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Nerve injury alters restraint-induced activation of the basolateral amygdala in male rats

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Abstract

The amygdala is critical for the production of appropriate responses towards emotional or stressful stimuli. It has a characteristic neuronal activation pattern to acute stressors. Chronic pain and acute stress have each been shown to independently modulate the activity of the amygdala. Few studies have investigated the effect of pain or injury, on amygdala activation to acute stress. This study investigated the effects of a neuropathic injury on the activation response of the amygdala to an acute restraint stress. Chronic constriction injury of the right sciatic nerve (CCI) was used to create neuropathic injury and a single brief 15-min acute restraint was used as an emotional/psychological stressor. All rats received cholera toxin B (CTB) retrograde tracer injections into the medial prefrontal cortex (mPFC) to assess if the amygdala to mPFC pathway was specifically regulated by the combination of neuropathic injury and acute stress. To assess differential patterns of activity in amygdala subregions, cFos expression was used as a marker for “acute”, restraint triggered neuronal activation, and FosB/ΔFosB expression was used to reveal prolonged neuronal activation/sensitisation triggered by CCI. Restraint resulted in a characteristic increase in cFos expression in the medial amygdala, which was not altered by CCI. Rats with a CCI showed increased cFos expression in the basolateral amygdala (BLA), in response to an acute restraint stress, but not in neurons projecting to the prefrontal cortex. Further, CCI rats showed an increase in FosB/ΔFosB expression which was exclusive to the BLA. This increase likely reflects sensitisation of the BLA as a consequence of nerve injury which may contribute to heightened sensitivity of BLA neurons to acute emotional/ psychological stressors.

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Abbreviations

CCI:

Chronic constriction injury of the right sciatic nerve

CTB:

Cholera toxin B

mPFC:

Medial prefrontal cortex

BLA:

Basolateral amygdala

CeA:

Central amygdala

MeA:

Medial amygdala

PFA:

4% Paraformaldehyde acetate-borate buffer

PBS:

0.1 M phosphate-buffered saline

NHS:

10% Normal horse serum

DAB:

3, 3-Diaminobenzidine tetrahydrochloride

CRF:

Corticosterone releasing factor (CRF)

GR:

Glucocorticoid receptor

LC:

Locus coeruleus

NTS:

Nucleus of the solitary tract

Nacc:

Nucleus accumbens

vCA1:

Ventral CA1

SNI:

Spared nerve injury

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Kang, J.W.M., Mor, D. & Keay, K.A. Nerve injury alters restraint-induced activation of the basolateral amygdala in male rats. Brain Struct Funct 226, 1209–1227 (2021). https://doi.org/10.1007/s00429-021-02235-6

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