Membrane Potential Dynamics of Neocortical Projection Neurons Driving Target-Specific Signals

Primary sensory cortex discriminates incoming sensory information and generates multiple processing streams toward other cortical areas. However, the underlying cellular mechanisms remain unknown. Here, by making whole-cell recordings in primary somatosensory barrel cortex (S1) of behaving mice, we show that S1 neurons projecting to primary motor cortex (M1) and those projecting to secondary somatosensory cortex (S2) have distinct intrinsic membrane properties and exhibit markedly different membrane potential dynamics during behavior. Passive tactile stimulation evoked faster and larger postsynaptic potentials (PSPs) in M1-projecting neurons, rapidly driving phasic action potential firing, well-suited for stimulus detection. Repetitive active touch evoked strongly depressing PSPs and only transient firing in M1-projecting neurons. In contrast, PSP summation allowed S2-projecting neurons to robustly signal sensory information accumulated during repetitive touch, useful for encoding object features. Thus, target-specific transformation of sensory-evoked synaptic potentials by S1 projection neurons generates functionally distinct output signals for sensorimotor coordination and sensory perception.

[1]  D. Kleinfeld,et al.  'Where' and 'what' in the whisker sensorimotor system , 2008, Nature Reviews Neuroscience.

[2]  Yasuo Kawaguchi,et al.  Cell Diversity and Connection Specificity between Callosal Projection Neurons in the Frontal Cortex , 2011, The Journal of Neuroscience.

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

[4]  Lin Tian,et al.  Activity in motor-sensory projections reveals distributed coding in somatosensation , 2012, Nature.

[5]  Winfried Denk,et al.  Targeted Whole-Cell Recordings in the Mammalian Brain In Vivo , 2003, Neuron.

[6]  Atsushi Miyawaki,et al.  Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain , 2011, Nature Neuroscience.

[7]  W. Denk,et al.  Targeted patch-clamp recordings and single-cell electroporation of unlabeled neurons in vivo , 2008, Nature Methods.

[8]  R. Spreafico,et al.  SII-projecting neurons in the rat thalamus: a single- and double-retrograde-tracing study. , 1987, Somatosensory research.

[9]  C. Petersen,et al.  Long‐range connectivity of mouse primary somatosensory barrel cortex , 2010, The European journal of neuroscience.

[10]  C. Cepko,et al.  Electroporation and RNA interference in the rodent retina in vivo and in vitro , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Sherman,et al.  Synaptic properties of thalamic and intracortical inputs to layer 4 of the first- and higher-order cortical areas in the auditory and somatosensory systems. , 2008, Journal of neurophysiology.

[12]  K. Deisseroth,et al.  In Vivo Optogenetic Stimulation of Neocortical Excitatory Neurons Drives Brain-State-Dependent Inhibition , 2011, Current Biology.

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

[14]  R. Wurtz,et al.  Comparison of cortico-cortical and cortico-collicular signals for the generation of saccadic eye movements. , 2002, Journal of neurophysiology.

[15]  A. Grinvald,et al.  Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Karel Svoboda,et al.  Long-Range Neuronal Circuits Underlying the Interaction between Sensory and Motor Cortex , 2011, Neuron.

[17]  Emery N. Brown,et al.  Functional Biases in Visual Cortex Neurons with Identified Projections to Higher Cortical Targets , 2012, Current Biology.

[18]  Fritjof Helmchen,et al.  HelioScan: A software framework for controlling in vivo microscopy setups with high hardware flexibility, functional diversity and extendibility , 2013, Journal of Neuroscience Methods.

[19]  J. Poulet,et al.  Thalamic control of cortical states , 2012, Nature Neuroscience.

[20]  Anthony J. Movshon,et al.  Visual Response Properties of Striate Cortical Neurons Projecting to Area MT in Macaque Monkeys , 1996, The Journal of Neuroscience.

[21]  D. Simons,et al.  Thalamic and corticocortical connections of the second somatic sensory area of the mouse , 1987, The Journal of comparative neurology.

[22]  N. Tamamaki,et al.  Long-Range GABAergic Connections Distributed throughout the Neocortex and their Possible Function , 2010, Front. Neurosci..

[23]  A. E. Casale,et al.  Motor Cortex Feedback Influences Sensory Processing by Modulating Network State , 2013, Neuron.

[24]  R. Turner,et al.  Corticostriatal Activity in Primary Motor Cortex of the Macaque , 2000, The Journal of Neuroscience.

[25]  M. Goodale,et al.  Separate visual pathways for perception and action , 1992, Trends in Neurosciences.

[26]  Lindsey L. Glickfeld,et al.  Cortico-cortical projections in mouse visual cortex are functionally target specific , 2013, Nature Neuroscience.

