Clock neurons gate memory extinction in Drosophila.

Area of Science:

• Neuroscience
• Chronobiology
• Behavioral Science

Background:

• Memory suppression occurs when a conditioned stimulus (CS+) is repeatedly presented without an unconditioned stimulus (US).
• Extinction learning, which underlies memory suppression, requires multiple trials and results in transient memories, posing challenges for mechanistic understanding.

Purpose of the Study:

• To investigate the role of the circadian system in extinction memory formation.
• To identify specific neural circuits involved in regulating the transient nature of extinction memory.

Main Methods:

• Utilized genetic tools and the Drosophila circadian system.
• Inhibited clock neuron activity to assess effects on extinction memory.
• Performed calcium imaging (TRIC tool) to detect neural responses in specific neuron subsets (DN1s) during extinction training.

Main Results:

• Inhibition of clock neurons significantly blocked extinction memory formation.
• A subset of cryptochrome-positive dorsal neurons 1 (DN1s) and their downstream SIFamide neurons were identified as critical.
• Acute activation of DN1s facilitated extinction learning, evidenced by transient memory suppression, and specific DN1s showed neural responses to extinction training.

Conclusions:

• Clock neurons, particularly DN1s, act as a gating mechanism for extinction learning.
• Robust activation of DN1 clock neurons during extinction training may contribute to the transient nature of extinction memory.
• These findings link circadian clock function to the regulation of memory extinction.