Sublinear integration underlies binocular processing in primary visual cortex

Although we know much about the capacity of neurons to integrate synaptic inputs in vitro, less is known about synaptic integration in vivo. Here we address this issue by investigating the integration of inputs from the two eyes in mouse primary visual cortex. We find that binocular inputs to layer 2/3 pyramidal neurons are integrated sublinearly in an amplitude-dependent manner. Sublinear integration was greatest when binocular responses were largest, as occurs at the preferred orientation and binocular disparity, and highest contrast. Using voltage-clamp experiments and modeling, we show that sublinear integration occurs postsynaptically. The extent of sublinear integration cannot be accounted for solely by nonlinear integration of excitatory inputs, even when they are activated closely in space and time, but requires balanced recruitment of inhibition. Finally, we show that sublinear binocular integration acts as a divisive form of gain control, linearizing the output of binocular neurons and enhancing orientation selectivity.

[1]  Tobias Bonhoeffer,et al.  Activity-Dependent Clustering of Functional Synaptic Inputs on Developing Hippocampal Dendrites , 2011, Neuron.

[2]  Nicholas J. Priebe,et al.  Orientation Selectivity of Synaptic Input to Neurons in Mouse and Cat Primary Visual Cortex , 2011, The Journal of Neuroscience.

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

[4]  R. Yuste,et al.  Input Summation by Cultured Pyramidal Neurons Is Linear and Position-Independent , 1998, The Journal of Neuroscience.

[5]  Bert Sakmann,et al.  Dendritic coding of multiple sensory inputs in single cortical neurons in vivo , 2011, Proceedings of the National Academy of Sciences.

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

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

[8]  W. M. Keck,et al.  Highly Selective Receptive Fields in Mouse Visual Cortex , 2008, The Journal of Neuroscience.

[9]  Simon J. Mitchell,et al.  Direct measurement of somatic voltage clamp errors in central neurons , 2008, Nature Neuroscience.

[10]  Nicholas J. Priebe,et al.  The contribution of spike threshold to the dichotomy of cortical simple and complex cells , 2004, Nature Neuroscience.

[11]  D. McCormick,et al.  Rapid Neocortical Dynamics: Cellular and Network Mechanisms , 2009, Neuron.

[12]  B. Sakmann,et al.  A new cellular mechanism for coupling inputs arriving at different cortical layers , 1999, Nature.

[13]  Jeffrey C. Magee,et al.  Dendritic Ih normalizes temporal summation in hippocampal CA1 neurons , 1999, Nature Neuroscience.

[14]  W. Guido,et al.  Loss of binocular responses and reduced retinal convergence during the period of retinogeniculate axon segregation. , 2006, Journal of neurophysiology.

[15]  H. Miyakawa,et al.  Optical monitoring of synaptic summation along the dendrites of CA1 pyramidal neurons , 2002, Neuroscience.

[16]  B. Sakmann,et al.  Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons , 1995, Neuron.

[17]  M. Carandini,et al.  Membrane Potential and Firing Rate in Cat Primary Visual Cortex , 2000, The Journal of Neuroscience.

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

[19]  R. Yuste,et al.  Linear Summation of Excitatory Inputs by CA1 Pyramidal Neurons , 1999, Neuron.

[20]  I. Ohzawa,et al.  The binocular organization of complex cells in the cat's visual cortex. , 1986, Journal of neurophysiology.

[21]  D. Ferster,et al.  Direction selectivity of synaptic potentials in simple cells of the cat visual cortex. , 1997, Journal of neurophysiology.

[22]  D. Johnston,et al.  Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. , 1995, Science.

[23]  S. Cruikshank,et al.  Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex , 2007, Nature Neuroscience.

[24]  M. Carandini,et al.  Parvalbumin-Expressing Interneurons Linearly Transform Cortical Responses to Visual Stimuli , 2012, Neuron.

[25]  Jianhua Cang,et al.  Critical Period Plasticity Matches Binocular Orientation Preference in the Visual Cortex , 2010, Neuron.

[26]  Nathan R. Wilson,et al.  Division and subtraction by distinct cortical inhibitory networks in vivo , 2012, Nature.

[27]  B. Sakmann,et al.  Action potential initiation and propagation in rat neocortical pyramidal neurons , 1997, The Journal of physiology.

[28]  Hongbo Jia,et al.  Dendritic organization of sensory input to cortical neurons in vivo , 2010, Nature.

[29]  D. Johnston,et al.  K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons , 1997, Nature.

[30]  I. Ohzawa,et al.  The binocular organization of simple cells in the cat's visual cortex. , 1986, Journal of neurophysiology.

[31]  A. B. Bonds,et al.  Classifying simple and complex cells on the basis of response modulation , 1991, Vision Research.

[32]  I. Ohzawa,et al.  Stereoscopic depth discrimination in the visual cortex: neurons ideally suited as disparity detectors. , 1990, Science.

[33]  J. Magee,et al.  Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons , 2006, Neuron.

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

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

[36]  I. Ohzawa,et al.  Neural mechanisms for encoding binocular disparity: receptive field position versus phase. , 1999, Journal of neurophysiology.

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

[38]  Norio Matsuki,et al.  Locally Synchronized Synaptic Inputs , 2012, Science.

[39]  Roland Krueppel,et al.  Dendritic Integration in Hippocampal Dentate Granule Cells , 2011, Neuron.

[40]  Gregory C. DeAngelis,et al.  Depth is encoded in the visual cortex by a specialized receptive field structure , 1991, Nature.

[41]  W. Guido,et al.  Structural and functional composition of the developing retinogeniculate pathway in the mouse , 2005, Visual Neuroscience.

[42]  M. Feller,et al.  Retinogeniculate Axons Undergo Eye-Specific Segregation in the Absence of Eye-Specific Layers , 2002, The Journal of Neuroscience.

[43]  B. Sakmann,et al.  In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain , 2002, Pflügers Archiv.

[44]  P. Medini.  Layer- and Cell-Type-Specific Subthreshold and Suprathreshold Effects of Long-Term Monocular Deprivation in Rat Visual Cortex , 2011, The Journal of Neuroscience.

[45]  R. Shapley,et al.  Orientation Selectivity in Macaque V1: Diversity and Laminar Dependence , 2002, The Journal of Neuroscience.

[46]  R. Silver,et al.  High-Probability Uniquantal Transmission at Excitatory Synapses in Barrel Cortex , 2003, Science.

[47]  Lief E. Fenno,et al.  Neocortical excitation/inhibition balance in information processing and social dysfunction , 2011, Nature.

[48]  G. Stuart,et al.  Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model , 2007, The Journal of physiology.

[49]  Karl Deisseroth,et al.  Activation of Specific Interneurons Improves V1 Feature Selectivity and Visual Perception , 2012, Nature.

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

[51]  Y. Frégnac,et al.  Visual input evokes transient and strong shunting inhibition in visual cortical neurons , 1998, Nature.

[52]  L. Maffei,et al.  Functional Masking of Deprived Eye Responses by Callosal Input during Ocular Dominance Plasticity , 2009, Neuron.

[53]  T. Poggio,et al.  Nonlinear interactions in a dendritic tree: localization, timing, and role in information processing. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

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

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