title: Facilitated glutamate release at Schaffer collateral to CA1 synapses has access to an exclusive population of NMDA receptors.
abstract: In order to explore short-term facilitation of the Schaffer collateral to CA1 synapse in mouse hippocampal brain slices, we measured the time course of the decay of the peak amplitude of successive EPSCs during progressive MK-801-dependent block (PMDB) of NMDAR responses to paired (R1 and R2) stimuli. We made the unexpected observation that the R2 response exhibited a slower PMDB decay constant than that of the R1 response. This indicated that the facilitated R2 response engages release sites with NMDARs that are protected from opening and consequent MK-801 block during the basal R1 response. We then utilized conditions that affect synaptic glutamate distribution to dissect the components of the distinct PMDB decay constants of the first and second of paired pulses. While extra-synaptic NMDARs and glutamate transporters appear to play only minor roles in the differences of the PMDB decay constant, we showed important roles for the R1 response itself and for glutamate diffusion in determining the PMDB decay constant of R2. We used a simple computational model with realistic parameters that allowed us to predict the time course of R2 decay based on the R1 decay time course.
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM 871311, United States; Physical Biosciences, Lawrence Berkeley National Laboratories, Berkeley, CA 94720, United States.
authors.forename: Chessa S
authors.initials: CS
authors.lastname: Scullin
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM 871311, United States; Biosciences, Sandia National Labs, Albuquerque, NM 87123, United States.
authors.forename: Adrian R B
authors.initials: AR
authors.lastname: Schiess
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM 871311, United States. Electronic address: dpartridge@salud.unm.edu.
authors.forename: L
authors.initials: L
authors.lastname: Donald Partridge
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D016018:Least-Squares Analysis; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques; D011336:Probability; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate
keywords: Hippocampal slice; Modeling; Mouse; NMDA; Synaptic transmission and plasticity