Learning Enhances Sensory Processing in Mouse V1 before Improving Behavior

A fundamental property of visual cortex is to enhance the representation of those stimuli that are relevant for behavior, but it remains poorly understood how such enhanced representations arise during learning. Using classical conditioning in adult mice of either sex, we show that orientation discrimination is learned in a sequence of distinct behavioral stages, in which animals first rely on stimulus appearance before exploiting its orientation to guide behavior. After confirming that orientation discrimination under classical conditioning requires primary visual cortex (V1), we measured, during learning, response properties of V1 neurons. Learning improved neural discriminability, sharpened orientation tuning, and led to higher contrast sensitivity. Remarkably, these learning-related improvements in the V1 representation were fully expressed before successful orientation discrimination was evident in the animals' behavior. We propose that V1 plays a key role early in discrimination learning to enhance behaviorally relevant sensory information. SIGNIFICANCE STATEMENT Decades of research have documented that responses of neurons in visual cortex can reflect the behavioral relevance of visual information. The behavioral relevance of any stimulus needs to be learned, though, and little is known how visual sensory processing changes, as the significance of a stimulus becomes clear. Here, we trained mice to discriminate two visual stimuli, precisely quantified when learning happened, and measured, during learning, the neural representation of these stimuli in V1. We observed learning-related improvements in V1 processing, which were fully expressed before discrimination was evident in the animals' behavior. These findings indicate that sensory and behavioral improvements can follow different time courses and point toward a key role of V1 at early stages in discrimination learning.

[1]  Haishan Yao,et al.  Contrast-dependent orientation discrimination in the mouse , 2015, Scientific Reports.

[2]  M. Bear,et al.  Instructive Effect of Visual Experience in Mouse Visual Cortex , 2006, Neuron.

[3]  T. Poggio,et al.  Fast perceptual learning in hyperacuity , 1995, Vision Research.

[4]  M. Stryker,et al.  Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion , 2014, Neuron.

[5]  C. Gilbert,et al.  Adult Visual Cortical Plasticity , 2012, Neuron.

[6]  J. S Stahl,et al.  A comparison of video and magnetic search coil recordings of mouse eye movements , 2000, Journal of Neuroscience Methods.

[7]  J. Gottlieb Attention, Learning, and the Value of Information , 2012, Neuron.

[8]  N. Mackintosh A Theory of Attention: Variations in the Associability of Stimuli with Reinforcement , 1975 .

[9]  C. Gilbert,et al.  Learning to Link Visual Contours , 2008, Neuron.

[10]  Frank Tong,et al.  Perceptual Learning Selectively Refines Orientation Representations in Early Visual Cortex , 2012, The Journal of Neuroscience.

[11]  C. Gilbert,et al.  Learning to see: experience and attention in primary visual cortex , 2001, Nature Neuroscience.

[12]  N. Logothetis,et al.  In Vivo Measurement of Cortical Impedance Spectrum in Monkeys: Implications for Signal Propagation , 2007, Neuron.

[13]  Na Ji,et al.  Thalamus provides layer 4 of primary visual cortex with orientation- and direction-tuned inputs , 2015, Nature Neuroscience.

[14]  J. Pearce,et al.  Theories of associative learning in animals. , 2001, Annual review of psychology.

[15]  Lynn Hazan,et al.  Klusters, NeuroScope, NDManager: A free software suite for neurophysiological data processing and visualization , 2006, Journal of Neuroscience Methods.

[16]  C. Gallistel,et al.  Time, rate, and conditioning. , 2000, Psychological review.

[17]  Harvey A Swadlow,et al.  Task difficulty modulates the activity of specific neuronal populations in primary visual cortex , 2008, Nature Neuroscience.

[18]  Louise S. Delicato,et al.  Acetylcholine contributes through muscarinic receptors to attentional modulation in V1 , 2008, Nature.

[19]  J. Edeline,et al.  Rapid development of learning-induced receptive field plasticity in the auditory cortex. , 1993, Behavioral neuroscience.

[20]  S. Hestrin,et al.  Subthreshold Mechanisms Underlying State-Dependent Modulation of Visual Responses , 2013, Neuron.

[21]  J. Gallant,et al.  Attention to Stimulus Features Shifts Spectral Tuning of V4 Neurons during Natural Vision , 2008, Neuron.

[22]  Y. Dan,et al.  Spike timing-dependent plasticity: a Hebbian learning rule. , 2008, Annual review of neuroscience.

[23]  Yuka Sasaki,et al.  Different Dynamics of Performance and Brain Activation in the Time Course of Perceptual Learning , 2008, Neuron.

[24]  C. Schroeder,et al.  A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque. , 1998, Cerebral cortex.

[25]  C. Gilbert,et al.  Interactions between attention, context and learning in primary visual cortex , 2000, Vision Research.

[26]  S. McKee,et al.  Improvement in vernier acuity with practice , 1978, Perception & psychophysics.

