Network stability through homeostatic scaling of excitatory and inhibitory synapses following inactivity in CA3 of rat organotypic hippocampal slice cultures

Homeostatic plasticity is a phenomenon whereby synaptic strength is scaled in the context of the activity that the network receives. Here, we have analysed excitatory and inhibitory synapses in a model of homeostatic plasticity where rat organotypic hippocampal slice cultures were deprived of excitatory synaptic input by the NMDA and AMPA/KA glutamate receptor antagonists, AP5 and CNQX. We show that chronic excitatory synapse deprivation generates an excitable CA3 network where enhanced amplitude and frequency of spontaneous excitatory post-synaptic potentials were associated with increased glutamate receptor subunit expression and increased number and size of synapsin 1 and VGLUT1 positive puncta. Intact spontaneous inhibitory post-synaptic potentials coincided with persistent expression of the GABA-A receptor alpha subunit and GAD65 and an enhancement of parvalbumin-positive puncta. In this model of homeostatic plasticity, scaling up of synaptic excitation and maintenance of fast synaptic inhibition promote an excitable, but stable, CA3 network.

[1]  Christian Rosenmund,et al.  An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Nelson,et al.  Hebb and homeostasis in neuronal plasticity , 2000, Current Opinion in Neurobiology.

[3]  M. V. Rossum,et al.  Activity Coregulates Quantal AMPA and NMDA Currents at Neocortical Synapses , 2000, Neuron.

[4]  P. E. Kunkler,et al.  Homeostatic plasticity in hippocampal slice cultures involves changes in voltage-gated Na+ channel expression , 2004, Brain Research.

[5]  G. Turrigiano,et al.  Postsynaptic Expression of Homeostatic Plasticity at Neocortical Synapses , 2005, The Journal of Neuroscience.

[6]  Sacha B. Nelson,et al.  Activity-dependent regulation of excitability in rat visual cortical neurons , 1999, Neurocomputing.

[7]  M. Farrant,et al.  CNQX increases GABA-mediated synaptic transmission in the cerebellum by an AMPA/kainate receptor-independent mechanism , 2001, Neuropharmacology.

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

[9]  H. Okado,et al.  Continual remodeling of postsynaptic density and its regulation by synaptic activity , 1999, Nature Neuroscience.

[10]  Nathan R. Wilson,et al.  Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1 , 2005, The Journal of Neuroscience.

[11]  C. Shatz,et al.  Developmental mechanisms that generate precise patterns of neuronal connectivity , 1993, Cell.

[12]  Ann Marie Craig,et al.  Synapse composition and organization following chronic activity blockade in cultured hippocampal neurons , 2005, The Journal of comparative neurology.

[13]  A. Habets,et al.  Development in the absence of spontaneous bioelectric activity results in increased stereotyped burst firing in cultures of dissociated cerebral cortex , 2004, Experimental Brain Research.

[14]  C. Goodman,et al.  Synapse-specific control of synaptic efficacy at the terminals of a single neuron , 1998, Nature.

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

[16]  V. Murthy,et al.  Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons , 2002, Nature.

[17]  W. Cannon.  The Wisdom of the Body , 1932 .

[18]  P. De Camilli,et al.  Chronic Blockade of Glutamate Receptors Enhances Presynaptic Release and Downregulates the Interaction between Synaptophysin-Synaptobrevin–Vesicle-Associated Membrane Protein 2 , 2001, The Journal of Neuroscience.

[19]  Ann Marie Craig,et al.  Activity Regulates the Synaptic Localization of the NMDA Receptor in Hippocampal Neurons , 1997, Neuron.

[20]  G. Mealing,et al.  A fluorescence confocal assay to assess neuronal viability in brain slices. , 1998, Brain research. Brain research protocols.

[21]  M. Stryker,et al.  Distributions of synaptic vesicle proteins and GAD65 in deprived and nondeprived ocular dominance columns in layer IV of kitten primary visual cortex are unaffected by monocular deprivation , 2000, The Journal of comparative neurology.

[22]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[23]  D. Potter,et al.  Seizure-like activity and cellular damage in rat hippocampal neurons in cell culture , 1989, Neuron.

[24]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[25]  G. Davis,et al.  Maintaining the stability of neural function: a homeostatic hypothesis. , 2001, Annual review of physiology.

[26]  T. Schikorski,et al.  Inactivity Produces Increases in Neurotransmitter Release and Synapse Size , 2001, Neuron.

[27]  R. Empson,et al.  Comparison of neuroplastin and synaptic marker protein expression in acute and cultured organotypic hippocampal slices from rat. , 2004, Brain research. Developmental brain research.

[28]  N. Syed,et al.  Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together , 2003, The Journal of physiology.

[29]  R. Huganir,et al.  Activity-Dependent Modulation of Synaptic AMPA Receptor Accumulation , 1998, Neuron.

[30]  K. Obrietan,et al.  Glutamate hyperexcitability and seizure-like activity throughout the brain and spinal cord upon relief from chronic glutamate receptor blockade in culture , 1996, Neuroscience.

[31]  P. Kostyuk,et al.  Chronic treatment with ionotropic glutamate receptor antagonist kynurenate affects GABAergic synaptic transmission in rat hippocampal cell cultures , 2003, Neuroscience Letters.

[32]  M. Schäfer,et al.  Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits , 2005, The Journal of Neuroscience.

[33]  Bing Li,et al.  Enhancement of Synaptic Plasticity through Chronically Reduced Ca2+ Flux during Uncorrelated Activity , 2004, Neuron.

[34]  V. Murthy,et al.  Synaptic gain control and homeostasis , 2003, Current Opinion in Neurobiology.

[35]  S. Royer,et al.  Conservation of total synaptic weight through balanced synaptic depression and potentiation , 2003, Nature.

[36]  R K Wong,et al.  Inhibitory control of local excitatory circuits in the guinea‐pig hippocampus. , 1987, The Journal of physiology.

[37]  G. Turrigiano.  Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same , 1999, Trends in Neurosciences.

[38]  G. Marrs,et al.  Hippocampal mossy fibers induce assembly and clustering of PSD95‐containing postsynaptic densities independent of glutamate receptor activation , 2001, The Journal of comparative neurology.

[39]  Mark C. W. van Rossum,et al.  Activity Deprivation Reduces Miniature IPSC Amplitude by Decreasing the Number of Postsynaptic GABAA Receptors Clustered at Neocortical Synapses , 2002, The Journal of Neuroscience.

[40]  J. Swann,et al.  Postsynaptic contributions to hippocampal network hyperexcitability induced by chronic activity blockade in vivo , 2003, The European journal of neuroscience.

[41]  D. Kullmann,et al.  Extrasynaptic glutamate spillover in the hippocampus: evidence and implications , 1998, Trends in Neurosciences.

[42]  R. Tsien,et al.  Adaptation to Synaptic Inactivity in Hippocampal Neurons , 2005, Neuron.