Activity-dependent PSD formation and stabilization of newly formed spines in hippocampal slice cultures.

Development and remodeling of synaptic networks occurs through a continuous turnover of dendritic spines. However, the mechanisms that regulate the formation and stabilization of newly formed spines remain poorly understood. Here, we applied repetitive confocal imaging to hippocampal slice cultures to address these issues. We find that, although the turnover rate of protrusions progressively decreased during development, the process of stabilization of new spines remained comparable both in terms of time course and low level of efficacy. Irrespective of the developmental stage, most new protrusions were quickly eliminated, in particular filopodia, which only occasionally lead to the formation of stable dendritic spines. We also found that the stabilization of new protrusions was determined within a critical period of 24 h and that this coincided with an enlargement of the spine head and the expression of tagged PSD-95. Blockade of postsynaptic AMPA and NMDA receptors significantly reduced the capacity of new spines to express tagged PSD-95 and decreased their probability to be stabilized. These results suggest a model in which synaptic development is associated with an extensive, nonspecific growth of protrusions followed by stabilization of a few of them through a mechanism that involves activity-driven formation of a postsynaptic density.

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

[2]  R. Nicoll,et al.  PSD-95 involvement in maturation of excitatory synapses. , 2000, Science.

[3]  O. Prange,et al.  Modular Transport of Postsynaptic Density-95 Clusters and Association with Stable Spine Precursors during Early Development of Cortical Neurons , 2001, The Journal of Neuroscience.

[4]  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.

[5]  Niraj S. Desai,et al.  Activity-dependent scaling of quantal amplitude in neocortical neurons , 1998, Nature.

[6]  Stephen J. Smith,et al.  Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation , 1996, Neuron.

[7]  Petter Laake,et al.  Different modes of expression of AMPA and NMDA receptors in hippocampal synapses , 1999, Nature Neuroscience.

[8]  Pascal Jourdain,et al.  Calcium/Calmodulin-Dependent Protein Kinase II Contributes to Activity-Dependent Filopodia Growth and Spine Formation , 2003, The Journal of Neuroscience.

[9]  W. Greenough,et al.  Hippocampal pyramidal cells in adult Fmr1 knockout mice exhibit an immature-appearing profile of dendritic spines , 2006, Brain Research.

[10]  J. Fiala,et al.  Synaptogenesis Via Dendritic Filopodia in Developing Hippocampal Area CA1 , 1998, The Journal of Neuroscience.

[11]  M. Segal.  Dendritic spines and long-term plasticity , 2005, Nature Reviews Neuroscience.

[12]  松崎 政紀.  Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons , 2001 .

[13]  Noam E. Ziv,et al.  Synapse development: still looking for the forest, still lost in the trees , 2006, Cell and Tissue Research.

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

[15]  H. Kasai,et al.  Structure–stability–function relationships of dendritic spines , 2003, Trends in Neurosciences.

[16]  S. Halpain,et al.  Dynamics and pathology of dendritic spines. , 2005, Progress in brain research.

[17]  R. Nicoll,et al.  Auxiliary Subunits Assist AMPA-Type Glutamate Receptors , 2006, Science.

[18]  Elena B. Pasquale,et al.  Molecular mechanisms of dendritic spine development and remodeling , 2005, Progress in Neurobiology.

[19]  Yi Zuo,et al.  Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex , 2005, Nature.

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

[21]  G. Shepherd,et al.  Transient and Persistent Dendritic Spines in the Neocortex In Vivo , 2005, Neuron.

[22]  Karel Svoboda,et al.  Rapid Redistribution of Synaptic PSD-95 in the Neocortex In Vivo , 2006, PLoS biology.

[23]  D. Chklovskii,et al.  Geometry and Structural Plasticity of Synaptic Connectivity , 2002, Neuron.

[24]  S. Nelson,et al.  Homeostatic plasticity in the developing nervous system , 2004, Nature Reviews Neuroscience.

[25]  D. Muller,et al.  Structural modifications associated with synaptic development in area CA1 of rat hippocampal organotypic cultures. , 1993, Brain research. Developmental brain research.

[26]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[27]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[28]  Marco Capogna,et al.  Miniature synaptic events maintain dendritic spines via AMPA receptor activation , 1999, Nature Neuroscience.

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

[30]  D. Debanne,et al.  Organotypic slice cultures: a technique has come of age , 1997, Trends in Neurosciences.

[31]  G. Marrs,et al.  Rapid formation and remodeling of postsynaptic densities in developing dendrites , 2001, Nature Neuroscience.

[32]  R. Nicoll,et al.  Expression mechanisms underlying long-term potentiation: a postsynaptic view. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[33]  N. Toni,et al.  Remodeling of Synaptic Membranes after Induction of Long-Term Potentiation , 2001, The Journal of Neuroscience.

[34]  H. Markram,et al.  Spontaneous and evoked synaptic rewiring in the neonatal neocortex , 2006, Proceedings of the National Academy of Sciences.

[35]  K. Svoboda,et al.  Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. , 1999, Science.

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

[37]  W. Gan,et al.  Development of Long-Term Dendritic Spine Stability in Diverse Regions of Cerebral Cortex , 2005, Neuron.

[38]  Rafael Yuste,et al.  Genesis of dendritic spines: insights from ultrastructural and imaging studies , 2004, Nature Reviews Neuroscience.

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

[40]  Peter Somogyi,et al.  Cell Type and Pathway Dependence of Synaptic AMPA Receptor Number and Variability in the Hippocampus , 1998, Neuron.

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

[42]  P. C. Murphy,et al.  Cerebral Cortex , 2017, Cerebral Cortex.

[43]  Tobias Bonhoeffer,et al.  Local calcium transients regulate the spontaneous motility of dendritic filopodia , 2005, Nature Neuroscience.

[44]  M. Ehlers,et al.  Organelles and trafficking machinery for postsynaptic plasticity. , 2006, Annual review of neuroscience.

[45]  R. Yuste,et al.  Non-synaptic dendritic spines in neocortex , 2007, Neuroscience.

[46]  Noam E. Ziv,et al.  The Dynamics of SAP90/PSD-95 Recruitment to New Synaptic Junctions , 2001, Molecular and Cellular Neuroscience.

[47]  J. R. Newton,et al.  Remodeling of Synaptic Structure in Sensory Cortical Areas In Vivo , 2006, The Journal of Neuroscience.

[48]  M. Segal,et al.  Dendritic spine density and LTP induction in cultured hippocampal slices. , 1997, Journal of neurophysiology.