Frontiers in Cellular Neuroscience (Jun 2014)

Altered GABAergic markers, increased binocularity and reduced plasticity in the visual cortex of Engrailed-2 knockout mice

  • Manuela eAllegra,
  • Manuela eAllegra,
  • Sacha eGenovesi,
  • Marika eMaggia,
  • Maria Cristina Cenni,
  • Giulia eZunino,
  • Paola eSgadò,
  • Matteo eCaleo,
  • Yuri eBozzi,
  • Yuri eBozzi

DOI
https://doi.org/10.3389/fncel.2014.00163
Journal volume & issue
Vol. 8

Abstract

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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.

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