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Brain Structure and Function

, Volume 221, Issue 6, pp 2919–2936 | Cite as

Altered sensory processing and dendritic remodeling in hyperexcitable visual cortical networks

  • Eleonora Vannini
  • Laura Restani
  • Marta Pietrasanta
  • Alessandro Panarese
  • Alberto Mazzoni
  • Ornella Rossetto
  • Silvia Middei
  • Silvestro Micera
  • Matteo Caleo
Original Article

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.

Keywords

Tetanus neurotoxin Visual cortex Dendritic spines Spontaneous activity Visual acuity Epilepsy 

Notes

Acknowledgments

The authors thank Francesca Biondi for invaluable technical support. This work was supported by a grant from Fondazione Pisa (to M.C.) and by Italian Ministry of Research (FIRB2010-RBFR10ZBYZ_003) to L.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

429_2015_1080_MOESM1_ESM.pdf (4.4 mb)
Supplementary Figure 1. Characterization of TeNT effects in visual cortex. (a) Representative immunoblotting for cleaved (top) and intact VAMP2 (middle) on protein extracts from the visual cortex. N, cortex from a naïve uninjected mouse; numbers indicate days after TeNT injection. α-tubulin (α-tub) is used as an internal standard for protein quantification. (b) Representative immunostaining for the neuronal marker NeuN in vehicle (Veh; left) and TeNT-injected mice (right). No neuronal loss is evident. Scale bar = 50 µm. (c) Representative local field potential recordings from the visual cortex of freely moving mice: two representative TeNT-infused animals, either 10 days (middle) or 45 days (right) after toxin delivery. The bottom traces are 6 sec epochs recorded from a TeNT-injected mouse at 45 days, and shown on an enlarged scale to better discern single interictal and ictal events (DOCX 15 kb) (PDF 4530 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Eleonora Vannini
    • 1
    • 2
  • Laura Restani
    • 1
  • Marta Pietrasanta
    • 1
    • 2
  • Alessandro Panarese
    • 1
    • 3
  • Alberto Mazzoni
    • 3
  • Ornella Rossetto
    • 4
  • Silvia Middei
    • 5
  • Silvestro Micera
    • 3
    • 6
  • Matteo Caleo
    • 1
  1. 1.CNR Neuroscience InstitutePisaItaly
  2. 2.Scuola Normale SuperiorePisaItaly
  3. 3.The BioRobotics InstituteScuola Superiore Sant’AnnaPisaItaly
  4. 4.Department of Biomedical SciencesUniversity of PaduaPaduaItaly
  5. 5.CNR Institute of Cell Biology and NeurobiologyRomeItaly
  6. 6.Bertarelli Foundation Chair in Translational Neuroengineering, School of Engineering, Center for Neuroprosthetics and Institute of BioengineeringÉcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland

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