Neuron-glia signaling in brain function and dysfunction

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/it/people-it/115-gabriele-losi)

  People

Faculty

  • Piergiorgio CARMIGNOTO - C.N.R. Research Director
  • Gabriele LOSI - C.N.R. Researcher
  • Micaela ZONTA - C.N.R. technologist

Lab Members

  • Iacopo MARCON - PhD Student
  • Linda Maria REQUIE - PhD Student
  • Alessandra TESSARI - Freelance biologist
  • Angela CHIAVEGATO - Research assistant

  Five recent publications

  1. Lia A, Zonta M, Requie LM, Carmignoto G. Dynamic interactions between GABAergic and astrocytic networks. Neurosci Lett. 2019 Jan 10;689:14-20. doi: 10.1016/j.neulet.2018.06.026. Epub 2018 Jun 15. Review.
  2. Mariotti L, Losi G, Lia A, Melone M, Chiavegato A, Gómez-Gonzalo M, Sessolo M, Bovetti S, Forli A, Zonta M, Requie LM, Marcon I, Pugliese A, Viollet C, Bettler B, Fellin T, Conti F, Carmignoto G. Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes. Nature Communications. 2018 Jan 8;9(1):82. doi: 10.1038/s41467-017-02642-6. * equal contribution.
  3. Gómez-Gonzalo M, Zehnder T, Requie LM, Bezzi P, CarmignotoG. Insights into the release mechanism of astrocytic glutamate evoking in neurons NMDA receptor-mediated slow depolarizing inward currents. Glia. 2018 Oct;66(10):2188-2199. doi: 10.1002/glia.23473. Epub 2018 Aug 25.
  4. Sessolo M, Marcon I, Bovetti S, Losi G, Cammarota M, Ratto GM,Fellin T and Carmignoto G. Parvalbumin-positive inhibitory interneurons oppose propagation but favor generation of focal epileptiform activity. J Neuroscience, 2015 Jul 1;35(26):9544-57. doi: 10.1523/JNEUROSCI.5117-14.2015.
  5. Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A. Gliotransmitters travel in time and space. Neuron. 2014 Feb 19;81(4):728-39. doi: 10.1016/j.neuron.2014.02.007. Review

  Projects

  • CNR
  • Telethon
  • CARIPARO
  • EU Eranet BrIE