NMDA spikes enhance action potential generation during sensory input

Recent evidence in vitro suggests that the tuft dendrites of pyramidal neurons are capable of evoking local NMDA receptor–dependent electrogenesis, so-called NMDA spikes. However, it has so far proved difficult to demonstrate their existence in vivo. Moreover, it is not clear whether NMDA spikes are relevant to the output of pyramidal neurons. We found that local NMDA spikes occurred in tuft dendrites of layer 2/3 pyramidal neurons both spontaneously and following sensory input, and had a large influence on the number of output action potentials. Using two-photon activation of an intracellular caged NMDA receptor antagonist (tc-MK801), we found that isolated NMDA spikes typically occurred in multiple branches simultaneously and that sensory stimulation substantially increased their probability. Our results demonstrate that NMDA receptors have a vital role in coupling the tuft region of the layer 2/3 pyramidal neuron to the cell body, enhancing the effectiveness of layer 1 input.

[1]  R. E. Taylor.  Effect of procaine on electrical properties of squid axon membrane. , 1959, The American journal of physiology.

[2]  B. Connors,et al.  Electrophysiological properties of neocortical neurons in vitro. , 1982, Journal of neurophysiology.

[3]  B. Connors,et al.  Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons. , 1982, The Journal of pharmacology and experimental therapeutics.

[4]  D. Hubel.  Cortical neurobiology: a slanted historical perspective. , 1982, Annual review of neuroscience.

[5]  M. Mayer,et al.  Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones , 1984, Nature.

[6]  R. Andrade.  Blockade of neurotransmitter-activated K+ conductance by QX-314 in the rat hippocampus. , 1991, European journal of pharmacology.

[7]  D. J. Felleman,et al.  Distributed hierarchical processing in the primate cerebral cortex. , 1991, Cerebral cortex.

[8]  Bartlett W. Mel.  Synaptic integration in an excitable dendritic tree. , 1993, Journal of neurophysiology.

[9]  L. Cauller,et al.  Synaptic physiology of horizontal afferents to layer I in slices of rat SI neocortex , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  R K Wong,et al.  Intracellular QX-314 blocks the hyperpolarization-activated inward current Iq in hippocampal CA1 pyramidal cells. , 1995, Journal of neurophysiology.

[11]  Idan Segev,et al.  The morphoelectrotonic transform: a graphical approach to dendritic function , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  R. J. Sayer,et al.  Intracellular QX-314 inhibits calcium currents in hippocampal CA1 pyramidal neurons. , 1996, Journal of neurophysiology.

[13]  D. Kleinfeld,et al.  In vivo dendritic calcium dynamics in neocortical pyramidal neurons , 1997, Nature.

[14]  N. Spruston,et al.  Determinants of Voltage Attenuation in Neocortical Pyramidal Neuron Dendrites , 1998, The Journal of Neuroscience.

[15]  Winfried Denk,et al.  Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo , 1999, Nature Neuroscience.

[16]  Stephen R. Williams,et al.  Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons , 1999, The Journal of physiology.

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

[18]  Yitzhak Schiller,et al.  NMDA receptor-mediated dendritic spikes and coincident signal amplification , 2001, Current Opinion in Neurobiology.

[19]  G. Stuart,et al.  Dependence of EPSP Efficacy on Synapse Location in Neocortical Pyramidal Neurons , 2002, Science.

[20]  M. Larkum,et al.  Signaling of Layer 1 and Whisker-Evoked Ca2+ and Na+ Action Potentials in Distal and Terminal Dendrites of Rat Neocortical Pyramidal Neurons In Vitro and In Vivo , 2002, The Journal of Neuroscience.

[21]  Bert Sakmann,et al.  Supralinear Ca2+ Influx into Dendritic Tufts of Layer 2/3 Neocortical Pyramidal Neurons In Vitro and In Vivo , 2003, The Journal of Neuroscience.

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

[23]  Paul A. Rhodes,et al.  The Properties and Implications of NMDA Spikes in Neocortical Pyramidal Cells , 2006, The Journal of Neuroscience.

[24]  Urit Gordon,et al.  Plasticity Compartments in Basal Dendrites of Neocortical Pyramidal Neurons , 2006, The Journal of Neuroscience.

[25]  A. Polsky,et al.  Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study , 2007, Nature Neuroscience.

[26]  C. Gilbert,et al.  Brain States: Top-Down Influences in Sensory Processing , 2007, Neuron.

[27]  B. Sakmann,et al.  Dendritic Spikes in Apical Dendrites of Neocortical Layer 2/3 Pyramidal Neurons , 2007, The Journal of Neuroscience.

[28]  Matthew E Larkum,et al.  Synaptic clustering by dendritic signalling mechanisms , 2008, Current Opinion in Neurobiology.

[29]  Jackie Schiller,et al.  Spatiotemporally graded NMDA spike/plateau potentials in basal dendrites of neocortical pyramidal neurons. , 2008, Journal of neurophysiology.

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

[31]  M. Häusser,et al.  Dendritic Discrimination of Temporal Input Sequences in Cortical Neurons , 2010, Science.

[32]  Nathalie L Rochefort,et al.  Dendritic organization of sensory input to cortical neurons in vivo , 2010, Nature.

[33]  M. Larkum,et al.  Properties of Layer 6 Pyramidal Neuron Apical Dendrites , 2010, The Journal of Neuroscience.

[34]  Wen-Liang L Zhou,et al.  The decade of the dendritic NMDA spike , 2010, Journal of neuroscience research.

[35]  Joshua L. Plotkin,et al.  Synaptically driven state transitions in distal dendrites of striatal spiny neurons , 2011, Nature Neuroscience.

[36]  M. Häusser,et al.  Synaptic Integration Gradients in Single Cortical Pyramidal Cell Dendrites , 2011, Neuron.

[37]  Karl J. Friston,et al.  Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State , 2011, Science.

[38]  Nathalie L Rochefort,et al.  Functional mapping of single spines in cortical neurons in vivo , 2011, Nature.

[39]  Hazel A. Collins,et al.  Presynaptic Induction and Expression of Timing-Dependent Long-Term Depression Demonstrated by Compartment-Specific Photorelease of a Use-Dependent NMDA Receptor Antagonist , 2011, The Journal of Neuroscience.

[40]  Henry Markram,et al.  Models of Neocortical Layer 5b Pyramidal Cells Capturing a Wide Range of Dendritic and Perisomatic Active Properties , 2011, PLoS Comput. Biol..

[41]  M. Larkum,et al.  The Time Window for Generation of Dendritic Spikes by Coincidence of Action Potentials and EPSPs is Layer Specific in Somatosensory Cortex , 2012, PloS one.

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

[43]  Matthew W Self,et al.  Different glutamate receptors convey feedforward and recurrent processing in macaque V1 , 2012, Proceedings of the National Academy of Sciences.

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

[45]  O. Paulsen,et al.  Caged intracellular NMDA receptor blockers for the study of subcellular ion channel function , 2012, Communicative & integrative biology.

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

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

[48]  Daniel N Hill,et al.  Multibranch activity in basal and tuft dendrites during firing of layer 5 cortical neurons in vivo , 2013, Proceedings of the National Academy of Sciences.

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

[50]  M. Larkum.  A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex , 2013, Trends in Neurosciences.

[51]  Pieter R. Roelfsema,et al.  Distinct Roles of the Cortical Layers of Area V1 in Figure-Ground Segregation , 2013, Current Biology.

[52]  Nathalie L Rochefort,et al.  Reactivation of the same synapses during spontaneous up states and sensory stimuli. , 2013, Cell reports.