Impaired Electrical Signaling Disrupts Gamma Frequency Oscillations in Connexin 36-Deficient Mice

Neural processing occurs in parallel in distant cortical areas even for simple perceptual tasks. Associated cognitive binding is believed to occur through the interareal synchronization of rhythmic activity in the gamma (30-80 Hz) range. Such oscillations arise as an emergent property of the neuronal network and require conventional chemical neurotransmission. To test the potential role of gap junction-mediated electrical signaling in this network property, we generated mice lacking connexin 36, the major neuronal connexin. Here we show that the loss of this protein disrupts gamma frequency network oscillations in vitro but leaves high frequency (150 Hz) rhythms, which may involve gap junctions between principal cells (Schmitz et al., 2001), unaffected. Thus, specific connexins differentially deployed throughout cortical networks are likely to regulate different functional aspects of neuronal information processing in the mature brain.

[1]  G. Buzsáki,et al.  Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

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

[4]  Nancy Kopell,et al.  Multispikes and Synchronization in a Large Neural Network with Temporal Delays , 2000, Neural Computation.

[5]  J. Degen,et al.  The murine gap junction gene connexin36 is highly expressed in mouse retina and regulated during brain development , 1998, FEBS letters.

[6]  M. Wilson,et al.  Coordinated Interactions between Hippocampal Ripples and Cortical Spindles during Slow-Wave Sleep , 1998, Neuron.

[7]  B. Morris,et al.  In situ hybridization protocols for the Brain , 1994 .

[8]  R. Traub,et al.  Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro , 1998, Nature.

[9]  R. Traub,et al.  Axo-Axonal Coupling A Novel Mechanism for Ultrafast Neuronal Communication , 2001, Neuron.

[10]  M. Capecchi The new mouse genetics: altering the genome by gene targeting. , 1989, Trends in genetics : TIG.

[11]  R. Traub,et al.  On the Mechanism of the γ → β Frequency Shift in Neuronal Oscillations Induced in Rat Hippocampal Slices by Tetanic Stimulation , 1999, The Journal of Neuroscience.

[12]  P. Thuras,et al.  Prenatal viral infection causes alterations in nNOS expression in developing mouse brains , 2000, Neuroreport.

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

[14]  A. Beaudet,et al.  Neurotensin-induced bursting of cholinergic basal forebrain neurons promotes gamma and theta cortical activity together with waking and paradoxical sleep. , 2000, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  O. Smithies,et al.  Altering mice by homologous recombination using embryonic stem cells. , 1994, The Journal of biological chemistry.

[16]  Fiona E. N. LeBeau,et al.  Differential Expression of Synaptic and Nonsynaptic Mechanisms Underlying Stimulus-Induced Gamma Oscillations In Vitro , 2001, The Journal of Neuroscience.

[17]  Michael N. Shadlen,et al.  Synchrony Unbound A Critical Evaluation of the Temporal Binding Hypothesis , 1999, Neuron.

[18]  M. V. Bennett,et al.  Gap junctions as electrical synapses. , 1997, Journal of neurocytology.

[19]  R. Parenti,et al.  Expression of connexin36 mRNA in adult rodent brain , 2000, Neuroreport.

[20]  G. Buzsáki,et al.  High-frequency network oscillation in the hippocampus. , 1992, Science.

[21]  A. Beaudet,et al.  Neurotensin-Induced Bursting of Cholinergic Basal Forebrain Neurons Promotes γ and θ Cortical Activity Together with Waking and Paradoxical Sleep , 2000, The Journal of Neuroscience.

[22]  R. Traub,et al.  High-frequency population oscillations are predicted to occur in hippocampal pyramidal neuronal networks interconnected by axoaxonal gap junctions , 1999, Neuroscience.

[23]  N. Belluardo,et al.  Expression of Cx36 in mammalian neurons , 2000, Brain Research Reviews.

[24]  O. Paulsen,et al.  Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro , 1998, Nature.

[25]  G. Buzsáki,et al.  tFast Network Oscillations in the Hippocampal CA1 Region of the Behaving Rat , 1999, The Journal of Neuroscience.

[26]  N. Belluardo,et al.  Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons , 1998, The European journal of neuroscience.

[27]  Fiona E. N. LeBeau,et al.  A model of gamma‐frequency network oscillations induced in the rat CA3 region by carbachol in vitro , 2000, The European journal of neuroscience.

[28]  D. Feldmeyer,et al.  Connexin expression in electrically coupled postnatal rat brain neurons. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Barth,et al.  Spatiotemporal organization of fast (>200 Hz) electrical oscillations in rat Vibrissa/Barrel cortex. , 1999, Journal of neurophysiology.

[30]  P. Somogyi,et al.  Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons , 2000, Nature Neuroscience.

[31]  L. C. Katz,et al.  Neuronal coupling and uncoupling in the developing nervous system , 1995, Current Opinion in Neurobiology.

[32]  Frank Buchholz,et al.  A new logic for DNA engineering using recombination in Escherichia coli , 1998, Nature Genetics.

[33]  R. Traub,et al.  Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation , 1995, Nature.

[34]  Wolf Singer,et al.  Time as coding space? , 1999, Current Opinion in Neurobiology.