Compensation by reduced L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses in a mouse model with reduced gamma-aminobutyric acid type A receptor-mediated synaptic inhibition.
L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists increase the threshold for electroshock-induced convulsions. Here, we show that a transgenic mouse line overexpressing cerebellum-restricted gamma-aminobutyric acid type A (GABA(A)) receptor alpha6 subunit in the hippocampal CA1 pyramidal cells (Thy1alpha6 mouse line) exhibits about a 20% increase in the electroshock current intensity inducing tonic hindlimb extension convulsion in 50% of the mice compared with that of their wild-type controls. AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in patch clamp recordings of CA1 pyramidal neurons in hippocampal slices had decreased amplitudes (8.4 +/- 2.2 pA) in the transgenics compared with the wild types (10.3 +/- 2.5 pA) but showed no change in current decay or frequency. Our results suggest that decreased AMPA-mediated neurotransmission might explain the increased threshold for electroconvulsions and warrant further studies on the regulation between various components of inhibition and excitation in neurons.
Möykkynen
Tommi P
TP
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. tommi.moykkynen@helsinki.fi
Sinkkonen
Saku T
ST
Korpi
Esa R
ER
D000818:Animals; D004594:Electrophysiology; D004597:Electroshock; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D023421:Models, Animal; D017966:Pyramidal Cells / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*
D018091:Receptors, AMPA; D011963:Receptors, GABA-A