title: Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks.
abstract: Epilepsy is characterized by impaired circuit function and a propensity for spontaneous seizures, but how plastic rearrangements within the epileptic focus trigger cortical dysfunction and hyperexcitability is only partly understood. Here we have examined alterations in sensory processing and the underlying biochemical and neuroanatomical changes in tetanus neurotoxin (TeNT)-induced focal epilepsy in mouse visual cortex. We documented persistent epileptiform electrographic discharges and upregulation of GABAergic markers at the completion of TeNT effects. We also found a significant remodeling of the dendritic arbors of pyramidal neurons, with increased dendritic length and branching, and overall reduction in spine density but significant preservation of mushroom, mature spines. Functionally, spontaneous neuronal discharge was increased, visual responses were less reliable, and electrophysiological and behavioural visual acuity was consistently impaired in TeNT-injected mice. These data demonstrate robust, long-term remodeling of both inhibitory and excitatory circuitry associated with specific disturbances of network function in neocortical epilepsy.
authors.affiliation: CNR Neuroscience Institute, via G. Moruzzi 1, 56124, Pisa, Italy.|Scuola Normale Superiore, Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vannini
authors.affiliation: CNR Neuroscience Institute, via G. Moruzzi 1, 56124, Pisa, Italy. restani@in.cnr.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Restani
authors.affiliation: CNR Neuroscience Institute, via G. Moruzzi 1, 56124, Pisa, Italy.|Scuola Normale Superiore, Pisa, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Pietrasanta
authors.affiliation: CNR Neuroscience Institute, via G. Moruzzi 1, 56124, Pisa, Italy.|The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Panarese
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mazzoni
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Rossetto
authors.affiliation: CNR Institute of Cell Biology and Neurobiology, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Middei
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.|Bertarelli Foundation Chair in Translational Neuroengineering, School of Engineering, Center for Neuroprosthetics and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Silvestro
authors.initials: S
authors.lastname: Micera
authors.affiliation: CNR Neuroscience Institute, via G. Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
mesh_terms: D000818:Animals; D003712:Dendrites / Q000473:pathology* / Q000502:physiology; D004828:Epilepsies, Partial / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005074:Evoked Potentials, Visual; D059330:GABAergic Neurons / Q000378:metabolism; D008666:Metalloendopeptidases; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D010775:Photic Stimulation; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology; D013744:Tetanus Toxin; D015854:Up-Regulation; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D014792:Visual Acuity; D014793:Visual Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D013744:Tetanus Toxin; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse; C035979:tetanospasmin; D005680:gamma-Aminobutyric Acid; D008666:Metalloendopeptidases
keywords: Dendritic spines; Epilepsy; Spontaneous activity; Tetanus neurotoxin; Visual acuity; Visual cortex