(131) - Determining the response of central amygdala dynorphin neurons to stress and pain

Abstract

The central amygdala (CeA) is a critical structure for emotional regulation in response to stress- and pain-related behaviors. Recently, much work has focused on deciphering the role distinct CeA cell-types play in appetitive and aversive behaviors. Here, we seek to dissect the function of CeA neurons expressing the neuropeptide dynorphin (Dyn+), the endogenous ligand for the kappa opioid receptor. To genetically identify Dyn+ neurons, we use a Cre-dependent tdTomato reporter mouse. Using this approach, we report distinct patterns of c-fos expression in these neurons following an acute 30-minute restraint stress paradigm and in response to a Complete Freund's Adjuvant inflammatory pain challenge. These studies suggest that CeA Dyn+ may not acutely respond to aversive stimuli. To examine the response of these neurons to chronic pain challenges we are using in vivo fiber photometry to monitor calcium signals over extended sampling periods. To test the sufficiency of this system to drive behaviors, we used in vivo optogenetics to photostimulate dynorphinergic neurons in the central amygdala in a real-time place preference paradigm. We find that selective photostimulation of dynorphinergic neurons in the central amygdala produces a frequency-dependent real-time aversion. This latter finding suggests that CeA Dyn+ neurons may be able to promote aversive behaviors. More work will be necessary to determine whether these neurons naturally drive such behavioral responses in times of stress or pain. Understanding the properties of the dynorphin/kappa opioid system in the context of chronic stress and pain will provide valuable insight into potential intervention strategies for these neurological and neuropsychiatric disorders.