title: Fast vesicle recycling supports neurotransmission during sustained stimulation at hippocampal synapses.
abstract: High-frequency induced short-term synaptic depression is a common feature of central synapses in which synaptic responses rapidly decrease to a sustained level. A limitation in the availability of release-ready vesicles is thought to be a major factor underlying this phenomenon. Here, we studied the kinetics of vesicle reavailability and reuse during synaptic depression at hippocampal synapses. High-intensity stimulation of neurotransmitter release was induced by hyperosmolarity, high potassium, or action potential firing at 30 Hz to produce synaptic depression. Under these conditions, synaptic transmission rapidly depressed to a plateau level that was typically 10-40% of the initial response and persisted at this level for at least 5 min regardless of the developmental stage of synapses. This nondeclining phase of transmission was partly sustained by fast recycling and reuse of synaptic vesicles even after minutes of stimulation. Simultaneous electrical recording of postsynaptic responses and styryl dye destaining showed that after an initial round of exocytosis, vesicles were available for reuse with a delay between 1 and 3 sec during 30 Hz action potential or hypertonicity-induced stimulation. During these stimulation paradigms, there was a limited mobilization of vesicles from the reserve pool. During 10 Hz stimulation, however, the extent of vesicle reuse was minimal during the first 20 sec. These results suggest a role for fast vesicle recycling as a functional homeostatic mechanism that prevents vesicle depletion and maintains synaptic responses in the face of intense stimulation.
authors.affiliation: Center for Basic Neuroscience and Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.
authors.forename: Yildirim
authors.initials: Y
authors.lastname: Sara
authors.forename: Marina G
authors.initials: MG
authors.lastname: Mozhayeva
authors.forename: Xinran
authors.initials: X
authors.lastname: Liu
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004558:Electric Stimulation; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006982:Hypertonic Solutions / Q000494:pharmacology; D007700:Kinetics; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D006982:Hypertonic Solutions; D011188:Potassium; D002118:Calcium