Overproduction of Neurons Is Correlated with Enhanced Cortical Ensembles and Increased Perceptual Discrimination.

Brains vary greatly in neuronal number and density, even across individuals within the same species, yet it remains unclear whether such variation leads to differences in brain function or behavior. By imaging cortical activity of a mouse model in which neuronal production is moderately enhanced in utero, we find that animals with more cortical neurons also develop enhanced functional correlations and more distinct neuronal ensembles in primary visual cortex. These mice also have sharper orientation discrimination in their visual behavior. These results unveil a correlation between neuronal ensembles and behavior and suggest that neuronal number is linked to functional modularity and perceptual discrimination of visual cortex. By experimentally linking differences in neuronal number and behavior, our findings could help explain how evolutionary and developmental variability of individual and species brain size may lead to perceptual and cognitive differences.

[1]  R. Yuste.  From the neuron doctrine to neural networks , 2015, Nature Reviews Neuroscience.

[2]  Leonard E. White,et al.  Vision and Cortical Map Development , 2007, Neuron.

[3]  W. Fitch,et al.  Birds have primate-like numbers of neurons in the forebrain , 2016, Proceedings of the National Academy of Sciences.

[4]  Jon H. Kaas,et al.  Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size , 2014, Front. Neuroanat..

[5]  S. Herculano‐Houzel.  The Human Brain in Numbers: A Linearly Scaled-up Primate Brain , 2009, Front. Hum. Neurosci..

[6]  I. Soltesz,et al.  Spatially clustered neuronal assemblies comprise the microstructure of synchrony in chronically epileptic networks , 2013, Proceedings of the National Academy of Sciences.

[7]  N. Ip,et al.  Axin Directs the Amplification and Differentiation of Intermediate Progenitors in the Developing Cerebral Cortex , 2013, Neuron.

[8]  Yuji Ikegaya,et al.  Synfire Chains and Cortical Songs: Temporal Modules of Cortical Activity , 2004, Science.

[9]  G. Edelman.  Neural Darwinism: Selection and reentrant signaling in higher brain function , 1993, Neuron.

[10]  Woong Sun,et al.  Adaptive roles of programmed cell death during nervous system development. , 2006, Annual review of neuroscience.

[11]  Kira E. Poskanzer,et al.  Astrocytes regulate cortical state switching in vivo , 2016, Proceedings of the National Academy of Sciences.

[12]  Geraint Rees,et al.  Variability in visual cortex size reflects tradeoff between local orientation sensitivity and global orientation modulation , 2013, Nature Communications.

[13]  W. Gan,et al.  Stably maintained dendritic spines are associated with lifelong memories , 2009, Nature.

[14]  P. J. Sjöström,et al.  Functional specificity of local synaptic connections in neocortical networks , 2011, Nature.

[15]  D. Ferster,et al.  Synchronous Membrane Potential Fluctuations in Neurons of the Cat Visual Cortex , 1999, Neuron.

[16]  David Pfau,et al.  Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data , 2016, Neuron.

[17]  K. Harris.  Neural signatures of cell assembly organization , 2005, Nature Reviews Neuroscience.

[18]  Y. Dan,et al.  Clonally Related Visual Cortical Neurons Show Similar Stimulus Feature Selectivity , 2012, Nature.

[19]  K. Ohki,et al.  Similarity of Visual Selectivity among Clonally Related Neurons in Visual Cortex , 2012, Neuron.

[20]  R. Yuste,et al.  Visual stimuli recruit intrinsically generated cortical ensembles , 2014, Proceedings of the National Academy of Sciences.

[21]  Zengcai V. Guo,et al.  Procedures for Behavioral Experiments in Head-Fixed Mice , 2014, PloS one.

[22]  S. Shi,et al.  Specific synapses develop preferentially among sister excitatory neurons in the neocortex , 2009, Nature.

[23]  L. Paninski,et al.  Simultaneous Multi-plane Imaging of Neural Circuits , 2016, Neuron.

[24]  M. Siniscalchi,et al.  Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior , 2016, Nature Neuroscience.

