title: Dendritic position is a major determinant of presynaptic strength.
abstract: Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam and VU Medical Center, 1081 HV Amsterdam, Netherlands.
authors.forename: Arthur P H
authors.initials: AP
authors.lastname: de Jong
authors.forename: Sabine K
authors.initials: SK
authors.lastname: Schmitz
authors.forename: Ruud F G
authors.initials: RF
authors.lastname: Toonen
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
mesh_terms: D000200:Action Potentials; D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000378:metabolism / Q000502:physiology*