Abstract
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 language | English |
|---|---|
| Pages (from-to) | 691-701 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Neuroscience |
| Volume | 18 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2001 |
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ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Developmental Neuroscience
Cite this
Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability. / Tonini, Raffaella; Franceschetti, Silvana; Parolaro, Daniela; Sala, Mariaelvina; Mancinelli, Enzo; Tininini, Silvia; Brusetti, Ronny; Sancini, Giulio; Brambilla, Riccardo; Martegani, Enzo; Sturani, Emmapaola; Zippel, Renata.
In: Molecular and Cellular Neuroscience, Vol. 18, No. 6, 2001, p. 691-701.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability
AU - Tonini, Raffaella
AU - Franceschetti, Silvana
AU - Parolaro, Daniela
AU - Sala, Mariaelvina
AU - Mancinelli, Enzo
AU - Tininini, Silvia
AU - Brusetti, Ronny
AU - Sancini, Giulio
AU - Brambilla, Riccardo
AU - Martegani, Enzo
AU - Sturani, Emmapaola
AU - Zippel, Renata
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035681050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035681050&partnerID=8YFLogxK
U2 - 10.1006/mcne.2001.1050
DO - 10.1006/mcne.2001.1050
M3 - Article
C2 - 11749043
AN - SCOPUS:0035681050
VL - 18
SP - 691
EP - 701
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 6
ER -