Dendritic Spines as Tunable Regulators of Synaptic Signals

Neurons are perpetually receiving vast amounts of information in the form of synaptic input from surrounding cells. The majority of input occurs at thousands of dendritic spines, which mediate excitatory synaptic transmission in the brain, and is integrated by the dendritic and somatic compartments of the postsynaptic neuron. The functional role of dendritic spines in shaping biochemical and electrical signals transmitted via synapses has long been intensely studied. Yet, many basic questions remain unanswered, in particular regarding the impact of their nanoscale morphology on electrical signals. Here, we review our current understanding of the structure and function relationship of dendritic spines, focusing on the controversy of electrical compartmentalization and the potential role of spine structural changes in synaptic plasticity.

[1]  J Rinzel,et al.  Branch input resistance and steady attenuation for input to one branch of a dendritic neuron model. , 1973, Biophysical journal.

[2]  E. Fifková,et al.  Stimulation-induced changes in dimensions of stalks of dendritic spines in the dentate molecular layer , 1981, Experimental Neurology.

[3]  J. Wickens Electrically coupled but chemically isolated synapses: Dendritic spines and calcium in a rule for synaptic modification , 1988, Progress in Neurobiology.

[4]  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.

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

[6]  H. T. Chang,et al.  Cortical neurons with particular reference to the apical dendrites. , 1952, Cold Spring Harbor symposia on quantitative biology.

[7]  Amanda L. Loshbaugh,et al.  Labelling and optical erasure of synaptic memory traces in the motor cortex , 2015, Nature.

[8]  S. B. Kater,et al.  Independent regulation of calcium revealed by imaging dendritic spines , 1991, Nature.

[9]  Roberto Araya,et al.  The spine neck filters membrane potentials , 2006, Proceedings of the National Academy of Sciences.

[10]  Nelson Spruston,et al.  Synaptic amplification by dendritic spines enhances input cooperativity , 2012, Nature.

[11]  Bernardo L Sabatini,et al.  Live-cell superresolution imaging by pulsed STED two-photon excitation microscopy. , 2013, Biophysical journal.

[12]  S. Ramón y. Cajal,et al.  Structure and connections of neurons. , 1952, Bulletin of the Los Angeles Neurological Society.

[13]  Benjamin Schmid,et al.  A high-level 3D visualization API for Java and ImageJ , 2010, BMC Bioinformatics.

[14]  J. Herms,et al.  Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities , 2015, Acta Neuropathologica.

[15]  J. Bourne,et al.  Local Zones of Endoplasmic Reticulum Complexity Confine Cargo in Neuronal Dendrites , 2012, Cell.

[16]  Karel Svoboda,et al.  Experience-dependent and cell-type-specific spine growth in the neocortex , 2006, Nature.

[17]  Yi Zuo,et al.  Spine Neck Plasticity Controls Postsynaptic Calcium Signals through Electrical Compartmentalization , 2008, The Journal of Neuroscience.

[18]  Carlo Sala,et al.  Dendritic spines: the locus of structural and functional plasticity. , 2014, Physiological reviews.

[19]  K. Svoboda,et al.  Principles of Two-Photon Excitation Microscopy and Its Applications to Neuroscience , 2006, Neuron.

[20]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[21]  T. Bonhoeffer,et al.  Live-cell imaging of dendritic spines by STED microscopy , 2008, Proceedings of the National Academy of Sciences.

[22]  E. Kandel,et al.  Transient expansion of synaptically connected dendritic spines upon induction of hippocampal long-term potentiation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  T. Südhof Neuroligins and neurexins link synaptic function to cognitive disease , 2008, Nature.

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

[25]  Ryohei Yasuda,et al.  Imaging spatiotemporal dynamics of neuronal signaling using fluorescence resonance energy transfer and fluorescence lifetime imaging microscopy , 2007, Current Opinion in Neurobiology.

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

[27]  T. Poggio,et al.  A theoretical analysis of electrical properties of spines , 1983, Proceedings of the Royal Society of London. Series B. Biological Sciences.

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

[29]  T. Bonhoeffer,et al.  Bidirectional Activity-Dependent Morphological Plasticity in Hippocampal Neurons , 2004, Neuron.

[30]  Kevan A. C. Martin,et al.  Protracted Synaptogenesis after Activity-Dependent Spinogenesis in Hippocampal Neurons , 2007, The Journal of Neuroscience.

[31]  G. Ellis‐Davies,et al.  In vivo two‐photon uncaging of glutamate revealing the structure–function relationships of dendritic spines in the neocortex of adult mice , 2011, The Journal of physiology.

[32]  Mriganka Sur,et al.  Structural and Molecular Remodeling of Dendritic Spine Substructures during Long-Term Potentiation , 2014, Neuron.

[33]  Dejan Zecevic,et al.  Electrical behaviour of dendritic spines as revealed by voltage imaging , 2015, Nature Communications.

[34]  U Valentin Nägerl,et al.  Two-photon excitation STED microscopy in two colors in acute brain slices. , 2013, Biophysical journal.

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

[36]  K. Svoboda,et al.  Spine growth precedes synapse formation in the adult neocortex in vivo , 2006, Nature Neuroscience.

