Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Byungjae Hwang
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Maria Reva
Institut Pasteur, Unit of Synapse and Circuit Dynamics, CNRS UMR, 3571 Paris, France; Sorbonne University, ED3C, Paris, France
Jieun Lee
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Byeong Eun Lee
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Youngeun Lee
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Eun Jeong Cho
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Minseok Jeong
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Seung Eun Lee
Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Kyungjae Myung
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea; Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
Ja-Hyun Baik
Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea
Jung-Hoon Park
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Jae-Ick Kim
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea; Corresponding author
Summary: 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.
