| First Author | Tonini R | Year | 2001 |
| Journal | Mol Cell Neurosci | Volume | 18 |
| Issue | 6 | Pages | 691-701 |
| PubMed ID | 11749043 | Mgi Jnum | J:73863 |
| Mgi Id | MGI:2156966 | Doi | 10.1006/mcne.2001.1050 |
| Citation | Tonini R, et al. (2001) Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability. Mol Cell Neurosci 18(6):691-701 |
| abstractText | 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. |