[25]  K. Harris,et al.  Spontaneous Events Outline the Realm of Possible Sensory Responses in Neocortical Populations , 2009, Neuron.

[26]  R. Yuste,et al.  Attractor dynamics of network UP states in the neocortex , 2003, Nature.

[27]  Peter Sterling,et al.  Principles of Neural Design , 2015 .

[28]  R. Yuste,et al.  Imprinting and recalling cortical ensembles , 2016, Science.

[29]  Terrence J. Sejnowski,et al.  Inhibition synchronizes sparsely connected cortical neurons within and between columns in realistic network models , 1996, Journal of Computational Neuroscience.

[30]  R. Williams,et al.  The control of neuron number. , 1988, Annual review of neuroscience.

[31]  A. Grinvald,et al.  Spontaneously emerging cortical representations of visual attributes , 2003, Nature.

[32]  David A. McCormick,et al.  Competing Neural Ensembles in Motor Cortex Gate Goal-Directed Motor Output , 2015, Neuron.

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

[34]  J. Csicsvari,et al.  Organization of cell assemblies in the hippocampus , 2003, Nature.

[35]  G. Roth,et al.  Evolution of the brain and intelligence , 2005, Trends in Cognitive Sciences.

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

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

[38]  A. Kriegstein,et al.  Development and Evolution of the Human Neocortex , 2011, Cell.

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

[40]  D. R. Muir,et al.  Functional organization of excitatory synaptic strength in primary visual cortex , 2015, Nature.

[41]  Giorgio M. Innocenti,et al.  Exuberance in the development of cortical networks , 2005, Nature Reviews Neuroscience.

[42]  Maro G. Machizawa,et al.  Neural activity predicts individual differences in visual working memory capacity , 2004, Nature.

[43]  Rafael Yuste,et al.  Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters , 1991, Neuron.

[44]  Rafael Yuste,et al.  Astrocytic regulation of cortical UP states , 2011, Proceedings of the National Academy of Sciences.

[45]  Michael J. Berry,et al.  Weak pairwise correlations imply strongly correlated network states in a neural population , 2005, Nature.

[46]  Rosa Cossart,et al.  Awake hippocampal reactivations project onto orthogonal neuronal assemblies , 2016, Science.

[47]  Brett J. Graham,et al.  Anatomy and function of an excitatory network in the visual cortex , 2016, Nature.

[48]  Maria V. Sanchez-Vives,et al.  Cellular and network mechanisms of rhythmic recurrent activity in neocortex , 2000, Nature Neuroscience.

[49]  E. Nordeen,et al.  Individual variation in neuron number predicts differences in the propensity for avian vocal imitation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[50]  D. B. Leitch,et al.  Neuron densities vary across and within cortical areas in primates , 2010, Proceedings of the National Academy of Sciences.

[51]  Charles F Stevens,et al.  Predicting visual acuity from the structure of visual cortex , 2015, Proceedings of the National Academy of Sciences.

[52]  M. Fox,et al.  Individual Variability in Functional Connectivity Architecture of the Human Brain , 2013, Neuron.

[53]  D. Hubel,et al.  Receptive fields of single neurones in the cat's striate cortex , 1959, The Journal of physiology.

[54]  D. O. Hebb,et al.  The organization of behavior , 1988 .

[55]  W. Yung,et al.  Overproduction of upper-layer neurons in the neocortex leads to autism-like features in mice. , 2014, Cell reports.

[56]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[57]  K. Deisseroth,et al.  Optogenetic stimulation of a hippocampal engram activates fear memory recall , 2012, Nature.

[58]  Alcino J. Silva,et al.  A shared neural ensemble links distinct contextual memories encoded close in time , 2016, Nature.

[59]  Brendon O. Watson,et al.  Internal Dynamics Determine the Cortical Response to Thalamic Stimulation , 2005, Neuron.

[60]  A. Pouget,et al.  Neural correlations, population coding and computation , 2006, Nature Reviews Neuroscience.

[61]  Rafael Yuste,et al.  Parvalbumin-Positive Interneurons Regulate Neuronal Ensembles in Visual Cortex , 2018, Cerebral cortex.