GABAergic CaMKIIa1 Amygdala Output Attenuates Pain and Modulates Emotional-Motivational Behavior via Parabrachial Inhibition

19Citations
Citations of this article
35Readers
Mendeley users who have this article in their library.

Abstract

Pain and emotion are strongly regulated by neurons in the central nucleus of the amygdala (CeA), a major output of the limbic system; yet, the neuronal signaling pathways underlying this modulation are incompletely understood. Here, we characterized a subpopulation of CeA neurons that express the CaMKIIa gene (CeACAM neurons) and project to the lateral parabrachial nucleus (LPBN), a brainstem region known for its critical role in distributing nociceptive and other aversive signals throughout the brain. In male Sprague Dawley rats, we show that CeACAM-LPBN neurons are GABAergic and mostly express somatostatin. In anaesthetized rats, optogenetic stimulation of CeACAM-LPBN projections inhibited responses of LPBN neurons evoked by electrical activation of Ad- and C-fiber primary afferents; this inhibition could be blocked by intra-LPBN application of the GABAA receptor antagonist bicuculline. CeACAM-LPBN stimulation also dampened LPBN responses to noxious mechanical, thermal, and chemical stimuli. In behaving rats, optogenetic stimulation of CeACAM-LPBN projections attenuated nocifensive responses to mechanical pressure and radiant heat, disrupted the ability of a noxious shock to drive aversive learning, reduced the defensive behaviors of thigmotaxis and freezing, induced place preference, and promoted food consumption in sated rats. Thus, we suggest that CeACAM-LPBN projections mediate a form of analgesia that is accompanied by a shift toward the positive-appetitive pole of the emotional-motivational continuum. Since the affective state of pain patients strongly influences their prognosis, we envision that recruitment of this pathway in a clinical setting could potentially promote pain resilience and recovery.

Cite

CITATION STYLE

APA

Hogri, R., Teuchmann, H. L., Heinke, B., Holzinger, R., Trofimova, L., & Sandkühler, J. (2022). GABAergic CaMKIIa1 Amygdala Output Attenuates Pain and Modulates Emotional-Motivational Behavior via Parabrachial Inhibition. Journal of Neuroscience, 42(27), 5373–5388. https://doi.org/10.1523/JNEUROSCI.2067-21.2022

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free