Postnatal alterations of the inhibitory synaptic responses recorded from cortical pyramidal neurons in the Lis1/sLis1 mutant mouse

Abstract

Mutations in the mouse Lis1 gene produce severe alterations in the developing cortex. We have examined some electrophysiological responses of cortical pyramidal neurons during the early postnatal development of Lis/sLis1 mutant mice. In P7 and P30 Lis1/sLis1 neurons we detected a lower frequency and slower decay phase of mIPSCs, and at P30 the mIPSCs amplitude and the action potential duration were reduced. Zolpidem (an agonist of GABA A receptors containing the α 1 subunit) neither modified the amplitude nor the decay time of mIPSCs at P7 in Lis1/sLis1 neurons, whereas it increased the decay time at P30. The levels of GABA A receptor α 1 subunit mRNA were reduced in the Lis1/sLis1 brain at P7 and P30, whereas reduced levels of the corresponding protein were only found at P7. These results demonstrate the presence of functional alterations in the postnatal Lis1/sLis1 cortex and point to abnormalities in GABA A receptor subunit switching processes during postnatal development.