[27]  M. Fee Oculomotor learning revisited: a model of reinforcement learning in the basal ganglia incorporating an efference copy of motor actions , 2012, Front. Neural Circuits.

[28]  Cyriel M A Pennartz,et al.  In Vivo Two-Photon Ca2+ Imaging Reveals Selective Reward Effects on Stimulus-Specific Assemblies in Mouse Visual Cortex , 2013, The Journal of Neuroscience.

[29]  Peter De Weerd,et al.  Introduction to Plasticity in the Visual System: From Genes to Circuits , 2006 .

[30]  Pieter R Roelfsema,et al.  Separable Codes for Attention and Luminance Contrast in the Primary Visual Cortex , 2010, The Journal of Neuroscience.

[31]  Akihiro Funamizu,et al.  Progressive plasticity of auditory cortex during appetitive operant conditioning , 2010, Biosyst..

[32]  N. Weinberger Specific long-term memory traces in primary auditory cortex , 2004, Nature Reviews Neuroscience.

[33]  David S. Greenberg,et al.  Rats maintain an overhead binocular field at the expense of constant fusion , 2013, Nature.

[34]  D. G. Albrecht,et al.  Striate cortex of monkey and cat: contrast response function. , 1982, Journal of neurophysiology.

[35]  C. Gallistel,et al.  Temporal maps and informativeness in associative learning , 2009, Trends in Neurosciences.

[36]  P. Golshani,et al.  Cellular mechanisms of brain-state-dependent gain modulation in visual cortex , 2013, Nature Neuroscience.

[37]  Tobias Bonhoeffer,et al.  Altered Visual Experience Induces Instructive Changes of Orientation Preference in Mouse Visual Cortex , 2011, The Journal of Neuroscience.

[38]  M. Stryker,et al.  Modulation of Visual Responses by Behavioral State in Mouse Visual Cortex , 2010, Neuron.

[39]  Quanxin Wang,et al.  Gateways of Ventral and Dorsal Streams in Mouse Visual Cortex , 2011, The Journal of Neuroscience.

[40]  C. Gallistel,et al.  The learning curve: implications of a quantitative analysis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Michael J. Goard,et al.  Fast Modulation of Visual Perception by Basal Forebrain Cholinergic Neurons , 2013, Nature Neuroscience.

[42]  M. Bear,et al.  A Cholinergic Mechanism for Reward Timing within Primary Visual Cortex , 2013, Neuron.

[43]  C. Cavada,et al.  Dopamine Innervation in the Thalamus: Monkey versus Rat , 2008, Cerebral cortex.

[44]  J. Pearce,et al.  A model for Pavlovian learning: variations in the effectiveness of conditioned but not of unconditioned stimuli. , 1980, Psychological review.

[45]  Lindsey L. Glickfeld,et al.  Mouse Primary Visual Cortex Is Used to Detect Both Orientation and Contrast Changes , 2013, The Journal of Neuroscience.

[46]  C. Gallistel,et al.  The rat approximates an ideal detector of changes in rates of reward: implications for the law of effect. , 2001, Journal of experimental psychology. Animal behavior processes.

[47]  Tadashi Isa,et al.  Quantitative analysis of spontaneous saccade-like rapid eye movements in C57BL/6 mice , 2007, Neuroscience Research.

[48]  Edi Barkai,et al.  A cellular correlate of learning-induced metaplasticity in the hippocampus. , 2006, Cerebral cortex.

[49]  Michael M Merzenich,et al.  Perceptual Learning Directs Auditory Cortical Map Reorganization through Top-Down Influences , 2006, The Journal of Neuroscience.

[50]  R. Reid,et al.  Frontiers in Cellular Neuroscience Cellular Neuroscience Methods Article , 2022 .

[51]  C. Furmanski,et al.  Learning Strengthens the Response of Primary Visual Cortex to Simple Patterns , 2004, Current Biology.

[52]  C. Gallistel,et al.  Autoshaped head poking in the mouse: a quantitative analysis of the learning curve. , 2006, Journal of the experimental analysis of behavior.

[53]  M. Stryker,et al.  A Cortical Circuit for Gain Control by Behavioral State , 2014, Cell.

[54]  Georg B. Keller,et al.  Learning Enhances Sensory and Multiple Non-sensory Representations in Primary Visual Cortex , 2015, Neuron.

[55]  John H. R. Maunsell,et al.  Neuronal Mechanisms of Visual Attention. , 2015, Annual review of vision science.

[56]  Jonathan W. Pillow,et al.  Single-trial spike trains in parietal cortex reveal discrete steps during decision-making , 2015, Science.

[57]  Michael P. Kilgard,et al.  Cortical Map Plasticity Improves Learning but Is Not Necessary for Improved Performance , 2011, Neuron.

[58]  G. Orban,et al.  Learning to See the Difference Specifically Alters the Most Informative V4 Neurons , 2006, The Journal of Neuroscience.

[59]  C. Nicholson,et al.  Theory of current source-density analysis and determination of conductivity tensor for anuran cerebellum. , 1975, Journal of neurophysiology.

