the manuscript. SB conducted experiments and reviewed the manuscript. SK, IR, and AN conducted experiments. LM and TF developed optogenetic and photometry analysis tools and reviewed the manuscript. MB provided resources and advice in experimental design and reviewed the manuscript. JB provided advice in experimental design and reviewed the manuscript. MNH provided resources, developed and supervised the project, and contributed to and oversaw all data analyses, figure preparation, and writing and editing of the manuscript.
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MN Hill is an Associate Editor at Neuropsychopharmacology. The remaining authors have nothing to disclose.
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Aukema, R.J., Petrie, G.N., Matarasso, A.K. et al. Identification of a stress-responsive subregion of the basolateral amygdala in male rats. Neuropsychopharmacol. 49, 1989–1999 (2024). https://doi.org/10.1038/s41386-024-01927-x
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DOI: https://doi.org/10.1038/s41386-024-01927-x