Kim, Hyun-Jin Hwang, Byungjae Reva, Maria Lee, Jieun Lee, Byeong Eun Lee, Youngeun Cho, Eun Jeong Jeong, Minseok Lee, Seung Eun Myung, Kyungjae Baik, Ja-Hyun Park, Jung-Hoon Kim, Jae-Ick 2024-01-19T08:31:17Z 2024-01-19T08:31:17Z 2023-11-29 2023-10 2211-1247 https://pubs.kist.re.kr/handle/201004/113170 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. English Cell Press GABAergic-like dopamine synapses in the brain Article 10.1016/j.celrep.2023.113239 1 Cell Reports, v.42, no.10 Cell Reports 42 10 Y scie scopus 001096503000001 2-s2.0-85173776086 Cell Biology Cell Biology Article INHIBITORY SYNAPSES PARKINSONS-DISEASE SUBSTANTIA-NIGRA GABA SYNTHESIS RELEASE NEURONS GEPHYRIN TIME LOCALIZATION INNERVATION