Stress impacts corticoamygdalar connectivity in an age-dependent manner

Abstract

Stress is a socio-environmental risk factor for the development of psychiatric disorders, with the age of exposure potentially determining the outcome. Several brain regions mediate stress responsivity, with a prominent role of the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) and their reciprocal inhibitory connectivity. Here we investigated the impact of stress exposure during adolescence and adulthood on the activity of putative pyramidal neurons in the BLA and corticoamygdalar plasticity using in vivo electrophysiology. 155 male Sprague-Dawley rats were subjected to a combination of footshock/restraint stress in either adolescence (postnatal day 31–40) or adulthood (postnatal day 65–74). Both adolescent and adult stress increased the number of spontaneously active putative BLA pyramidal neurons 1–2 weeks, but not 5–6 weeks post stress. High-frequency stimulation (HFS) of BLA and mPFC depressed evoked spike probability in the mPFC and BLA, respectively, in adult but not adolescent rats. In contrast, an adult-like BLA HFS-induced decrease in spike probability of mPFC neurons was found 1–2 weeks post-adolescent stress. Changes in mPFC and BLA neuron discharge were found 1–2 weeks post-adult stress after BLA and mPFC HFS, respectively. All these changes were transient since they were not found 5–6 weeks post adolescent or adult stress. Our findings indicate that stress during adolescence may accelerate the development of BLA–PFC plasticity, probably due to BLA hyperactivity, which can also disrupt the reciprocal communication of BLA–mPFC after adult stress. Therefore, precocious BLA–mPFC connectivity alterations may represent an early adaptive stress response that ultimately may contribute to vulnerability to adult psychiatric disorders.

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Fig. 1: Adolescent and adult stress increased the number of spontaneously active putative pyramidal neurons in the BLA.
Fig. 2: Adolescent stress induces adult-like inhibitory plasticity of BLA to PFC neurons whereas adult stress impairs it.
Fig. 3: Adult stress impairs the inhibitory plasticity in the mPFC to BLA neuron projection 1–2 weeks post stress.
Fig. 4: A schematic representation of adolescent and adult stress impact on mPFC–BLA connectivity.

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Acknowledgements

The authors wish to thank Niki MacMurdo and Christy Smolak for technical assistance.

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DLU: conceptualization, methodology, data acquisition, formal analysis, interpretation, and writing—original draft. FVGs: conceptualization, methodology, data acquisition, interpretation, and writing—review and editing. AAG: conceptualization, resources, interpretation, writing—review and editing, supervision, and funding acquisition.

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Correspondence to Daniela L. Uliana.

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Uliana, D.L., Gomes, F.V. & Grace, A.A. Stress impacts corticoamygdalar connectivity in an age-dependent manner. Neuropsychopharmacol. (2020). https://doi.org/10.1038/s41386-020-00886-3

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