Network activity and spike discharge oscillations in cortical slice cultures from neonatal rat

Network bursts and oscillations are forms of spontaneous activity in cortical circuits that have been described in vivo and in vitro. Searching for mechanisms involved in their generation, we investigated the collective network activity and spike discharge oscillations in cortical slice cultures of neonatal rats, combining multielectrode arrays with patch clamp recordings from individual neurons. The majority of these cultures showed spontaneous collective network activity [population bursts (PBs)] that could be described as neuronal avalanches. The largest of these PBs were followed by fast spike discharge oscillations in the beta to theta range, and sometimes additional repetitive PBs, together forming seizure‐like episodes. During such episodes, all neurons showed sustained depolarization with increased spike rates. However, whereas regular‐spiking (RS) and fast‐spiking (FS) neurons fired during the PBs, only the FS neurons fired during the fast oscillations. Blockade of N‐methyl‐d‐aspartate receptors reduced the depolarization and suppressed both the increased FS neuron firing and the oscillations. To investigate the generation of PBs, we studied the network responses to electrical stimulation. For most of the stimulation sites, the relationship between the stimulated inputs and the evoked PBs was linear. From a few stimulation sites, however, large PBs could be evoked with small inputs, indicating the activation of hub circuits. Taken together, our findings suggests that the oscillations originate from recurrent inhibition in local networks of depolarized inhibitory FS interneurons, whereas the PBs originate from recurrent excitation in networks of RS and FS neurons that is initiated in hub circuits.

[1]  D. Plenz,et al.  The organizing principles of neuronal avalanches: cell assemblies in the cortex? , 2007, Trends in Neurosciences.

[2]  Rafael Yuste,et al.  Persistently Active, Pacemaker-Like Neurons in Neocortex , 2007, Front. Neurosci..

[3]  Albert Compte,et al.  Spontaneous High-Frequency (10–80 Hz) Oscillations during Up States in the Cerebral Cortex In Vitro , 2008, The Journal of Neuroscience.

[4]  B. Connors,et al.  A network of electrically coupled interneurons drives synchronized inhibition in neocortex , 2000, Nature Neuroscience.

[5]  G. Tamás,et al.  Cholinergic activation and tonic excitation induce persistent gamma oscillations in mouse somatosensory cortex in vitro , 1998, The Journal of physiology.

[6]  John M. Beggs,et al.  Neuronal Avalanches in Neocortical Circuits , 2003, The Journal of Neuroscience.

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

[8]  D. Prince,et al.  Baseline glutamate levels affect group I and II mGluRs in layer V pyramidal neurons of rat sensorimotor cortex. , 2003, Journal of neurophysiology.

[9]  Jürg Streit,et al.  INaP underlies intrinsic spiking and rhythm generation in networks of cultured rat spinal cord neurons , 2004, The European journal of neuroscience.

[10]  T. Sejnowski,et al.  Cortical Enlightenment: Are Attentional Gamma Oscillations Driven by ING or PING? , 2009, Neuron.

[11]  P. Wahle,et al.  Patterns of spontaneous activity and morphology of interneuron types in organotypic cortex and thalamus–cortex cultures , 1999, Neuroscience.

[12]  J. Jefferys,et al.  On the Synchronizing Mechanisms of Tetanically Induced Hippocampal Oscillations , 1999, The Journal of Neuroscience.

[13]  Mu Zhou,et al.  Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development , 2010, Nature.

[14]  Andreas Klaus,et al.  Multi-electrode Array Recordings of Neuronal Avalanches in Organotypic Cultures , 2011, Journal of visualized experiments : JoVE.

[15]  Woodrow L. Shew,et al.  Neuronal Avalanches Imply Maximum Dynamic Range in Cortical Networks at Criticality , 2009, The Journal of Neuroscience.

[16]  W. Singer,et al.  The gamma cycle , 2007, Trends in Neurosciences.

[17]  D. Plenz,et al.  Neuronal avalanches organize as nested theta- and beta/gamma-oscillations during development of cortical layer 2/3 , 2008, Proceedings of the National Academy of Sciences.

[18]  Jyh-Jang Sun,et al.  Self‐organization of repetitive spike patterns in developing neuronal networks in vitro , 2010, The European journal of neuroscience.

[19]  H. Lüscher,et al.  Transient rhythmic network activity in the somatosensory cortex evoked by distributed input in vitro , 2006, Neuroscience.

[20]  Rafael Yuste,et al.  UP States Protect Ongoing Cortical Activity from Thalamic Inputs , 2008, PloS one.

[21]  Jian-Young Wu,et al.  Propagating wave and irregular dynamics: spatiotemporal patterns of cholinergic theta oscillations in neocortex in vitro. , 2003, Journal of neurophysiology.

[22]  M Giugliano,et al.  Single-neuron discharge properties and network activity in dissociated cultures of neocortex. , 2004, Journal of neurophysiology.

[23]  Dean V Buonomano,et al.  Development and Plasticity of Spontaneous Activity and Up States in Cortical Organotypic Slices , 2007, The Journal of Neuroscience.

