A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function

Abstract

The amygdala is under inhibitory control from the cortex through the activation of local GABAergic interneurons. This inhibition is greatly diminished during heightened emotional states due to dopamine release. However, dopamine excites most amygdala interneurons, suggesting that this dopaminergic gate may be mediated by an unknown subpopulation of interneurons. We hypothesized that this gate is mediated by paracapsular intercalated cells, a subset of interneurons that are innervated by both cortical and mesolimbic dopaminergic afferents. Using transgenic mice that express GFP in GABAergic interneurons, we show that paracapsular cells form a network surrounding the basolateral complex of the amygdala. We found that they provide feedforward inhibition into the basolateral and the central amygdala. Dopamine hyperpolarized paracapsular cells through D1 receptors and substantially suppressed their excitability, resulting in a disinhibition of the basolateral and central nuclei. Suppression of the paracapsular system by dopamine provides a compelling neural mechanism for the increased affective behavior observed during stress or other hyperdopaminergic states.