Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior.
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Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. / Peters, H Christian; Hu, Hua; Pongs, Olaf; Storm, Johan F; Isbrandt, Dirk.
in: NAT NEUROSCI, Jahrgang 8, Nr. 1, 1, 2005, S. 51-60.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior.
AU - Peters, H Christian
AU - Hu, Hua
AU - Pongs, Olaf
AU - Storm, Johan F
AU - Isbrandt, Dirk
PY - 2005
Y1 - 2005
N2 - In humans, mutations in the KCNQ2 or KCNQ3 potassium-channel genes are associated with an inherited epilepsy syndrome. We have studied the contribution of KCNQ/M-channels to the control of neuronal excitability by using transgenic mice that conditionally express dominant-negative KCNQ2 subunits in brain. We show that suppression of the neuronal M current in mice is associated with spontaneous seizures, behavioral hyperactivity and morphological changes in the hippocampus. Restriction of transgene expression to defined developmental periods revealed that M-channel activity is critical to the development of normal hippocampal morphology during the first postnatal weeks. Suppression of the M current after this critical period resulted in mice with signs of increased neuronal excitability and deficits in hippocampus-dependent spatial memory. M-current-deficient hippocampal CA1 pyramidal neurons showed increased excitability, reduced spike-frequency adaptation, attenuated medium afterhyperpolarization and reduced intrinsic subthreshold theta resonance. M channels are thus critical determinants of cellular and neuronal network excitability, postnatal brain development and cognitive performance.
AB - In humans, mutations in the KCNQ2 or KCNQ3 potassium-channel genes are associated with an inherited epilepsy syndrome. We have studied the contribution of KCNQ/M-channels to the control of neuronal excitability by using transgenic mice that conditionally express dominant-negative KCNQ2 subunits in brain. We show that suppression of the neuronal M current in mice is associated with spontaneous seizures, behavioral hyperactivity and morphological changes in the hippocampus. Restriction of transgene expression to defined developmental periods revealed that M-channel activity is critical to the development of normal hippocampal morphology during the first postnatal weeks. Suppression of the M current after this critical period resulted in mice with signs of increased neuronal excitability and deficits in hippocampus-dependent spatial memory. M-current-deficient hippocampal CA1 pyramidal neurons showed increased excitability, reduced spike-frequency adaptation, attenuated medium afterhyperpolarization and reduced intrinsic subthreshold theta resonance. M channels are thus critical determinants of cellular and neuronal network excitability, postnatal brain development and cognitive performance.
M3 - SCORING: Zeitschriftenaufsatz
VL - 8
SP - 51
EP - 60
JO - NAT NEUROSCI
JF - NAT NEUROSCI
SN - 1097-6256
IS - 1
M1 - 1
ER -
