Postnatal alterations of the inhibitory synaptic responses recorded from cortical pyramidal neurons in the Lis1/sLis1 mutant mouse.
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 GABAA receptors containing the alpha1 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 GABAA receptor alpha1 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 GABAA receptor subunit switching processes during postnatal development.
Valdés-Sánchez
Lourdes
L
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Campus de San Juan, Apartado 18, San Juan, 03550 Alicante, Spain.
Escámez
Teresa
T
Echevarria
Diego
D
Ballesta
Juan J
JJ
Tabarés-Seisdedos
Rafael
R
Reiner
Orly
O
Martinez
Salvador
S
Geijo-Barrientos
Emilio
E
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D018755:GABA Agonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D017966:Pyramidal Cells / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000077334:Zolpidem
D018755:GABA Agonists; D008869:Microtubule-Associated Proteins; D011725:Pyridines; D000077334:Zolpidem; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse