Presynaptic inhibition of dopamine neurons controls optimistic bias

Elife. 2021 Jun 1:10:e64907. doi: 10.7554/eLife.64907.

Abstract

Regulation of reward signaling in the brain is critical for appropriate judgement of the environment and self. In Drosophila, the protocerebral anterior medial (PAM) cluster dopamine neurons mediate reward signals. Here, we show that localized inhibitory input to the presynaptic terminals of the PAM neurons titrates olfactory reward memory and controls memory specificity. The inhibitory regulation was mediated by metabotropic gamma-aminobutyric acid (GABA) receptors clustered in presynaptic microdomain of the PAM boutons. Cell type-specific silencing the GABA receptors enhanced memory by augmenting internal reward signals. Strikingly, the disruption of GABA signaling reduced memory specificity to the rewarded odor by changing local odor representations in the presynaptic terminals of the PAM neurons. The inhibitory microcircuit of the dopamine neurons is thus crucial for both reward values and memory specificity. Maladaptive presynaptic regulation causes optimistic cognitive bias.

Keywords: D. melanogaster; GABA inhibition; dopamine; learning; memory; neuroscience; optimism; reward; subcellular calcium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal*
  • Brain / metabolism*
  • Cognition
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • GABAergic Neurons / metabolism*
  • Memory
  • Neural Inhibition*
  • Olfactory Perception
  • Presynaptic Terminals / metabolism*
  • Receptors, GABA-B / genetics
  • Receptors, GABA-B / metabolism
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism
  • Reward*
  • Smell
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Drosophila Proteins
  • Receptors, GABA-B
  • Receptors, Metabotropic Glutamate
  • gamma-Aminobutyric Acid
  • Dopamine

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.