Transient and Persistent Dynamics of CEA PKC-δ Neurons

Abstract

The central amygdala (CeA) has been shown to mediate a wide range of survival behaviors, but the circuitry that drives any specific behavior has remained elusive. Work manipulating genetically defined subsets of CeA neurons has proven fruitful for producing organized changes in behavior and is thought to define functional subsets in the CeA. Our work here focuses on the eating regulating Protein kinase C-delta (PKC-δ) expressing neurons. Proper regulation of eating behaviors is critical for survival, requiring both appropriate promotion and inhibition of food intake. PKC-δ neurons have been identified as a key regulator for eating suppression in anorexigenic conditions. However, not knowing the dynamics of these neurons during eating left a major knowledge gap in understanding how these neurons regulate food intake. Here, using in vivo microendoscope calcium imaging, we found that a subset of CeAPKC-δ neurons show a surprising transient activation that lasts only a few seconds during food approach. This transient activation is required for normal food intake in eating bouts. We also found that a subset of CeAPKC-δ neurons show persistent activation that lasts many minutes in response to satiation, either induced by intraperitoneal injection of cholecystokinin (CCK) or refeeding after fasting. The persistent neurons activated by CCK significantly overlap with those activated by LiCl, suggesting that some persistent populations might overlap. Our results also showed that these two subsets of CeAPKC-δ neurons with different dynamics are not related, suggesting that transient and persistent dynamics are represented by distinct neural ensembles that may play different roles in eating regulation. Finally, we show that these transient and persistent populations can be differentially regulated in two models of disordered eating, and that they may play a causative role in the connection between activity-based anorexia and wheel running.