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 journalArticle

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 languageEnglish
Pages (from-to)691-701
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume18
Issue number6
DOIs
Publication statusPublished - 2001

Fingerprint

ras-GRF1
Neurons
Amygdala
Guanine Nucleotide Exchange Factors
Convulsants
ras Proteins
Neuronal Plasticity
Membrane Potentials
Synapses
Seizures

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 journalArticle

Tonini, R, Franceschetti, S, Parolaro, D, Sala, M, Mancinelli, E, Tininini, S, Brusetti, R, Sancini, G, Brambilla, R, Martegani, E, Sturani, E & Zippel, R 2001, 'Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability', Molecular and Cellular Neuroscience, vol. 18, no. 6, pp. 691-701. https://doi.org/10.1006/mcne.2001.1050
Tonini, Raffaella ; Franceschetti, Silvana ; Parolaro, Daniela ; Sala, Mariaelvina ; Mancinelli, Enzo ; Tininini, Silvia ; Brusetti, Ronny ; Sancini, Giulio ; Brambilla, Riccardo ; Martegani, Enzo ; Sturani, Emmapaola ; Zippel, Renata. / Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability. In: Molecular and Cellular Neuroscience. 2001 ; Vol. 18, No. 6. pp. 691-701.
@article{45980bc1b5ec4ad8920997672372991c,
title = "Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability",
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.",
author = "Raffaella Tonini and Silvana Franceschetti and Daniela Parolaro and Mariaelvina Sala and Enzo Mancinelli and Silvia Tininini and Ronny Brusetti and Giulio Sancini and Riccardo Brambilla and Enzo Martegani and Emmapaola Sturani and Renata Zippel",
year = "2001",
doi = "10.1006/mcne.2001.1050",
language = "English",
volume = "18",
pages = "691--701",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",
number = "6",

}

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 -