[37]  S. Hell,et al.  Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[38]  E. G. Gray,et al.  Electron Microscopy of Synaptic Contacts on Dendrite Spines of the Cerebral Cortex , 1959, Nature.

[39]  Heikki Rauvala,et al.  [The dynamic synapse]. , 2003, Duodecim; laaketieteellinen aikakauskirja.

[40]  Mark J. Schnitzer,et al.  Impermanence of dendritic spines in live adult CA1 hippocampus , 2015, Nature.

[41]  W. Denk,et al.  Two-photon scanning photochemical microscopy: mapping ligand-gated ion channel distributions. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[42]  F. Engert,et al.  Dendritic spine changes associated with hippocampal long-term synaptic plasticity , 1999, Nature.

[43]  A. Peters,et al.  The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. , 1970, The American journal of anatomy.

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

[45]  J. Simon Wiegert,et al.  Long-term depression triggers the selective elimination of weakly integrated synapses , 2013, Proceedings of the National Academy of Sciences.

[46]  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.

[47]  F. Crick Do dendritic spines twitch? , 1982, Trends in Neurosciences.

[48]  Martin Fuhrmann,et al.  Long-Term In Vivo Imaging of Dendritic Spines in the Hippocampus Reveals Structural Plasticity , 2014, The Journal of Neuroscience.

[49]  K. Harris,et al.  Ultrastructural Analysis of Hippocampal Neuropil from the Connectomics Perspective , 2010, Neuron.

[50]  Rafael Yuste,et al.  Space matters: local and global dendritic Ca2+ compartmentalization in cortical interneurons , 2005, Trends in Neurosciences.

[51]  Javier DeFelipe,et al.  The dendritic spine story: an intriguing process of discovery , 2015, Front. Neuroanat..

[52]  S. Hell,et al.  Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. , 1994, Optics letters.

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

[54]  Tobias Bonhoeffer,et al.  Homeostatic shutdown of long-term potentiation in the adult hippocampus. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[55]  Veronica Egger,et al.  Local Postsynaptic Voltage-Gated Sodium Channel Activation in Dendritic Spines of Olfactory Bulb Granule Cells , 2016, Neuron.

[56]  Stephan J Sigrist,et al.  Seeing the forest tree by tree: super-resolution light microscopy meets the neurosciences , 2013, Nature Neuroscience.

[57]  Rafael Yuste,et al.  Activity-dependent dendritic spine neck changes are correlated with synaptic strength , 2014, Proceedings of the National Academy of Sciences.

[58]  Bernardo L Sabatini,et al.  Anatomical and physiological plasticity of dendritic spines. , 2007, Annual review of neuroscience.

[59]  B. Sabatini,et al.  Glutamate induces de novo growth of functional spines in developing cortex , 2011, Nature.

[60]  Jun Noguchi,et al.  GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling , 2013, Nature Neuroscience.

[61]  U. Valentin Nägerl,et al.  Superresolution imaging for neuroscience , 2013, Experimental Neurology.

[62]  S. Raghavachari,et al.  Protein Crowding within the Postsynaptic Density Can Impede the Escape of Membrane Proteins , 2016, The Journal of Neuroscience.

[63]  Karen Zito,et al.  Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening , 2012, Proceedings of the National Academy of Sciences.

[64]  Bernardo L. Sabatini,et al.  Super-resolution 2-photon microscopy reveals that the morphology of each dendritic spine correlates with diffusive but not synaptic properties , 2014, Front. Neuroanat..

[65]  Stefan W. Hell,et al.  Supporting Online Material Materials and Methods Figs. S1 to S9 Tables S1 and S2 References Video-rate Far-field Optical Nanoscopy Dissects Synaptic Vesicle Movement , 2022 .

[66]  T. Svitkina,et al.  Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis , 2010, Molecular biology of the cell.

[67]  C. Wilson,et al.  Passive cable properties of dendritic spines and spiny neurons , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[68]  U. Nägerl,et al.  Spine neck plasticity regulates compartmentalization of synapses , 2014, Nature Neuroscience.

[69]  Daniel Choquet,et al.  Super-Resolution Imaging Reveals That AMPA Receptors Inside Synapses Are Dynamically Organized in Nanodomains Regulated by PSD95 , 2013, The Journal of Neuroscience.

[70]  U Valentin Nägerl,et al.  STED nanoscopy of actin dynamics in synapses deep inside living brain slices. , 2011, Biophysical journal.

[71]  Haruo Kasai,et al.  Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines , 2008, Science.

[72]  S.W. HELL,et al.  A compact STED microscope providing 3D nanoscale resolution , 2009, Journal of microscopy.

[73]  K. Svoboda,et al.  Structure and function of dendritic spines. , 2002, Annual review of physiology.

[74]  T. Kuner,et al.  Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition , 2016, Scientific Reports.

[75]  Rafael Yuste,et al.  Ultrastructure of Dendritic Spines: Correlation Between Synaptic and Spine Morphologies , 2007, Front. Neurosci..

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

[77]  Ryohei Yasuda,et al.  Biochemical Computation for Spine Structural Plasticity , 2015, Neuron.

[78]  M. Trommald,et al.  Dimensions and density of dendritic spines from rat dentate granule cells based on reconstructions from serial electron micrographs , 1997, The Journal of comparative neurology.

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