[60]  R. Huerta,et al.  A Computational Framework for Understanding Decision Making through Integration of Basic Learning Rules , 2013, The Journal of Neuroscience.

[61]  C. Gilbert,et al.  Perceptual learning and top-down influences in primary visual cortex , 2004, Nature Neuroscience.

[62]  Jeffrey P. Gavornik,et al.  Higher brain functions served by the lowly rodent primary visual cortex , 2014, Learning & memory.

[63]  C. Gilbert,et al.  Top-down influences on visual processing , 2013, Nature Reviews Neuroscience.

[64]  V. Kotak,et al.  Cortical Synaptic Inhibition Declines during Auditory Learning , 2015, The Journal of Neuroscience.

[65]  Maik C. Stüttgen,et al.  The Head-fixed Behaving Rat—Procedures and Pitfalls , 2010, Somatosensory & motor research.

[66]  U. Mitzdorf Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. , 1985, Physiological reviews.

[67]  P. Maquet,et al.  Neural correlates of perceptual learning: A functional MRI study of visual texture discrimination , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Neil A. Macmillan,et al.  Detection Theory: A User's Guide , 1991 .

[69]  John H. R. Maunsell,et al.  Effects of spatial attention on contrast response functions in macaque area V4. , 2006, Journal of neurophysiology.

[70]  R. Shapley,et al.  Contrast's effect on spatial summation by macaque V1 neurons , 1999, Nature Neuroscience.

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

[72]  C. Law,et al.  Neural correlates of perceptual learning in a sensory-motor, but not a sensory, cortical area , 2008, Nature Neuroscience.

[73]  W. Cleveland Robust Locally Weighted Regression and Smoothing Scatterplots , 1979 .

[74]  T Poggio,et al.  Fast perceptual learning in visual hyperacuity. , 1991, Science.

[75]  J. Maunsell,et al.  The Effect of Perceptual Learning on Neuronal Responses in Monkey Visual Area V4 , 2004, The Journal of Neuroscience.

[76]  Ovidiu F. Jurjuţ,et al.  Effects of Locomotion Extend throughout the Mouse Early Visual System , 2014, Current Biology.

[77]  G. Orban,et al.  Practising orientation identification improves orientation coding in V1 neurons , 2001, Nature.

[78]  J. Maunsell,et al.  Psychophysical measurement of contrast sensitivity in the behaving mouse. , 2012, Journal of neurophysiology.

[79]  Andrew T. Smith,et al.  Attentional modulation in visual cortex is modified during perceptual learning , 2011, Neuropsychologia.

[80]  Chang-Bing Huang,et al.  Perceptual Learning Improves Contrast Sensitivity of V1 Neurons in Cats , 2010, Current Biology.

[81]  G. Orban,et al.  Human perceptual learning in identifying the oblique orientation: retinotopy, orientation specificity and monocularity. , 1995, The Journal of physiology.

[82]  G. Leuba,et al.  Postnatal development of the mouse cerebral neocortex. II. Quantitative cytoarchitectonics of visual and auditory areas. , 1977, Journal fur Hirnforschung.

[83]  Mark F Bear,et al.  Visual Experience Induces Long-Term Potentiation in the Primary Visual Cortex , 2010, The Journal of Neuroscience.

[84]  S. Treue,et al.  Attentional Modulation Strength in Cortical Area MT Depends on Stimulus Contrast , 2002, Neuron.

[85]  R. Desimone,et al.  Attention Increases Sensitivity of V4 Neurons , 2000, Neuron.

[86]  Li I. Zhang,et al.  Intervening Inhibition Underlies Simple-Cell Receptive Field Structure in Visual Cortex , 2009, Nature Neuroscience.

[87]  C. Schroeder,et al.  Layer Specific Sharpening of Frequency Tuning by Selective Attention in Primary Auditory Cortex , 2014, The Journal of Neuroscience.

[88]  R. Rescorla,et al.  A theory of Pavlovian conditioning : Variations in the effectiveness of reinforcement and nonreinforcement , 1972 .

[89]  P. Lennie,et al.  Early and Late Mechanisms of Surround Suppression in Striate Cortex of Macaque , 2005, The Journal of Neuroscience.

[90]  Mark F. Bear,et al.  How Monocular Deprivation Shifts Ocular Dominance in Visual Cortex of Young Mice , 2004, Neuron.

[91]  M. Stephens,et al.  K-Sample Anderson–Darling Tests , 1987 .

[92]  Mark F. Bear,et al.  Visual recognition memory, manifest as long-term habituation, requires synaptic plasticity in V1 , 2015, Nature Neuroscience.

[93]  R. Quian Quiroga,et al.  Unsupervised Spike Detection and Sorting with Wavelets and Superparamagnetic Clustering , 2004, Neural Computation.

[94]  John H. R. Maunsell,et al.  Physiological correlates of perceptual learning in monkey V1 and V2. , 2002, Journal of neurophysiology.