Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability

Raffaella Tonini, Silvana Franceschetti, Daniela Parolaro, Mariaelvina Sala, Enzo Mancinelli, Silvia Tininini, Ronny Brusetti, Giulio Sancini, Riccardo Brambilla, Enzo Martegani, Emmapaola Sturani, Renata Zippel

Research output: Contribution to journalArticlepeer-review


Ras-GRF1 is a neuron-specific guanine nucleotide exchange factor for Ras proteins. Mice lacking Ras-GRF1 (-/-) are severely impaired in amygdala-dependent long-term synaptic plasticity and show higher basal synaptic activity at both amygdala and hippocampal synapses (Brambilla et al., 1997). In the present study we investigated the effects of Ras-GRF1 deletion on hippocampal neuronal excitability. Electrophysiological analysis of both primary cultured neurons and adult hippocampal slices indicated that Ras-GRF1-/- mice displayed neuronal hyperexcitability. Ras-GRF1-/- hippocampal neurons showed increased spontaneous activity and depolarized resting membrane potential, together with a higher firing rate in response to injected current. Changes in the intrinsic excitability of Ras-GRF1-/- neurons can entail these phenomena, suggesting that Ras-GRF1 deficiency might alter the balance between ionic conductances. In addition, we showed that mice lacking Ras-GRF1 displayed a higher seizure susceptibility following acute administration of convulsant drugs. Taken together, these results demonstrated a role for Ras-GRF1 in neuronal excitability.

Original languageEnglish
Pages (from-to)691-701
Number of pages11
JournalMolecular and Cellular Neuroscience
Issue number6
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience


Dive into the research topics of 'Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability'. Together they form a unique fingerprint.

Cite this