title: Distance-dependent gradient in NMDAR-driven spine calcium signals along tapering dendrites.
abstract: Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuringN-methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end. Based on a compartmental model of spine calcium dynamics, we propose that this biased distribution in calcium signals is governed by a gradual, distance-dependent decline in spine size, which we visualized using serial block-face scanning electron microscopy. Our data describe a cell-autonomous feature of principal neurons, where tapering dendrites show an inverse distribution of spine size and NMDAR-driven calcium signals along dendritic trees, with important implications for synaptic plasticity rules and spine function.
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Alison S
authors.initials: AS
authors.lastname: Walker
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Guilherme
authors.identifier: 0000-0001-6463-6997
authors.initials: G
authors.lastname: Neves
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Federico
authors.initials: F
authors.lastname: Grillo
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Jackson
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Rigby
authors.affiliation: Department of Computer Science, University of Bristol, Bristol BS8 1UB, United Kingdom.
authors.forename: Cian
authors.identifier: 0000-0003-2031-9177
authors.initials: C
authors.lastname: O'Donnell
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lowe
authors.affiliation: Centre for Ultrastructural Imaging, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Gema
authors.initials: G
authors.lastname: Vizcay-Barrena
authors.affiliation: Centre for Ultrastructural Imaging, Kings College London, London SE1 1UL, United Kingdom.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Fleck
authors.affiliation: Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom; juan.burrone@kcl.ac.uk.
authors.forename: Juan
authors.initials: J
authors.lastname: Burrone
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008867:Microtomy; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity; D011247:Pregnancy; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D002118:Calcium
keywords: NMDA; calcium; dendrite; dendritic spine; hippocampus