Spine Neck Plasticity Controls Postsynaptic Calcium Signals through Electrical Compartmentalization

Dendritic spines have been proposed to function as electrical compartments for the active processing of local synaptic signals. However, estimates of the resistance between the spine head and the parent dendrite suggest that compartmentalization is not tight enough to electrically decouple the synapse. Here we show in acute hippocampal slices that spine compartmentalization is initially very weak, but increases dramatically upon postsynaptic depolarization. Using NMDA receptors as voltage sensors, we provide evidence that spine necks not only regulate diffusional coupling between spines and dendrites, but also control local depolarization of the spine head. In spines with high-resistance necks, presynaptic activity alone was sufficient to trigger calcium influx through NMDA receptors and R-type calcium channels. We conclude that calcium influx into spines, a key trigger for synaptic plasticity, is dynamically regulated by spine neck plasticity through a process of electrical compartmentalization.

[1]  T. Bliss,et al.  Single Synaptic Events Evoke NMDA Receptor–Mediated Release of Calcium from Internal Stores in Hippocampal Dendritic Spines , 1999, Neuron.

[2]  KM Harris,et al.  Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Bartlett W. Mel,et al.  Computational subunits in thin dendrites of pyramidal cells , 2004, Nature Neuroscience.

[4]  N. Kasthuri,et al.  Long-term dendritic spine stability in the adult cortex , 2002, Nature.

[5]  C. Koch,et al.  The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[7]  R. Yuste,et al.  Regulation of Spine Calcium Dynamics by Rapid Spine Motility Materials and Methods , 2022 .

[8]  J. Schiller,et al.  NMDA spikes in basal dendrites of cortical pyramidal neurons , 2000, Nature.

[9]  Bernardo L Sabatini,et al.  Timing and Location of Synaptic Inputs Determine Modes of Subthreshold Integration in Striatal Medium Spiny Neurons , 2007, The Journal of Neuroscience.

[10]  Roberto Araya,et al.  Sodium channels amplify spine potentials , 2007, Proceedings of the National Academy of Sciences.

[11]  Karel Svoboda,et al.  Locally dynamic synaptic learning rules in pyramidal neuron dendrites , 2007, Nature.

[12]  P. J. Sjöström,et al.  Dendritic excitability and synaptic plasticity. , 2008, Physiological reviews.

[13]  Mu-ming Poo,et al.  Shrinkage of Dendritic Spines Associated with Long-Term Depression of Hippocampal Synapses , 2004, Neuron.

[14]  Nace L. Golding,et al.  Compartmental Models Simulating a Dichotomy of Action Potential Backpropagation in Ca1 Pyramidal Neuron Dendrites , 2001, Journal of neurophysiology.

[15]  Yasushi Miyashita,et al.  Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons , 2001, Nature Neuroscience.

[16]  K. Svoboda,et al.  Imaging Calcium Concentration Dynamics in Small Neuronal Compartments , 2004, Science's STKE.

[17]  G. Ellis‐Davies,et al.  Structural basis of long-term potentiation in single dendritic spines , 2004, Nature.

[18]  Christof Koch,et al.  Biophysics of Computation: Information Processing in Single Neurons (Computational Neuroscience Series) , 1998 .

[19]  W Rall,et al.  Computational study of an excitable dendritic spine. , 1988, Journal of neurophysiology.

[20]  C Koch,et al.  The biophysical properties of spines as a basis for their electrical function: a comment on Kawato & Tsukahara (1983). , 1985, Journal of theoretical biology.

[21]  A. Medvedev,et al.  Criteria for the evaluation of the functional importance of endogenous analogues of pharmacological regulators , 2007, Biomeditsinskaia khimiia.

[22]  Karel Svoboda,et al.  NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines , 2005, The Journal of Neuroscience.

[23]  B. Sabatini,et al.  Nonlinear Regulation of Unitary Synaptic Signals by CaV2.3 Voltage-Sensitive Calcium Channels Located in Dendritic Spines , 2007, Neuron.

[24]  D. Johnston,et al.  Electrical and calcium signaling in dendrites of hippocampal pyramidal neurons. , 1998, Annual review of physiology.

[25]  C. Stevens,et al.  Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  P. Mermelstein,et al.  Unique properties of R-type calcium currents in neocortical and neostriatal neurons. , 2000, Journal of neurophysiology.

[27]  D W Tank,et al.  Direct Measurement of Coupling Between Dendritic Spines and Shafts , 1996, Science.

[28]  J. Connor,et al.  Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses , 1991, Nature.

[29]  B. Sakmann,et al.  Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  K. Svoboda,et al.  The Number of Glutamate Receptors Opened by Synaptic Stimulation in Single Hippocampal Spines , 2004, The Journal of Neuroscience.

[31]  Thomas G. Oertner,et al.  Optical induction of plasticity at single synapses reveals input-specific accumulation of αCaMKII , 2008, Proceedings of the National Academy of Sciences.

[32]  J. Lisman,et al.  Requirements for LTP induction by pairing in hippocampal CA1 pyramidal cells. , 1999, Journal of neurophysiology.

[33]  T. Török Electrogenic Na+/Ca2+-exchange of nerve and muscle cells , 2007, Progress in Neurobiology.

[34]  K. Harris,et al.  Slices Have More Synapses than Perfusion-Fixed Hippocampus from both Young and Mature Rats , 1999, The Journal of Neuroscience.

[35]  Karel Svoboda,et al.  ScanImage: Flexible software for operating laser scanning microscopes , 2003, Biomedical engineering online.

[36]  Karel Svoboda,et al.  Plasticity of calcium channels in dendritic spines , 2003, Nature Neuroscience.

[37]  J. Magee,et al.  State-Dependent Dendritic Computation in Hippocampal CA1 Pyramidal Neurons , 2006, The Journal of Neuroscience.

[38]  N. Toni,et al.  LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite , 1999, Nature.

[39]  J. Lisman,et al.  The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Roberto Araya,et al.  Dendritic spines linearize the summation of excitatory potentials , 2006, Proceedings of the National Academy of Sciences.

[41]  Johannes J. Letzkus,et al.  Requirement of dendritic calcium spikes for induction of spike‐timing‐dependent synaptic plasticity , 2006, The Journal of physiology.

[42]  B. Sakmann,et al.  Single Spine Ca2+ Signals Evoked by Coincident EPSPs and Backpropagating Action Potentials in Spiny Stellate Cells of Layer 4 in the Juvenile Rat Somatosensory Barrel Cortex , 2004, The Journal of Neuroscience.

[43]  R. Yuste,et al.  Linear Summation of Excitatory Inputs by CA1 Pyramidal Neurons , 1999, Neuron.

[44]  G. Collingridge,et al.  Interactions of 2,3‐benzodiazepines and cydothiazide at AMPA receptors: patch clamp recordings in cultured neurones and area CA1 in hippocampal slices , 1996, British journal of pharmacology.

[45]  W. Denk,et al.  Mechanisms of Calcium Influx into Hippocampal Spines: Heterogeneity among Spines, Coincidence Detection by NMDA Receptors, and Optical Quantal Analysis , 1999, The Journal of Neuroscience.

[46]  D Holcman,et al.  Diffusion in a dendritic spine: the role of geometry. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[47]  Bernardo L Sabatini,et al.  Neuronal Activity Regulates Diffusion Across the Neck of Dendritic Spines , 2005, Science.

[48]  A. Konnerth,et al.  NMDA Receptor-Mediated Subthreshold Ca2+ Signals in Spines of Hippocampal Neurons , 2000, The Journal of Neuroscience.