GABAergic-like dopamine synapses in the brain

Hyun Jin Kim, Byungjae Hwang, Maria Reva, Jieun Lee, Byeong Eun Lee, Youngeun Lee, Eun Jeong Cho, Minseok Jeong, Seung Eun Lee, Kyungjae Myung, Ja Hyun Baik, Jung Hoon Park, Jae Ick Kim

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson's disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.

Original languageEnglish
Article number113239
JournalCell Reports
Volume42
Issue number10
DOIs
Publication statusPublished - 2023 Oct 31

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

  • CP: Neuroscience
  • GABAergic-like dopamine synapse
  • Parkinson's disease
  • dopamine synapse
  • dopamine-GABA co-transmission

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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