Distinct CaMKII neurons in anterior cingulate cortex regulate anxiety-like behavior and appetite suppression in a model of inflammatory pain.

BACKGROUND: Chronic Inflammatory pain can lead to emotional abnormalities such as anxiety and a decreased appetite. However, the specific mechanisms underlying these abnormalities remain unclear. The anterior cingulate cortex (ACC), which plays a crucial role in integrating nociceptive perception and emotional responses to chronic inflammatory pain, is an ideal region for studying how pain influences anxiety and appetite. METHODS: In this study, we employed a variety of techniques, including fiber photometry recordings, neuroanatomical tract tracing, optogenetics, pharmacogenetics, and behavioral experiments, to investigate the neuronal circuits in the ACC of mice with chronic inflammatory pain. RESULTS: We identified two distinct CaMKII neurons in the ACC: one that projects to the basolateral amygdala (BLA) and is associated with anxiety-like behavior and another that projects to the nucleus accumbens (NAc) and regulates appetite suppression. Furthermore, we found that these two circuits are largely independent. And the intrinsic excitability and synaptic inputs in ACCCaMKII→BLA neurons and ACCCaMKII→NAc neurons are differentially influenced by chronic inflammatory pain. CONCLUSION: Our findings offer valuable insights into the circuit mechanisms in the ACC that regulate anxiety-like and appetite-suppression behaviors.