Sleep-Stage-Specific Regulation of Cortical Excitation and Inhibition

Sleep is characterized by unique patterns of cortical activity alternating between the stages of slow-wave sleep (SWS) and rapid-eye movement (REM) sleep. How these patterns relate to the balanced activity of excitatory pyramidal cells and inhibitory interneurons in cortical circuits is unknown. We investigated cortical network activity during wakefulness, SWS, and REM sleep globally and locally using in vivo calcium imaging in mice. Wide-field imaging revealed a reduction in pyramidal cell activity during SWS compared with wakefulness and, unexpectedly, a further profound reduction in activity during REM sleep. Two-photon imaging on local circuits showed that this suppression of activity during REM sleep was accompanied by activation of parvalbumin (PV)+ interneurons, but not of somatostatin (SOM)+ interneurons. PV+ interneurons most active during wakefulness were also most active during REM sleep. Our results reveal a sleep-stage-specific regulation of the cortical excitation/inhibition balance, with PV+ interneurons conveying maximum inhibition during REM sleep, which might help shape memories in these networks.

[1]  M. Steriade,et al.  Natural waking and sleep states: a view from inside neocortical neurons. , 2001, Journal of neurophysiology.

[2]  R. McCarley,et al.  Control of sleep and wakefulness. , 2012, Physiological reviews.

[3]  Karel Svoboda,et al.  Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice , 2010, Nature.

[4]  Paul Antoine Salin,et al.  The supramammillary nucleus and the claustrum activate the cortex during REM sleep , 2015, Science Advances.

[5]  G. Tononi,et al.  Dreaming and the brain: from phenomenology to neurophysiology , 2010, Trends in Cognitive Sciences.

[6]  C. Degueldre,et al.  Functional neuroanatomy of human rapid-eye-movement sleep and dreaming , 1996, Nature.

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

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

[9]  Fuad G. Gwadry,et al.  Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep. , 1998, Science.

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

[11]  Karel Svoboda,et al.  ScanImage: Flexible software for operating laser scanning microscopes , 2003, Biomedical engineering online.

[12]  J. Born,et al.  About sleep's role in memory. , 2013, Physiological reviews.

[13]  D. McCormick,et al.  Neocortical Network Activity In Vivo Is Generated through a Dynamic Balance of Excitation and Inhibition , 2006, The Journal of Neuroscience.

[14]  D. Neckelmann,et al.  The reliability and functional validity of visual and semiautomatic sleep/wake scoring in the Møll-Wistar rat. , 1994, Sleep.

[15]  M. Stryker A Neural Circuit That Controls Cortical State, Plasticity, and the Gain of Sensory Responses in Mouse. , 2014, Cold Spring Harbor symposia on quantitative biology.

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

[17]  W. Gerstner,et al.  Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex. , 2012, Journal of neurophysiology.

[18]  T. Freund,et al.  gamma-Aminobutyric acid-containing basal forebrain neurons innervate inhibitory interneurons in the neocortex. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

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

[20]  J. Lübke,et al.  Efficacy and connectivity of intracolumnar pairs of layer 2/3 pyramidal cells in the barrel cortex of juvenile rats , 2006, The Journal of physiology.

[21]  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.

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

[23]  Henry J. Alitto,et al.  Function of inhibition in visual cortical processing , 2010, Current Opinion in Neurobiology.

[24]  Demetris K. Roumis,et al.  Functional Specialization of Mouse Higher Visual Cortical Areas , 2011, Neuron.

[25]  Arno C. Schmitt,et al.  Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A , 2011, Proceedings of the National Academy of Sciences.

[26]  Colin J. Akerman,et al.  Refining the roles of GABAergic signaling during neural circuit formation , 2007, Trends in Neurosciences.

[27]  I. Fried,et al.  Regional Slow Waves and Spindles in Human Sleep , 2011, Neuron.

[28]  J A Hobson,et al.  Cortical unit activity in sleep and waking. , 1971, Electroencephalography and clinical neurophysiology.

[29]  G. Tononi,et al.  Auditory responses and stimulus-specific adaptation in rat auditory cortex are preserved across NREM and REM sleep. , 2015, Cerebral cortex.

[30]  G. Buzsáki,et al.  REM Sleep Reorganizes Hippocampal Excitability , 2012, Neuron.

[31]  K. Svoboda,et al.  The Functional Microarchitecture of the Mouse Barrel Cortex , 2007, Neuroscience Research.

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

[33]  Nathan C. Klapoetke,et al.  Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance , 2015, Neuron.

[34]  E. Evarts TEMPORAL PATTERNS OF DISCHARGE OF PYRAMIDAL TRACT NEURONS DURING SLEEP AND WAKING IN THE MONKEY. , 1964, Journal of neurophysiology.

[35]  Abigail Morrison,et al.  Dynamic stability of sequential stimulus representations in adapting neuronal networks , 2014, Front. Comput. Neurosci..

[36]  B. Sakmann,et al.  Dynamic Receptive Fields of Reconstructed Pyramidal Cells in Layers 3 and 2 of Rat Somatosensory Barrel Cortex , 2003, The Journal of physiology.

[37]  J. Born,et al.  Peripheral and central blockade of interleukin-6 trans-signaling differentially affects sleep architecture , 2015, Brain, Behavior, and Immunity.

[38]  K. Deisseroth,et al.  Parvalbumin neurons and gamma rhythms enhance cortical circuit performance , 2009, Nature.

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

[40]  D. Tank,et al.  In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons , 1999, Nature Neuroscience.

[41]  C. Petersen Cell-type specific function of GABAergic neurons in layers 2 and 3 of mouse barrel cortex , 2014, Current Opinion in Neurobiology.

[42]  Arthur W. Wetzel,et al.  Network anatomy and in vivo physiology of visual cortical neurons , 2011, Nature.

[43]  Y. Kubota,et al.  GABAergic cell subtypes and their synaptic connections in rat frontal cortex. , 1997, Cerebral cortex.

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

[45]  Jessica A. Cardin,et al.  Driving fast-spiking cells induces gamma rhythm and controls sensory responses , 2009, Nature.

[46]  Sreekanth H. Chalasani,et al.  Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators , 2009, Nature Methods.

[47]  P. Somogyi,et al.  Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo , 2003, Nature.

[48]  S. Arber,et al.  A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling , 2005, PLoS biology.

[49]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

[50]  Johannes C. Dahmen,et al.  Thalamic nuclei convey diverse contextual information to layer 1 of visual cortex , 2015, Nature Neuroscience.

[51]  Nicholas J. Priebe,et al.  Local Integration Accounts for Weak Selectivity of Mouse Neocortical Parvalbumin Interneurons , 2015, Neuron.

[52]  T. Murphy,et al.  Mesoscale Transcranial Spontaneous Activity Mapping in GCaMP3 Transgenic Mice Reveals Extensive Reciprocal Connections between Areas of Somatomotor Cortex , 2014, The Journal of Neuroscience.

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

[54]  A. Braun,et al.  Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. , 1997, Brain : a journal of neurology.

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

[56]  Seiji Nishino,et al.  Basal forebrain circuit for sleep-wake control , 2015, Nature Neuroscience.

[57]  N. Spruston,et al.  Diversity and dynamics of dendritic signaling. , 2000, Science.

[58]  G. Tononi,et al.  Cortical Firing and Sleep Homeostasis , 2009, Neuron.

[59]  T. Lemberger,et al.  A CamKIIalpha iCre BAC allows brain-specific gene inactivation. , 2001, Genesis.

[60]  A. Braun,et al.  Regional cerebral blood flow throughout the sleep- wake cycle , 1997 .