Presynaptic inhibition of dopamine neurons controls optimistic bias.

Nobuhiro Yamagata,Hongyang Wu,Hiromu Tanimoto,Takahiro Ezaki,Takahiro Takahashi

doi:10.7554/elife.64907

Nobuhiro Yamagata, Hongyang Wu + Show 3 more

Open Access

https://doi.org/10.7554/elife.64907

Copy DOI

Journal: eLife	Publication Date: Jun 1, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Tohoku University, The University of Tokyo

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.

Highlights

Regulation of reward signaling in the brain is critical for maximizing positive outcomes and for avoiding futile costs of the behaviors at the same time
Dopamine neurons are primarily involved in reward processing (Brembs et al, 2002; Tobler et al, 2005; Liu et al, 2012; Ichinose et al, 2017)
To understand neuronal mechanisms for the regulation of reward processing, we here focused on gamma-aminobutyric acid (GABA) signaling in the protocerebral anterior medial (PAM) neurons

Summary

Introduction

Regulation of reward signaling in the brain is critical for maximizing positive outcomes and for avoiding futile costs of the behaviors at the same time. Dopamine input to the mushroom body (MB) causes changes in preference of a simultaneously presented odor by modulating the output of odor-representing MB intrinsic neurons, Kenyon cells (KCs) (Sejourneet al., 2011; Boto et al, 2014; Cohn et al, 2015; Owald et al, 2015; Louis et al, 2018; Hige et al, 2015; Bilz et al, 2020). Such associative presentations of odor and electric shocks were reported to change the activity of MB-projecting dopamine neurons (Riemensperger et al, 2005). Recent studies (Hattori et al, 2017; Cervantes-Sandoval et al, 2017; Takemura et al, 2017) suggest that axon terminals of the dopamine neurons locally integrate olfactory inputs to function as multiple independent units, though such subcellular reward processing has yet to be examined

Results and discussion

Materials and methods

Funding Funder