title: Local dendritic activity sets release probability at hippocampal synapses.
abstract: The arrival of an action potential at a synapse triggers neurotransmitter release with a limited probability, p(r). Although p(r) is a fundamental parameter in defining synaptic efficacy, it is not uniform across all synapses, and the mechanisms by which a given synapse sets its basal release probability are unknown. By measuring p(r) at single presynaptic terminals in connected pairs of hippocampal neurons, we show that neighboring synapses on the same dendritic branch have very similar release probabilities, and p(r) is negatively correlated with the number of synapses on the branch. Increasing dendritic depolarization elicits a homeostatic decrease in p(r), and equalizing activity in the dendrite significantly reduces its variability. Our results indicate that local dendritic activity is the major determinant of basal release probability, and we suggest that this feedback regulation might be required to maintain synapses in their operational range.
authors.affiliation: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London WC1E6BT, UK. t.branco@ucl.ac.uk
authors.forename: Tiago
authors.initials: T
authors.lastname: Branco
authors.forename: Kevin
authors.initials: K
authors.lastname: Staras
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Darcy
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Goda
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D007091:Image Processing, Computer-Assisted; D046529:Microscopy, Electron, Transmission; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011336:Probability; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C073804:FM1 43; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds