Homeostatic mechanisms regulate distinct aspects of cortical circuit dynamics

Significance Despite decades of intense studies on homeostasis, network properties undergoing homeostatic regulation remain elusive. Furthermore, whether diverse forms of homeostatic plasticity are simply redundant or serve distinct functions is unclear. Here, our data show that functional correlations are subject to homeostatic regulation, both in terms of average amplitude and their structure. A computational model demonstrates that synaptic scaling is essential for the restoration of correlations and network structure, whereas intrinsic plasticity is crucial for the recovery of firing rates after perturbations, suggesting that synaptic scaling and intrinsic plasticity distinctly contribute to homeostatic regulation. Homeostasis is indispensable to counteract the destabilizing effects of Hebbian plasticity. Although it is commonly assumed that homeostasis modulates synaptic strength, membrane excitability, and firing rates, its role at the neural circuit and network level is unknown. Here, we identify changes in higher-order network properties of freely behaving rodents during prolonged visual deprivation. Strikingly, our data reveal that functional pairwise correlations and their structure are subject to homeostatic regulation. Using a computational model, we demonstrate that the interplay of different plasticity and homeostatic mechanisms can capture the initial drop and delayed recovery of firing rates and correlations observed experimentally. Moreover, our model indicates that synaptic scaling is crucial for the recovery of correlations and network structure, while intrinsic plasticity is essential for the rebound of firing rates, suggesting that synaptic scaling and intrinsic plasticity can serve distinct functions in homeostatically regulating network dynamics.

[1]  Keith B. Hengen,et al.  Firing Rate Homeostasis in Visual Cortex of Freely Behaving Rodents , 2013, Neuron.

[2]  E. Marder,et al.  Activity-dependent regulation of conductances in model neurons. , 1993, Science.

[3]  D. Debanne,et al.  Long-term plasticity of intrinsic excitability: learning rules and mechanisms. , 2003, Learning & memory.

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

[5]  Georg B. Keller,et al.  Subnetwork-Specific Homeostatic Plasticity in Mouse Visual Cortex In Vivo , 2015, Neuron.

[6]  K. Miller,et al.  Modeling the Dynamic Interaction of Hebbian and Homeostatic Plasticity , 2014, Neuron.

[7]  P. Roelfsema,et al.  The threshold for conscious report: Signal loss and response bias in visual and frontal cortex , 2018, Science.

[8]  Julijana Gjorgjieva,et al.  Rapid and active stabilization of visual cortical firing rates across light–dark transitions , 2019, Proceedings of the National Academy of Sciences.

[9]  Mark Hübener,et al.  Critical-period plasticity in the visual cortex. , 2012, Annual review of neuroscience.

[10]  P. J. Sjöström,et al.  Rate, Timing, and Cooperativity Jointly Determine Cortical Synaptic Plasticity , 2001, Neuron.

[11]  Petr Znamenskiy,et al.  Functional selectivity and specific connectivity of inhibitory neurons in primary visual cortex , 2018, bioRxiv.

[12]  M. Sheng,et al.  Critical Role of CDK5 and Polo-like Kinase 2 in Homeostatic Synaptic Plasticity during Elevated Activity , 2008, Neuron.

[13]  Lisandro Montangie,et al.  Autonomous emergence of connectivity assemblies via spike triplet interactions , 2020, PLoS computational biology.

[14]  Michael P Stryker,et al.  TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation , 2008, Nature Neuroscience.

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

[16]  Robert C. Froemke,et al.  Inhibitory and Excitatory Spike-Timing-Dependent Plasticity in the Auditory Cortex , 2015, Neuron.

[17]  M. Bear,et al.  Thalamic activity that drives visual cortical plasticity , 2009, Nature Neuroscience.

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

[19]  S. Nelson,et al.  Potentiation of cortical inhibition by visual deprivation , 2006, Nature.

[20]  S. Nelson,et al.  Homeostatic plasticity in the developing nervous system , 2004, Nature Reviews Neuroscience.

[21]  Gina G. Turrigiano,et al.  All for One But Not One for All: Excitatory Synaptic Scaling and Intrinsic Excitability Are Coregulated by CaMKIV, Whereas Inhibitory Synaptic Scaling Is Under Independent Control , 2017, The Journal of Neuroscience.

[22]  A. Litwin-Kumar,et al.  Formation and maintenance of neuronal assemblies through synaptic plasticity , 2014, Nature Communications.

[23]  Christian Tetzlaff,et al.  The interplay of synaptic plasticity and scaling enables self-organized formation and allocation of multiple memory representations , 2018, bioRxiv.

[24]  Niraj S. Desai,et al.  Plasticity in the intrinsic excitability of cortical pyramidal neurons , 1999, Nature Neuroscience.

[25]  R. Malenka,et al.  Synaptic scaling mediated by glial TNF-α , 2006, Nature.

[26]  Brian Zingg,et al.  Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar and Cell-Type Specificity. , 2016, Cerebral cortex.

[27]  Jaime de la Rocha,et al.  Supplementary Information for the article ‘ Correlation between neural spike trains increases with firing rate ’ , 2007 .

[28]  Henning Sprekeler,et al.  Inhibitory Plasticity Balances Excitation and Inhibition in Sensory Pathways and Memory Networks , 2011, Science.

[29]  G. Turrigiano Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement. , 2011, Annual review of neuroscience.

[30]  Romain Brette,et al.  Generation of Correlated Spike Trains , 2009, Neural Computation.

[31]  C. Clopath,et al.  Diverse homeostatic responses to visual deprivation by uncovering recurrent subnetworks , 2018, bioRxiv.

[32]  B. McNaughton,et al.  Paradoxical Effects of External Modulation of Inhibitory Interneurons , 1997, The Journal of Neuroscience.

[33]  Stephen D. Van Hooser,et al.  Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake , 2016, Cell.

[34]  Tobias Bonhoeffer,et al.  Cell-specific restoration of stimulus preference after monocular deprivation in the visual cortex , 2016, Science.

[35]  W. Gerstner,et al.  Triplets of Spikes in a Model of Spike Timing-Dependent Plasticity , 2006, The Journal of Neuroscience.

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

[37]  Mark F. Bear,et al.  Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex , 2007, Proceedings of the National Academy of Sciences.

[38]  D. Debanne,et al.  Enhanced Intrinsic Excitability in Basket Cells Maintains Excitatory-Inhibitory Balance in Hippocampal Circuits , 2013, Neuron.

[39]  Wulfram Gerstner,et al.  Synaptic Plasticity in Neural Networks Needs Homeostasis with a Fast Rate Detector , 2013, PLoS Comput. Biol..

[40]  Peter Dayan,et al.  Theoretical Neuroscience: Computational and Mathematical Modeling of Neural Systems , 2001 .

[41]  G. Turrigiano,et al.  Synaptic and Intrinsic Homeostatic Mechanisms Cooperate to Increase L2/3 Pyramidal Neuron Excitability during a Late Phase of Critical Period Plasticity , 2013, The Journal of Neuroscience.

[42]  Brent Doiron,et al.  Training and spontaneous reinforcement of neuronal assemblies by spike timing plasticity , 2016, bioRxiv.

[43]  Everton J. Agnes,et al.  Diverse synaptic plasticity mechanisms orchestrated to form and retrieve memories in spiking neural networks , 2015, Nature Communications.

[44]  J. Isaac,et al.  Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation , 2010, Nature Neuroscience.

[45]  Richard Hans Robert Hahnloser,et al.  Spike-Time-Dependent Plasticity and Heterosynaptic Competition Organize Networks to Produce Long Scale-Free Sequences of Neural Activity , 2010, Neuron.

[46]  Y. Goda,et al.  Activity-Dependent Regulation of Synaptic AMPA Receptor Composition and Abundance by β3 Integrins , 2008, Neuron.

[47]  Thomas K. Berger,et al.  A synaptic organizing principle for cortical neuronal groups , 2011, Proceedings of the National Academy of Sciences.

[48]  J. Pfister,et al.  A triplet spike-timing–dependent plasticity model generalizes the Bienenstock–Cooper–Munro rule to higher-order spatiotemporal correlations , 2011, Proceedings of the National Academy of Sciences.

[49]  Georg B. Keller,et al.  Synaptic Scaling and Homeostatic Plasticity in the Mouse Visual Cortex In Vivo , 2013, Neuron.

[50]  E. Callaway,et al.  Excitatory cortical neurons form fine-scale functional networks , 2005, Nature.

[51]  Ralf Wessel,et al.  Cortical Circuit Dynamics Are Homeostatically Tuned to Criticality In Vivo , 2019, Neuron.

[52]  Tim P Vogels,et al.  Signal Propagation and Logic Gating in Networks of Integrate-and-Fire Neurons , 2005, The Journal of Neuroscience.

[53]  M. Grubb,et al.  Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability , 2010, Nature.

[54]  E. Marder,et al.  Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  Nathaniel J. Miska,et al.  Sensory experience inversely regulates feedforward and feedback excitation-inhibition ratio in rodent visual cortex , 2018, eLife.

[56]  L. Abbott,et al.  Synaptic plasticity: taming the beast , 2000, Nature Neuroscience.

[57]  Jing Wu,et al.  Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors , 2006, Neuron.

[58]  M. Bear,et al.  Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[59]  Georg B. Keller,et al.  Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss , 2017, Neuron.

[60]  Niraj S. Desai,et al.  Activity-dependent scaling of quantal amplitude in neocortical neurons , 1998, Nature.

[61]  Kevin F. H. Lee,et al.  Metaplasticity at CA1 Synapses by Homeostatic Control of Presynaptic Release Dynamics. , 2017, Cell reports.