title: Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons.
abstract: Schaffer collateral axons form excitatory synapses that are distributed across much of the dendritic arborization of hippocampal CA1 pyramidal neurons. Remarkably, AMPA-receptor-mediated miniature EPSP amplitudes at the soma are relatively independent of synapse location, despite widely different degrees of dendritic filtering. A progressive increase with distance in synaptic conductance is thought to produce this amplitude normalization. In this study we examined the mechanism(s) responsible for spatial scaling by making whole-cell recordings from the apical dendrites of CA1 pyramidal neurons. We found no evidence to suggest that there is any location dependence to the range of cleft glutamate concentrations found at Schaffer collateral synapses. Furthermore, we observed that release probability (Pr), paired-pulse facilitation and the size of the readily releasable vesicular pool are not dependent on synapse location. Thus, there do not appear to be any changes in the fundamental presynaptic properties of Schaffer collateral synapses that could account for distance-dependent scaling. On the other hand, two-photon uncaging of 4-methoxy-7-nitroindolinyl-caged L-glutamate onto isolated dendritic spines shows that the number of postsynaptic AMPA receptors per spine increases with distance from the soma. We conclude, therefore, that the main synaptic mechanism involved in the production of distance-dependent scaling of Schaffer collateral synapses is an elevated postsynaptic AMPA receptor density.
authors.affiliation: Neuroscience Center, LSUHSC, 2020 Gravier Street, New Orleans, LA 70112,USA. msmith19@lsuhsc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Graham C R
authors.initials: GC
authors.lastname: Ellis-Davies
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Magee
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D007736:Kynurenic Acid / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013569:Synapses / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: C440256:4-methoxy-7-nitroindolinyl-glutamate; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D007211:Indoles; D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013779:Tetrodotoxin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007736:Kynurenic Acid