Astrocytes Mediate Long-lasting Synaptic Regulation of Ventral Tegmental Area Dopamine Neurons

Overview

Journal Nat Neurosci

Date 2022 Nov 18

PMID 36396976

Authors

Linda Maria Requie

Marta Gomez-Gonzalo

Michele Speggiorin

Francesca Manago

Marcello Melone

Mauro Congiu

Angela Chiavegato

Annamaria Lia

Micaela Zonta

Gabriele Losi

Vanessa Jorge Henriques

Arianna Pugliese

Giada Pacinelli

Giovanni Marsicano

Francesco Papaleo

Anna Lisa Muntoni

Fiorenzo Conti

Giorgio Carmignoto

Affiliations

Soon will be listed here.

Abstract

The plasticity of glutamatergic transmission in the ventral tegmental area (VTA) represents a fundamental mechanism in the modulation of dopamine neuron burst firing and phasic dopamine release at target regions. These processes encode basic behavioral responses, including locomotor activity, learning and motivated behaviors. Here we describe a hitherto unidentified mechanism of long-term synaptic plasticity in mouse VTA. We found that the burst firing in individual dopamine neurons induces a long-lasting potentiation of excitatory synapses on adjacent dopamine neurons that crucially depends on Ca elevations in astrocytes, mediated by endocannabinoid CB1 and dopamine D2 receptors co-localized at the same astrocytic process, and activation of pre-synaptic metabotropic glutamate receptors. Consistent with these findings, selective in vivo activation of astrocytes increases the burst firing of dopamine neurons in the VTA and induces locomotor hyperactivity. Astrocytes play, therefore, a key role in the modulation of VTA dopamine neuron functional activity.

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