Abstract
The central amygdala (CeA) is an important neuronal hub that integrates external sensory inputs and information about internal states to regulate a range of innate and learned behaviors, including fear learning and memory. Prior studies, leveraging robust fear conditioning assays, have delineated detailed circuit mechanisms underlying the acquisition and recall of fear memories. However, the specific molecular mechanisms underlying these processes in the CeA remain poorly understood. Here, we investigate the role of the clock output molecule mWAKE/ANKFN1 within the CeA of male mice in fear learning and memory. mWAKE is expressed in multiple neuronal subclusters in the lateral CeA. Surprisingly, mWAKE levels do not exhibit rhythmic expression in the CeA. In line with this observation, expression of the core clock genes PER2 and BMAL also does not cycle in the CeA. Consistent with prior studies, loss of mWAKE function increases intrinsic excitability of CeA neurons. Furthermore, conditional knock-out of mWAKE and chemogenetic activation of CeAmWAKE neurons impair fear learning and memory. Finally, we show that mWAKE levels in a subset of CeA neurons are reduced following fear conditioning. These findings suggest a potential molecular mechanism modulating the activity and function of CeA neurons in fear learning and memory.
Keywords:
amygdala; central amygdala; fear learning; fear memory; mWAKE.