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Related Experiment Video

Updated: Aug 22, 2025

Aversive Associative Learning and Memory Formation by Pairing Two Chemicals in Caenorhabditis elegans
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Nutrient responding peptide hormone CCHamide-2 consolidates appetitive memory.

Nobuhiro Yamagata1, Yasuhito Imanishi1, Hongyang Wu1

  • 1Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Frontiers in Behavioral Neuroscience
|November 7, 2022
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Summary

Fruit fly peptide CCHamide-2 (CCHa2) links nutrient status to memory. CCHa2 signals are essential for consolidating appetitive long-term memory by acting on dopamine neurons, connecting energy homeostasis and reward pathways.

Keywords:
CCHa2CCHa2-RDrosophiladopaminememory consolidation

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Behavioral Genetics

Background:

  • CCHamide-2 (CCHa2) is an excitatory peptide found in arthropods.
  • In fruit flies, CCHa2 regulates endocrine signaling for development and energy balance.
  • Nutrient status influences the formation of odor-sugar associative long-term memory (LTM).

Purpose of the Study:

  • To investigate the role of CCHa2 in linking metabolic signals to memory formation.
  • To determine if CCHa2 is involved in the consolidation of appetitive memory.
  • To identify the neural circuits through which CCHa2 influences memory.

Main Methods:

  • Utilized mutant fruit fly strains to genetically disrupt CCHa2 function.
  • Employed post-learning thermal manipulation to control CCHa2-expressing cell activity.
  • Investigated the expression patterns of the CCHa2 receptor (CCHa2-R) in dopamine neurons.
  • Assessed the impact of CCHa2 disruption and manipulation on short-term memory (STM) and LTM.

Main Results:

  • Genetic disruption of CCHa2 abolished appetitive LTM but not STM.
  • Suppression of CCHa2 cells post-learning impaired LTM formation.
  • Activation of CCHa2 cells stabilized STM into LTM, particularly with non-nutritious sugar.
  • CCHa2-R is expressed in dopamine neurons crucial for reward-mediated LTM, and its expression is necessary for LTM.

Conclusions:

  • CCHa2 signaling is critical for the consolidation of appetitive LTM in fruit flies.
  • CCHa2 acts by conveying sugar nutrient signals to dopamine neurons involved in reward.
  • This study reveals a direct link between the brain's reward system and the endocrine system for long-term energy homeostasis.