{"id":"https://openalex.org/G2703381663","display_name":"Investigating the Exocytosis and Mobility of Single GABAergic Synaptic Vesicles Undergoing Spontaneous Release in Living Neurons Using a Real-time Three-dimensional Nanometer-accuracy Tracking Microscope","description":"Neurons communicate by releasing neurotransmitters from synaptic vesicles in presynaptic terminals. Recent studies have shown that the spontaneous (i.e., activity-independent) release of neurotransmitters plays an important role in neuronal function and in synaptic development. Moreover, impaired spontaneous release of synaptic vesicles has been implicated in several neurodevelopmental and psychiatric disorders. However, our understanding of spontaneous synaptic vesicle release is quite limited. Specifically, the exocytosis and mobility of single inhibitory synaptic vesicles undergoing spontaneous release has not been investigated, even though spontaneous release occurs frequently in mature inhibitory synapses and given that inhibitory synaptic transmission plays a critical role in maintaining the delicate balance between neuronal excitation and inhibition. Importantly, changes in this balance have been shown to underlie several neurological disorders, including autism spectrum disorder, schizophrenia, and epilepsy.\n\nRecently, we built an advanced real-time three-dimensional nanometer-accuracy tracking microscope, which allows us to track single synaptic vesicles loaded with a quantum dot (QD) with an accuracy of ~20-30 nm in three dimensions. Using this microscope, we have studied the exocytosis and mobility of single synaptic vesicles in living neurons and found that synaptic vesicles from the readily releasable pool (RRP) in excitatory synapses lie close to their fusion sites. Furthermore, we specifically labeled GABA-containing vesicles in inhibitory mature neurons and found that their evoked release is highly dynamic, providing rapid inhibitory synaptic transmission without synaptic fatigue in the neuronal network. However, the exocytosis and mobility of single inhibitory vesicles undergoing spontaneous release has not been investigated, limiting our knowledge regarding inhibitory neurotransmission and underlying neurological disorders. \n\nTherefore, we will test our working hypothesis that the exocytosis and/or mobility of GABAergic synaptic vesicles undergoing spontaneous release may differ from GABAergic vesicles undergoing evoked release. In this proposal, we will measure the exocytosis and mobility of single GABAergic vesicles undergoing spontaneous release in rat mature hippocampal and striatal neurons using real-time three-dimensional nanometer-accuracy tracking microscope, electron microscopy, and electrophysiology. We will also examine the release sites of spontaneously releasing GABAergic synaptic vesicles. Finally, we will examine whether and how neuronal activity affects the exocytosis and/or mobility of GABAergic synaptic vesicles labeled via spontaneous release. \n\nThese results will provide new important insights into differences between spontaneously releasing GABAergic vesicles and vesicles undergoing evoked release. Thus, this project will advance our understanding of inhibitory neurotransmission and facilitate the development of new therapeutic approaches for treating a number of neurological disorders associated with altered inhibitory 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Committee","doi":"10.13039/501100002920"},"funded_outputs":["https://openalex.org/W4309606058","https://openalex.org/W4385982134","https://openalex.org/W4388798821","https://openalex.org/W4417535338","https://openalex.org/W7116937367","https://openalex.org/W7134283183"],"funded_outputs_count":6,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":1180218.0,"currency":"HKD","amount_usd":150721.73,"amount_usd_basis":"annual_average","recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"General Research Fund","start_date":null,"end_date":"2026-02-28","start_year":2022,"end_year":2026,"landing_page_url":"https://cerg1.ugc.edu.hk/cergprod/scrrm00542.jsp?proj_id=16102322&old_proj_id=null&proj_title=&isname=&ioname=&institution=&subject=&pages=1&year=&theSubmit=16102322","doi":null,"provenance":"rgc_hk_project_enquiry","lead_investigator":{"given_name":"Hyokeun","family_name":"Park","orcid":null,"role_start":null,"affiliation":{"name":"The Hong Kong University of Science and Technology","country":null,"ids":null}},"co_lead_investigator":{"given_name":"Byung-Ho","family_name":"Kang","orcid":null,"role_start":null,"affiliation":{"name":null,"country":null,"ids":null}},"investigators":[{"given_name":"Wing Ho","family_name":"Yung","orcid":null,"role_start":null,"affiliation":{"name":null,"country":null,"ids":null}}],"works_api_url":"https://api.openalex.org/works?filter=awards.id:G2703381663","primary_topic":null,"topics":null,"institution_awarded":[{"id":"https://openalex.org/I200769079","display_name":"Hong Kong University of Science and Technology","ror":"https://ror.org/00q4vv597","country_code":"HK","type":"education","lineage":["https://openalex.org/I200769079"]}],"updated_date":"2026-10-16T03:01:01.000Z","created_date":"2026-07-13T04:54:40.000Z"}