[27]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[28]  Y. Kubota,et al.  Highly Differentiated Projection-Specific Cortical Subnetworks , 2011, The Journal of Neuroscience.

[29]  C. Petersen,et al.  Membrane potential correlates of sensory perception in mouse barrel cortex , 2013, Nature Neuroscience.

[30]  E. Callaway,et al.  Parallel processing strategies of the primate visual system , 2009, Nature Reviews Neuroscience.

[31]  J. Rauschecker,et al.  Mechanisms and streams for processing of "what" and "where" in auditory cortex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Hestrin,et al.  Intracortical circuits of pyramidal neurons reflect their long-range axonal targets , 2009, Nature.

[33]  C. Gray,et al.  Dynamic spike threshold reveals a mechanism for synaptic coincidence detection in cortical neurons in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Allan R. Jones,et al.  A robust and high-throughput Cre reporting and characterization system for the whole mouse brain , 2009, Nature Neuroscience.

[35]  M. Larkum,et al.  The Cellular Basis of GABAB-Mediated Interhemispheric Inhibition , 2012, Science.

[36]  C. Petersen,et al.  Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Behaving Mice , 2010, Neuron.

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

[38]  H. Markram,et al.  Morphological, Electrophysiological, and Synaptic Properties of Corticocallosal Pyramidal Cells in the Neonatal Rat Neocortex , 2006 .

[39]  F. Helmchen,et al.  Barrel cortex function , 2013, Progress in Neurobiology.

[40]  M. Häusser,et al.  The single dendritic branch as a fundamental functional unit in the nervous system , 2010, Current Opinion in Neurobiology.

[41]  F Bremmer,et al.  Directional asymmetry of neurons in cortical areas MT and MST projecting to the NOT-DTN in macaques. , 2002, Journal of neurophysiology.

[42]  C. Petersen The Functional Organization of the Barrel Cortex , 2007, Neuron.

[43]  F. Helmchen,et al.  Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex , 2013, Nature.

[44]  Michael Okun,et al.  The Subthreshold Relation between Cortical Local Field Potential and Neuronal Firing Unveiled by Intracellular Recordings in Awake Rats , 2010, The Journal of Neuroscience.

[45]  C. Petersen,et al.  Correlating whisker behavior with membrane potential in barrel cortex of awake mice , 2006, Nature Neuroscience.

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

[47]  D. Kleinfeld,et al.  Phase-to-rate transformations encode touch in cortical neurons of a scanning sensorimotor system , 2009, Nature Neuroscience.

[48]  F. Haiss,et al.  Spatiotemporal Dynamics of Cortical Sensorimotor Integration in Behaving Mice , 2007, Neuron.

[49]  T. Kaneko,et al.  Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67‐GFP knock‐in mouse , 2003, The Journal of comparative neurology.

[50]  Celine Mateo,et al.  Motor Control by Sensory Cortex , 2010, Science.

[51]  J. Poulet,et al.  Synaptic Mechanisms Underlying Sparse Coding of Active Touch , 2011, Neuron.

[52]  M. Häusser,et al.  Targeted single-cell electroporation of mammalian neurons in vivo , 2009, Nature Protocols.

[53]  Sylvain Crochet,et al.  Synaptic Computation and Sensory Processing in Neocortical Layer 2/3 , 2013, Neuron.

[54]  Ian R. Wickersham,et al.  Hierarchical Connectivity and Connection-Specific Dynamics in the Corticospinal–Corticostriatal Microcircuit in Mouse Motor Cortex , 2012, The Journal of Neuroscience.

[55]  R. Reep,et al.  Multiple neuroanatomical tract-tracing using fluorescent Alexa Fluor conjugates of cholera toxin subunit B in rats , 2009, Nature Protocols.

[56]  J. Poulet,et al.  Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice , 2008, Nature.

[57]  E. Welker,et al.  Organization of feedback and feedforward projections of the barrel cortex: a PHA-L study in the mouse , 2004, Experimental Brain Research.

[58]  S. Nelson,et al.  A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex , 2011, Neuron.

[59]  Y. Kawaguchi,et al.  Recurrent Connection Patterns of Corticostriatal Pyramidal Cells in Frontal Cortex , 2006, The Journal of Neuroscience.

[60]  Daniel N. Hill,et al.  Primary Motor Cortex Reports Efferent Control of Vibrissa Motion on Multiple Timescales , 2011, Neuron.

[61]  Karel Svoboda,et al.  The Functional Properties of Barrel Cortex Neurons Projecting to the Primary Motor Cortex , 2010, The Journal of Neuroscience.

[62]  Y. Dan,et al.  Neuromodulation of Brain States , 2012, Neuron.