title: Altered GABAergic markers, increased binocularity and reduced plasticity in the visual cortex of Engrailed-2 knockout mice.
abstract: The maturation of the GABAergic system is a crucial determinant of cortical development during early postnatal life, when sensory circuits undergo a process of activity-dependent refinement. An altered excitatory/inhibitory balance has been proposed as a possible pathogenic mechanism of autism spectrum disorders (ASD). The homeobox-containing transcription factor Engrailed-2 (En2) has been associated to ASD, and En2 knockout (En2 (-/-)) mice show ASD-like features accompanied by a partial loss of cortical GABAergic interneurons. Here we studied GABAergic markers and cortical function in En2 (-/-) mice, by exploiting the well-known anatomical and functional features of the mouse visual system. En2 is expressed in the visual cortex at postnatal day 30 and during adulthood. When compared to age-matched En2 (+/+) controls, En2 (-/-) mice showed an increased number of parvalbumin (PV(+)), somatostatin (SOM(+)), and neuropeptide Y (NPY(+)) positive interneurons in the visual cortex at P30, and a decreased number of SOM(+) and NPY(+) interneurons in the adult. At both ages, the differences in distinct interneuron populations observed between En2 (+/+) and En2 (-/-) mice were layer-specific. Adult En2 (-/-) mice displayed a normal eye-specific segregation in the retino-geniculate pathway, and in vivo electrophysiological recordings showed a normal development of basic functional properties (acuity, response latency, receptive field size) of the En2 (-/-) primary visual cortex. However, a significant increase of binocularity was found in P30 and adult En2 (-/-) mice, as compared to age-matched controls. Differently from what observed in En2 (+/+) mice, the En2 (-/-) primary visual cortex did not respond to a brief monocular deprivation performed between P26 and P29, during the so-called "critical period." These data suggest that altered GABAergic circuits impact baseline binocularity and plasticity in En2 (-/-) mice, while leaving other visual functional properties unaffected.
authors.affiliation: Neuroscience Institute, National Research Council (CNR) Pisa, Italy ; Laboratory of Neurobiology, Scuola Normale Superiore Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Allegra
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento Mattarello, Trento, Italy.
authors.forename: Sacha
authors.initials: S
authors.lastname: Genovesi
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento Mattarello, Trento, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Maggia
authors.affiliation: Neuroscience Institute, National Research Council (CNR) Pisa, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cenni
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento Mattarello, Trento, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Zunino
authors.affiliation: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento Mattarello, Trento, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sgadò
authors.affiliation: Neuroscience Institute, National Research Council (CNR) Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
authors.affiliation: Neuroscience Institute, National Research Council (CNR) Pisa, Italy ; Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento Mattarello, Trento, Italy.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Bozzi
keywords: critical period; inhibition; monocular deprivation; neurodevelopmental disorder; plasticity