[24]  D. Plenz,et al.  Spontaneous cortical activity in awake monkeys composed of neuronal avalanches , 2009, Proceedings of the National Academy of Sciences.

[25]  John Rinzel,et al.  Synchronization of Electrically Coupled Pairs of Inhibitory Interneurons in Neocortex , 2007, The Journal of Neuroscience.

[26]  Jan-Marino Ramirez,et al.  Synchrony levels during evoked seizure-like bursts in mouse neocortical slices. , 2003, Journal of neurophysiology.

[27]  Jürg Streit,et al.  Mechanisms controlling bursting activity induced by disinhibition in spinal cord networks , 2002, The European journal of neuroscience.

[28]  R. Yuste,et al.  The Source of Afterdischarge Activity in Neocortical Tonic–Clonic Epilepsy , 2007, The Journal of Neuroscience.

[29]  Ron Meir,et al.  Tradeoffs and Constraints on Neural Representation in Networks of Cortical Neurons , 2010, The Journal of Neuroscience.

[30]  O. Jensen,et al.  Shaping Functional Architecture by Oscillatory Alpha Activity: Gating by Inhibition , 2010, Front. Hum. Neurosci..

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

[32]  G. Buzsáki,et al.  Temporal Encoding of Place Sequences by Hippocampal Cell Assemblies , 2006, Neuron.

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

[34]  Erwan Dupont,et al.  Rapid developmental switch in the mechanisms driving early cortical columnar networks , 2006, Nature.

[35]  Steve M. Potter,et al.  Spatio-temporal electrical stimuli shape behavior of an embodied cortical network in a goal-directed learning task , 2008, Journal of neural engineering.

[36]  P. Jonas,et al.  Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks , 2007, Nature Reviews Neuroscience.

[37]  D. Prince,et al.  Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  H. Koch,et al.  Prostaglandin E2-Induced Synaptic Plasticity in Neocortical Networks of Organotypic Slice Cultures , 2010, The Journal of Neuroscience.

[39]  R. Khazipov,et al.  GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. , 2007, Physiological reviews.

[40]  B. Connors,et al.  Two types of network oscillations in neocortex mediated by distinct glutamate receptor subtypes and neuronal populations. , 1996, Journal of neurophysiology.

[41]  M. Heuschkel,et al.  The generation of rhythmic activity in dissociated cultures of rat spinal cord , 2001, The European journal of neuroscience.

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

[43]  Michel A. Picardo,et al.  GABAergic Hub Neurons Orchestrate Synchrony in Developing Hippocampal Networks , 2009, Science.

[44]  D. Plenz,et al.  Generation of high-frequency oscillations in local circuits of rat somatosensory cortex cultures. , 1996, Journal of neurophysiology.

[45]  H. Robinson,et al.  Propagation of spontaneous synchronized activity in cortical slice cultures recorded by planar electrode arrays. , 2000, Bioelectrochemistry.

[46]  P. Renaud,et al.  Spatiotemporal characterization of rhythmic activity in rat spinal cord slice cultures , 2001, The European journal of neuroscience.

[47]  B. Connors,et al.  Initiation, Propagation, and Termination of Epileptiform Activity in Rodent Neocortex In Vitro Involve Distinct Mechanisms , 2005, The Journal of Neuroscience.

[48]  J. Sleigh,et al.  Excitatory effects of gap junction blockers on cerebral cortex seizure‐like activity in rats and mice , 2009, Epilepsia.

[49]  Alison L. Barth,et al.  An Embedded Subnetwork of Highly Active Neurons in the Neocortex , 2010, Neuron.

[50]  D. McCormick,et al.  Endogenous Electric Fields May Guide Neocortical Network Activity , 2010, Neuron.

[51]  T. Sejnowski,et al.  Thalamocortical oscillations in the sleeping and aroused brain. , 1993, Science.

[52]  Christof Koch,et al.  Ephaptic coupling of cortical neurons , 2011, Nature Neuroscience.

[53]  Jyh-Jang Sun,et al.  Three Patterns of Oscillatory Activity Differentially Synchronize Developing Neocortical Networks In Vivo , 2009, The Journal of Neuroscience.

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

[55]  György Buzsáki,et al.  Neural Syntax: Cell Assemblies, Synapsembles, and Readers , 2010, Neuron.

[56]  J. Bolz,et al.  Formation and preservation of cortical layers in slice cultures. , 1992, Journal of neurobiology.

[57]  B. Sakmann,et al.  Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches , 1981, Pflügers Archiv.

[58]  Pavlos Rigas,et al.  Synchronized oscillations caused by disinhibition in rodent neocortex are generated by recurrent synaptic activity mediated by AMPA receptors , 2002, The Journal of physiology.

[59]  T. Sejnowski,et al.  Origin of slow cortical oscillations in deafferented cortical slabs. , 2000, Cerebral cortex.

[60]  Jürg Streit,et al.  Patterns of spontaneous activity in unstructured and minimally structured spinal networks in culture , 2005, Experimental Brain Research.