Branch-specific dendritic Ca2+ spikes cause persistent synaptic plasticity

The brain has an extraordinary capacity for memory storage, but how it stores new information without disrupting previously acquired memories remains unknown. Here we show that different motor learning tasks induce dendritic Ca2+ spikes on different apical tuft branches of individual layer V pyramidal neurons in the mouse motor cortex. These task-related, branch-specific Ca2+ spikes cause long-lasting potentiation of postsynaptic dendritic spines active at the time of spike generation. When somatostatin-expressing interneurons are inactivated, different motor tasks frequently induce Ca2+ spikes on the same branches. On those branches, spines potentiated during one task are depotentiated when they are active seconds before Ca2+ spikes induced by another task. Concomitantly, increased neuronal activity and performance improvement after learning one task are disrupted when another task is learned. These findings indicate that dendritic-branch-specific generation of Ca2+ spikes is crucial for establishing long-lasting synaptic plasticity, thereby facilitating information storage associated with different learning experiences.

[1]  W. N. Ross,et al.  Mapping calcium transients in the dendrites of Purkinje cells from the guinea‐pig cerebellum in vitro. , 1987, The Journal of physiology.

[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]  W. N. Ross,et al.  The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurons , 1992, Nature.

[4]  M. Ahissar,et al.  Dependence of cortical plasticity on correlated activity of single neurons and on behavioral context. , 1992, Science.

[5]  Rafael Yuste,et al.  Ca2+ accumulations in dendrites of neocortical pyramidal neurons: An apical band and evidence for two functional compartments , 1994, Neuron.

[6]  B. Sakmann,et al.  Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons , 1997, The Journal of physiology.

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

[8]  S. J. Martin,et al.  Synaptic plasticity and memory: an evaluation of the hypothesis. , 2000, Annual review of neuroscience.

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

[10]  H. Yonekawa,et al.  Diphtheria toxin receptor–mediated conditional and targeted cell ablation in transgenic mice , 2001, Nature Biotechnology.

[11]  P. J. Sjöström,et al.  Spike timing, calcium signals and synaptic plasticity , 2002, Current Opinion in Neurobiology.

[12]  Nace L. Golding,et al.  Dendritic spikes as a mechanism for cooperative long-term potentiation , 2002, Nature.

[13]  P. Detwiler,et al.  Directionally selective calcium signals in dendrites of starburst amacrine cells , 2002, Nature.

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

[15]  K. Holthoff,et al.  Single‐shock LTD by local dendritic spikes in pyramidal neurons of mouse visual cortex , 2004, The Journal of physiology.

[16]  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.

[17]  Andreas R Luft,et al.  Short and long-term motor skill learning in an accelerated rotarod training paradigm , 2004, Neurobiology of Learning and Memory.

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

[19]  W. Abraham,et al.  Memory retention – the synaptic stability versus plasticity dilemma , 2005, Trends in Neurosciences.

[20]  N. Spruston,et al.  Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing-dependent plasticity , 2005, Nature Neuroscience.

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

[22]  Y. Humeau,et al.  Dendritic calcium spikes induce bi-directional synaptic plasticity in the lateral amygdala , 2007, Neuropharmacology.

[23]  N. Spruston,et al.  Dendritic spikes induce single-burst long-term potentiation , 2007, Proceedings of the National Academy of Sciences.

[24]  B. Roth,et al.  Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand , 2007, Proceedings of the National Academy of Sciences.

[25]  Judit K. Makara,et al.  Compartmentalized dendritic plasticity and input feature storage in neurons , 2008, Nature.

[26]  Guilherme Neves,et al.  Synaptic plasticity, memory and the hippocampus: a neural network approach to causality , 2008, Nature Reviews Neuroscience.

[27]  N. Spruston.  Pyramidal neurons: dendritic structure and synaptic integration , 2008, Nature Reviews Neuroscience.

[28]  A. Polsky,et al.  Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle , 2009, Science.

[29]  W. Senn,et al.  Dendritic encoding of sensory stimuli controlled by deep cortical interneurons , 2009, Nature.

[30]  J. Kleim,et al.  The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture. , 2011, Cerebral cortex.

[31]  Susumu Tonegawa,et al.  The Dendritic Branch Is the Preferred Integrative Unit for Protein Synthesis-Dependent LTP , 2011, Neuron.

[32]  Jochen F Staiger,et al.  Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex , 2012, Nature Neuroscience.

[33]  Mark T. Harnett,et al.  Nonlinear dendritic integration of sensory and motor input during an active sensing task , 2012, Nature.

[34]  Benjamin R. Arenkiel,et al.  Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice , 2012, Neuron.

[35]  Jackie Schiller,et al.  Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo , 2012, Nature.

[36]  Spencer L. Smith,et al.  Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo , 2013, Nature.

[37]  J. Schiller,et al.  Active properties of neocortical pyramidal neuron dendrites. , 2013, Annual review of neuroscience.

[38]  W. Gan,et al.  Transcranial two-photon imaging of synaptic structures in the cortex of awake head-restrained mice. , 2013, Methods in molecular biology.

[39]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[40]  Xiaolong Jiang,et al.  The organization of two new cortical interneuronal circuits , 2013, Nature Neuroscience.

[41]  G. Fishell,et al.  A disinhibitory circuit mediates motor integration in the somatosensory cortex , 2013, Nature Neuroscience.

[42]  Thomas M. Morse,et al.  Compartmentalization of GABAergic Inhibition by Dendritic Spines , 2013, Science.

[43]  Mark T. Harnett,et al.  An optimized fluorescent probe for visualizing glutamate neurotransmission , 2013, Nature Methods.

[44]  Mark T. Harnett,et al.  Potassium Channels Control the Interaction between Active Dendritic Integration Compartments in Layer 5 Cortical Pyramidal Neurons , 2013, Neuron.

[45]  W. Gan,et al.  Sleep promotes branch-specific formation of dendritic spines after learning , 2014, Science.

[46]  Christine Grienberger,et al.  NMDA Receptor-Dependent Multidendrite Ca2+ Spikes Required for Hippocampal Burst Firing In Vivo , 2014, Neuron.

[47]  M. Larkum,et al.  NMDA spikes enhance action potential generation during sensory input , 2014, Nature Neuroscience.