Details

Autor(en) / Beteiligte

• Kim, Jae-Ick
• Ganesan, Subhashree
• Luo, Sarah X
• Wu, Yu-Wei
• Park, Esther
• Huang, Eric J
• Chen, Lu
• Ding, Jun B

Titel

Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons

Ist Teil von

• Science (American Association for the Advancement of Science), 2015-10, Vol.350 (6256), p.102-106

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2015

Quelle

Science Online_科学在线

Beschreibungen/Notizen

• Midbrain dopamine neurons are an essential component of the basal ganglia circuitry, playing key roles in the control of fine movement and reward. Recently, it has been demonstrated that γ-aminobutyric acid (GABA), the chief inhibitory neurotransmitter, is co-released by dopamine neurons. Here, we show that GABA co-release in dopamine neurons does not use the conventional GABA-synthesizing enzymes, glutamate decarboxylases GAD65 and GAD67. Our experiments reveal an evolutionarily conserved GABA synthesis pathway mediated by aldehyde dehydrogenase 1a1 (ALDH1a1). Moreover, GABA co-release is modulated by ethanol (EtOH) at concentrations seen in blood alcohol after binge drinking, and diminished ALDH1a1 leads to enhanced alcohol consumption and preference. These findings provide insights into the functional role of GABA co-release in midbrain dopamine neurons, which may be essential for reward-based behavior and addiction.