Cooperative Subnetworks of Molecularly Similar Interneurons in Mouse Neocortex

Simultaneous co-activation of neocortical neurons is likely critical for brain computations ranging from perception and motor control to memory and cognition. While co-activation of excitatory principal cells (PCs) during ongoing activity has been extensively studied, that of inhibitory interneurons (INs) has received little attention. Here, we show in vivo and in vitro that members of two non-overlapping neocortical IN populations, expressing somatostatin (SOM) or vasoactive intestinal peptide (VIP), are active as populations rather than individually. We demonstrate a variety of synergistic mechanisms, involving population-specific local excitation, GABAergic disinhibition and excitation through electrical coupling, which likely underlie IN population co-activity. Firing of a few SOM or VIP INs recruits additional members within the cell type via GABAergic and cholinergic mechanisms, thereby amplifying the output of the population as a whole. Our data suggest that IN populations work as cooperative units, thus generating an amplifying nonlinearity in their circuit output.

[1]  K. Harris,et al.  Laminar Structure of Spontaneous and Sensory-Evoked Population Activity in Auditory Cortex , 2009, Neuron.

[2]  G. Fishell,et al.  A disinhibitory circuit mediates motor integration in the somatosensory cortex , 2013, Nature Neuroscience.

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

[4]  R. Reid,et al.  Cellular Imaging of Visual Cortex Reveals the Spatial and Functional Organization of Spontaneous Activity , 2010, Front. Integr. Neurosci..

[5]  A. Agmon,et al.  Short-Term Plasticity of Unitary Inhibitory-to-Inhibitory Synapses Depends on the Presynaptic Interneuron Subtype , 2012, The Journal of Neuroscience.

[6]  Karen L. Smith,et al.  Novel Hippocampal Interneuronal Subtypes Identified Using Transgenic Mice That Express Green Fluorescent Protein in GABAergic Interneurons , 2000, The Journal of Neuroscience.

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

[8]  H. Markram,et al.  Disynaptic Inhibition between Neocortical Pyramidal Cells Mediated by Martinotti Cells , 2007, Neuron.

[9]  E. Callaway,et al.  Fine-scale specificity of cortical networks depends on inhibitory cell type and connectivity , 2005, Nature Neuroscience.

[10]  R. Reid,et al.  Broadly Tuned Response Properties of Diverse Inhibitory Neuron Subtypes in Mouse Visual Cortex , 2010, Neuron.

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

[12]  G. Fishell,et al.  Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons , 2011, Developmental neurobiology.

[13]  S. Rumpel,et al.  Discrete Neocortical Dynamics Predict Behavioral Categorization of Sounds , 2012, Neuron.

[14]  B. Connors,et al.  Two networks of electrically coupled inhibitory neurons in neocortex , 1999, Nature.

[15]  Adam Kepecs,et al.  From circuit motifs to computations: mapping the behavioral repertoire of cortical interneurons , 2014, Current Opinion in Neurobiology.

[16]  Hongkui Zeng,et al.  Differential tuning and population dynamics of excitatory and inhibitory neurons reflect differences in local intracortical connectivity , 2011, Nature Neuroscience.

[17]  Wei-Cheng Chang,et al.  Supplementary Material for Long-range and local circuits for top-down modulation of visual cortical processing , 2014 .

[18]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[19]  Rafael Yuste,et al.  Two-photon optogenetics of dendritic spines and neural circuits in 3D , 2012, Nature Methods.

[20]  Y. Dan,et al.  Long-range and local circuits for top-down modulation of visual cortex processing , 2014, Science.

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

[22]  P. Golshani,et al.  Direct Reactivation of a Coherent Neocortical Memory of Context , 2014, Neuron.

[23]  A. Agmon,et al.  Distinct Subtypes of Somatostatin-Containing Neocortical Interneurons Revealed in Transgenic Mice , 2006, The Journal of Neuroscience.

[24]  R. Hen,et al.  The participation of cortical amygdala in innate, odor-driven behavior , 2014, Nature.

[25]  Joshua I. Sanders,et al.  Cortical interneurons that specialize in disinhibitory control , 2013, Nature.

[26]  G. Fishell,et al.  Interneuron cell types are fit to function , 2014, Nature.

[27]  T. Tsumoto,et al.  GABAergic Neurons Are Less Selective to Stimulus Orientation than Excitatory Neurons in Layer II/III of Visual Cortex, as Revealed by In Vivo Functional Ca2+ Imaging in Transgenic Mice , 2007, The Journal of Neuroscience.

[28]  R. Yuste,et al.  Decorrelating Action of Inhibition in Neocortical Networks , 2013, The Journal of Neuroscience.

[29]  F. Attneave,et al.  The Organization of Behavior: A Neuropsychological Theory , 1949 .

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

[31]  Hannah Monyer,et al.  Functional Characterization of Intrinsic Cholinergic Interneurons in the Cortex , 2007, The Journal of Neuroscience.

[32]  Nathan R. Wilson,et al.  Response Features of Parvalbumin-Expressing Interneurons Suggest Precise Roles for Subtypes of Inhibition in Visual Cortex , 2010, Neuron.

[33]  Pico Caroni,et al.  Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning , 2013, Nature.

[34]  B. Connors,et al.  Two dynamically distinct inhibitory networks in layer 4 of the neocortex. , 2003, Journal of neurophysiology.

[35]  Michael Häusser,et al.  Target-Specific Effects of Somatostatin-Expressing Interneurons on Neocortical Visual Processing , 2013, The Journal of Neuroscience.

[36]  George H. Denfield,et al.  Pupil Fluctuations Track Fast Switching of Cortical States during Quiet Wakefulness , 2014, Neuron.

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

[38]  Massimo Scanziani,et al.  Supralinear increase of recurrent inhibition during sparse activity in the somatosensory cortex , 2007, Nature Neuroscience.

[39]  S. Hestrin,et al.  A network of fast-spiking cells in the neocortex connected by electrical synapses , 1999, Nature.

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

[41]  M. Scanziani,et al.  Inhibition of Inhibition in Visual Cortex: The Logic of Connections Between Molecularly Distinct Interneurons , 2013, Nature Neuroscience.

[42]  S. Coultrap,et al.  CaMKII regulation in information processing and storage , 2012, Trends in Neurosciences.

[43]  M. Wilson,et al.  Coordinated memory replay in the visual cortex and hippocampus during sleep , 2007, Nature Neuroscience.

[44]  G. Tamás,et al.  Gap-Junctional Coupling between Neurogliaform Cells and Various Interneuron Types in the Neocortex , 2005, The Journal of Neuroscience.

[45]  G. Knott,et al.  Experience and Activity-Dependent Maturation of Perisomatic GABAergic Innervation in Primary Visual Cortex during a Postnatal Critical Period , 2004, The Journal of Neuroscience.

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

[47]  P. Somogyi,et al.  Target-cell-specific facilitation and depression in neocortical circuits , 1998, Nature Neuroscience.

[48]  A. Agmon,et al.  Submillisecond Firing Synchrony between Different Subtypes of Cortical Interneurons Connected Chemically But Not Electrically , 2011, The Journal of Neuroscience.

[49]  Axel Schleicher,et al.  The innervation of parvalbumin‐containing interneurons by VIP‐immunopositive interneurons in the primary somatosensory cortex of the adult rat , 2007, The European journal of neuroscience.

[50]  Martin Vinck,et al.  Arousal and Locomotion Make Distinct Contributions to Cortical Activity Patterns and Visual Encoding , 2014, Neuron.

[51]  G. Shepherd,et al.  The neocortical circuit: themes and variations , 2015, Nature Neuroscience.