mWAKE in the Central Amygdala Regulates Fear Learning and Memory.

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The central amygdala (CeA) is vital for processing fear learning and memory.
• Molecular mechanisms governing CeA function in fear memory remain unclear.

Purpose of the Study:

• Investigate the role of the clock output molecule mWAKE/ANKFN1 in the CeA of male mice during fear learning and memory.

Main Methods:

• Examined mWAKE expression patterns in CeA neuronal sub-clusters.
• Assessed the impact of mWAKE loss-of-function on neuronal excitability.
• Utilized conditional knockout and chemogenetics to study mWAKE's role in fear behavior.
• Measured mWAKE levels following fear conditioning.

Main Results:

• mWAKE is expressed in lateral CeA neurons but does not exhibit rhythmic expression, nor do core clock genes PER2 and BMAL.
• Loss of mWAKE increases CeA neuron excitability.
• Conditional knockout of mWAKE and chemogenetic activation of CeA^mWAKE neurons impair fear learning and memory.
• mWAKE levels decrease in specific CeA neurons after fear conditioning.

Conclusions:

• mWAKE plays a critical role in fear learning and memory by modulating CeA neuron activity.
• Non-rhythmic expression of mWAKE and clock genes in the CeA suggests a distinct function.
• Reduced mWAKE levels post-conditioning may represent a molecular mechanism for fear memory generation.