Compensation by reduced L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses in a mouse model with reduced γ-aminobutyric acid type A receptor-mediated synaptic inhibition

✍ Scribed by Tommi P. Möykkynen; Saku T. Sinkkonen; Esa R. Korpi

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 110 KB
• Volume: 85
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21138

✦ Synopsis

Abstract

L‐α‐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 γ‐aminobutyric acid type A (GABA~A~) receptor α6 subunit in the hippocampal CA1 pyramidal cells (Thy1α6 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. © 2006 Wiley‐Liss, Inc.