Neuronal nicotinic acetylcholine receptors and autosomal dominant nocturnal frontal lobe epilepsy: a critical review

2001 ◽  
Vol 442 (5) ◽  
pp. 642-651 ◽  
Author(s):  
Bernd Sutor ◽  
Gerd Zolles
Keyword(s):  
Frontal Lobe ◽  
Nicotinic Acetylcholine Receptors ◽  
Critical Review ◽  
Acetylcholine Receptors ◽  
Autosomal Dominant ◽  
Frontal Lobe Epilepsy ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Nocturnal Frontal Lobe Epilepsy

scholarly journals Is Too Much Inhibition to Blame in Autosomal Dominant Nocturnal Frontal Lobe Epilepsy?

2007 ◽  
Vol 7 (4) ◽  
pp. 114-116
Author(s):  
Gregory C. Mathews
Keyword(s):  
Frontal Lobe ◽  
Nicotinic Acetylcholine Receptors ◽  
Autosomal Dominant ◽  
Pyramidal Cells ◽  
Mutant Mice ◽  
Epilepsy Syndrome ◽  
Frontal Lobe Epilepsy ◽  
Nicotinic Acetylcholine ◽  
Nocturnal Frontal Lobe Epilepsy ◽  
Postsynaptic Currents

Seizures and Enhanced Cortical GABAergic Inhibition in Two Mouse Models of Human Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Klaassen A, Glykys J, Maguire J, Labarca C, Mody I, Boulter J. Proc Natl Acad Sci USA 2006;103(50):19152–19157. Selected mutations in the human α4 or β2 neuronal nicotinic acetylcholine receptor subunit genes cosegregate with a partial epilepsy syndrome known as autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To examine possible mechanisms underlying this inherited epilepsy, we engineered two ADNFLE mutations ( Chrna4S252F and Chrna4+L264) in mice. Heterozygous ADNFLE mutant mice show persistent, abnormal cortical electroencephalograms with prominent delta and theta frequencies, exhibit frequent spontaneous seizures, and show an increased sensitivity to the proconvulsant action of nicotine. Relative to WT, electrophysiological recordings from ADNFLE mouse layer II/III cortical pyramidal cells reveal a >20-fold increase in nicotine-evoked inhibitory postsynaptic currents with no effect on excitatory postsynaptic currents. i.p. injection of a subthreshold dose of picrotoxin, a use-dependent γ-aminobutyric acid receptor antagonist, reduces cortical electroencephalogram delta power and transiently inhibits spontaneous seizure activity in ADNFLE mutant mice. Our studies suggest that the mechanism underlying ADNFLE seizures may involve inhibitory synchronization of cortical networks via activation of mutant α4-containing nicotinic acetylcholine receptors located on the presynaptic terminals and somatodendritic compartments of cortical GABAergic interneurons.

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