PMID- 28209776 OWN - NLM STAT- MEDLINE DCOM- 20180412 LR - 20231115 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 114 IP - 10 DP - 2017 Mar 7 TI - Distance-dependent gradient in NMDAR-driven spine calcium signals along tapering dendrites. PG - E1986-E1995 LID - 10.1073/pnas.1607462114 [doi] AB - 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 measuring N-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. FAU - Walker, Alison S AU - Walker AS AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom. FAU - Neves, Guilherme AU - Neves G AUID- ORCID: 0000-0001-6463-6997 AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom. FAU - Grillo, Federico AU - Grillo F AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom. FAU - Jackson, Rachel E AU - Jackson RE AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom. FAU - Rigby, Mark AU - Rigby M AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom. FAU - O'Donnell, Cian AU - O'Donnell C AUID- ORCID: 0000-0003-2031-9177 AD - Department of Computer Science, University of Bristol, Bristol BS8 1UB, United Kingdom. FAU - Lowe, Andrew S AU - Lowe AS AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom. FAU - Vizcay-Barrena, Gema AU - Vizcay-Barrena G AD - Centre for Ultrastructural Imaging, Kings College London, London SE1 1UL, United Kingdom. FAU - Fleck, Roland A AU - Fleck RA AD - Centre for Ultrastructural Imaging, Kings College London, London SE1 1UL, United Kingdom. FAU - Burrone, Juan AU - Burrone J AD - Centre for Developmental Neurobiology, Kings College London, London SE1 1UL, United Kingdom; juan.burrone@kcl.ac.uk. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - MR/N026063/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170216 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 6384-92-5 (N-Methylaspartate) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Calcium Signaling MH - Dendritic Spines/*metabolism/ultrastructure MH - Embryo, Mammalian MH - Female MH - Gene Expression MH - Hippocampus/cytology/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Electron MH - Microtomy MH - N-Methylaspartate/metabolism MH - Neuronal Plasticity MH - Pregnancy MH - Primary Cell Culture MH - Pyramidal Cells/*metabolism/ultrastructure MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism MH - Synapses/physiology PMC - PMC5347575 OTO - NOTNLM OT - NMDA OT - calcium OT - dendrite OT - dendritic spine OT - hippocampus COIS- The authors declare no conflict of interest. EDAT- 2017/02/18 06:00 MHDA- 2018/04/13 06:00 PMCR- 2017/09/07 CRDT- 2017/02/18 06:00 PHST- 2017/02/18 06:00 [pubmed] PHST- 2018/04/13 06:00 [medline] PHST- 2017/02/18 06:00 [entrez] PHST- 2017/09/07 00:00 [pmc-release] AID - 1607462114 [pii] AID - 201607462 [pii] AID - 10.1073/pnas.1607462114 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E1986-E1995. doi: 10.1073/pnas.1607462114. Epub 2017 Feb 16.