A model of activity-dependent changes in dendritic spine density and spine structure

Recent evidence indicates that the morphology and density of dendritic spines are regulated during synaptic plasticity. See, for instance, a review by Hayashi and Majewska [9]. In this work, we extend previous modeling studies [27] by combining a model for activity-dependent spine density with one for calcium-mediated spine stem restructuring. The model is based on the standard dimensionless cable equation, which represents the change in the membrane potential in a passive dendrite. Additional equations characterize the change in spine density along the dendrite, the current balance equation for an individual spine head, the change in calcium concentration in the spine head, and the dynamics of spine stem resistance. We use computational studies to investigate the changes in spine density and structure for differing synaptic inputs and demonstrate the effects of these changes on the input-output properties of the dendritic branch. Moderate amounts of high-frequency synaptic activation to dendritic spines result in an increase in spine stem resistance that is correlated with spine stem elongation. In addition, the spine density increases both inside and outside the input region. The model is formulated so that this long-term potentiation-inducing stimulus eventually leads to structural stability. In contrast, a prolonged low-frequency stimulation paradigm that would typically induce long-term depression results in a decrease in stem resistance (correlated with stem shortening) and an eventual decrease in spine density.

[1]  Yasunori Hayashi,et al.  Dendritic Spine Geometry: Functional Implication and Regulation , 2005, Neuron.

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

[3]  S. Baer,et al.  Asymptotic analysis of noise sensitivity in a neuronal burster , 2002, Bulletin of mathematical biology.

[4]  R. Yuste,et al.  Mechanisms of Calcium Decay Kinetics in Hippocampal Spines: Role of Spine Calcium Pumps and Calcium Diffusion through the Spine Neck in Biochemical Compartmentalization , 2000, The Journal of Neuroscience.

[5]  M. Sheng,et al.  Dentritic spines : structure, dynamics and regulation , 2001, Nature Reviews Neuroscience.

[6]  R. Yuste,et al.  Morphological changes in dendritic spines associated with long-term synaptic plasticity. , 2001, Annual review of neuroscience.

[7]  M. Segal,et al.  Fast confocal imaging of calcium released from stores in dendritic spines , 1998, The European journal of neuroscience.

[8]  Eduard Korkotian,et al.  Dendritic spine formation and pruning: common cellular mechanisms? , 2000, Trends in Neurosciences.

[9]  S. Baer,et al.  Analysis of an excitable dendritic spine with an activity-dependent stem conductance , 1998, Journal of mathematical biology.

[10]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[11]  Rafael Yuste,et al.  Calcium Dynamics of Spines Depend on Their Dendritic Location , 2002, Neuron.

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

[13]  J Rinzel,et al.  Propagation of dendritic spikes mediated by excitable spines: a continuum theory. , 1991, Journal of neurophysiology.

[14]  B H Gähwiler,et al.  Reversible loss of dendritic spines and altered excitability after chronic epilepsy in hippocampal slice cultures. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Barbara Calabrese,et al.  Development and regulation of dendritic spine synapses. , 2006, Physiology.

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

[17]  T. H. Brown,et al.  Confocal laser scanning microscopy reveals voltage-gated calcium signals within hippocampal dendritic spines. , 1994, Journal of neurobiology.

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

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

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

[21]  K. Harris Calcium from internal stores modifies dendritic spine shape. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

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

[23]  Joseph E LeDoux,et al.  Structural plasticity and memory , 2004, Nature Reviews Neuroscience.

[24]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[25]  D Holcman,et al.  Calcium dynamics in dendritic spines and spine motility. , 2004, Biophysical journal.

[26]  S. Baer,et al.  Impact of time-dependent changes in spine density and spine shape on the input-output properties of a dendritic branch: a computational study. , 2005, Journal of neurophysiology.