title: Morphological organization of somatosensory cortex in Otx1(-/-) mice.
abstract: Knock-out Otx1 mice show brain hypoplasia, spontaneous epileptic seizures and abnormalities of the dorsal region of the neocortex. We investigated structural alterations in excitatory and inhibitory circuits in somatosensory cortex of Otx1(-/-) mice by immunocytochemistry using light, confocal and electron microscopy. Immunostaining for non-phosphorylated neurofilament SMI311 and subunit 1 of the NMDA receptor - used as markers of pyramidal neurons - showed reduced layer V pyramidal cells and ectopic pyramidal cells in layers II and III of the mutant cortex. Immunostaining for calcium-binding proteins calbindin, calretinin and parvalbumin - markers of non-overlapping types of GABAergic interneurons - showed no differences between wild-type and knock-out cortex for calbindin and calretinin neurons, while parvalbumin neurons were only patchily distributed in Otx1(-/-) cortex. The pattern of positivity of the GABAergic marker glutamic acid decarboxylase in Otx1(-/-) cortex was also altered and similar to that of parvalbumin. GABA transporter 1 immunoreactivity was greater in Otx1(-/-) than wild-type; quantitation of structures immunoreactive for this transporter in layer V showed that they were increased overall in Otx1(-/-) but the density of inhibitory terminals on pyramidal neurons in the same layer labeled with this transporter was similar to that in wild-type mice. No differences in the distribution or intensity of the glial markers GABA transporter 3 or glial fibrillary acidic protein were found. The defects found in the cortical GABAergic system of the Otx1(-/-) mouse can plausibly explain the cortical hyperexcitability that produces seizures in these animals.
authors.affiliation: Dipartimento Neurofisiologia Sperimentale, Istituto Nazionale Neurologico 'C Besta', via Celoria 11, 20133, Milano, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Cipelletti
authors.forename: G
authors.initials: G
authors.lastname: Avanzini
authors.forename: L
authors.initials: L
authors.lastname: Vitellaro-Zuccarello
authors.forename: S
authors.initials: S
authors.lastname: Franceschetti
authors.forename: G
authors.initials: G
authors.lastname: Sancini
authors.forename: T
authors.initials: T
authors.lastname: Lavazza
authors.forename: D
authors.initials: D
authors.lastname: Acampora
authors.forename: A
authors.initials: A
authors.lastname: Simeone
authors.forename: R
authors.initials: R
authors.lastname: Spreafico
authors.forename: C
authors.initials: C
authors.lastname: Frassoni
mesh_terms: D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050485:GABA Plasma Membrane Transport Proteins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000002:abnormalities* / Q000378:metabolism* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D027361:Organic Anion Transporters; D051857:Otx Transcription Factors; D010320:Parvalbumins / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013003:Somatosensory Cortex / Q000002:abnormalities* / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D005968:Glutamate Decarboxylase; D018398:Homeodomain Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D016900:Neurofilament Proteins; D027361:Organic Anion Transporters; D051857:Otx Transcription Factors; D010320:Parvalbumins; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C497656:Otx1 protein, mouse; C402565:glutamate decarboxylase 1