Neuron-glia Interaction and Epilepsy

Description

Accumulating evidence supports the presence of a direct role of the glial cells astrocytes in brain functions that were once considered an exclusive domain of neurons. By releasing gliotransmitters such as glutamate, ATP and D-serine, astrocytes can indeed modulate synaptic transmission and contribute to brain information processing in a dynamic interaction with neurons that is finely regulated in time and space. Their active role in neuronal excitability and network activities can also contribute to brain disorders such as Parkinson's disease, schizophrenia and epilepsy. Our studies showing the involvement of astrocytes in seizure generation in a brain slice model of focal epilepsy, hint at astrocytes as potential novel therapeutic targets for epilepsy (Losi et al 2010; Gomez-Gonzalo et al 2010). Our more recent data also show that the propagation of seizure-like discharges follows a dramatic collapse of inhibitory transmission which is mainly caused by an impairment of parvalbumin fast-spiking GABAergic interneuron activity (Cammarota et al. 2013). Activation of astrocytes by different GABAergic interneurons, including the Parvalbumin interneurons, may be involved in the control of seizures. By using optogenetic tools to selectively activate specific interneuron subpopulations in different models of epilepsy we are currently further investigating the astrocyte contribution in the cellular events that govern generation and propagation of epileptic seizures (see also: http://www.in.cnr.it/index.php/en/staff-padova-en/95-losi-en)

 

5 recent publications

  • Sessolo M*, Marcon I*, Bovetti S, Losi G, Cammarota M, Ratto GM, Fellin T and Carmignoto G. (2015) Parvalbumin-positive inhibitory interneurons oppose propagation but favor generation of focal epileptiform activity. J Neuroscience; in press. * equally contributed
  • Losi G., Mariotti L. and Carmignoto G. (2014) GABAergic interneuron to astrocyte signaling: a neglected form of cell communication in the brain. Phil. Trans. R. Soc. B369: 20130609 dx.doi.org/10.1098/rstb. 2013.0609.
  • Chiavegato A, Zurolo E, Losi G, Aronica E, Carmignoto G. (2014) The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy. Front Cell Neurosci. 6;8:155. doi: 10.3389/fncel.2014.00155.
  • Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A. (2014) Gliotransmitters travel in time and space. Neuron. 2014 Feb 19;81(4):728-39. doi: 10.1016/j.neuron.2014.02.007.
  • Cammarota M*, Losi G*, Chiavegato A, Zonta M, Carmignoto G. (2013) Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy. J Physiol. 591(Pt 4):807-22. * equally contributed.

 

Grants

  • CNR
  • Telethon
  • CARIPARO
  • EU Eranet BrIE