Hunger and memory; CRTC coordinates long-term memory with the physiological state, hunger

Area of Science:

• Neuroscience
• Molecular Biology
• Animal Behavior

Background:

• Memory formation is crucial for adaptive behavior.
• The molecular mechanisms of long-term memory (LTM) are known but their modulation by physiological states is unclear.
• Drosophila melanogaster serves as a model organism for studying memory.

Purpose of the Study:

• To investigate the effect of mild fasting on LTM formation in Drosophila.
• To elucidate the molecular mechanisms underlying fasting-induced LTM (fLTM).
• To explore the role of specific proteins and neural structures in fLTM.

Main Methods:

• Utilizing Drosophila melanogaster as a model organism.
• Employing single-cycle and multiple-cycle training paradigms to induce LTM.
• Analyzing the involvement of transcription factors CREB (cAMP response element-binding protein), CBP (CREB-binding protein), and CRTC (CREB-regulated transcription coactivator).
• Investigating gene expression in the mushroom body (MB).
• Examining insulin signaling pathways.

Main Results:

• Mild fasting facilitates LTM formation in Drosophila using single-cycle training.
• Fasting-induced LTM (fLTM) is dependent on CRTC, unlike canonical LTM which involves CBP.
• Gene expression in the mushroom body is required for LTM.
• Reduced insulin signaling during fasting activates CRTC, leading to fLTM.
• Flies adapt LTM formation mechanisms based on their hunger state.

Conclusions:

• Physiological states, such as hunger, can alter the molecular machinery of memory formation.
• Fasting-induced LTM formation in Drosophila offers a novel paradigm dependent on CRTC activation.
• The findings suggest that CRTC activation may be a target for improving memory deficits.