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

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 (En(2-/-)) mice show ASD-like features accompanied by a partial loss of cortical GABAergic interneurons. Here we studied GABAergic markers and cortical function in En(2-/-) 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 En(2+/+) controls, En(2-/-) 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 En(2+/+)and En(2-/-) mice were layer-specific. Adult En(2-/-) 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 En(2-/-) primary visual cortex. However, a significant increase of binocularity was found in P30 and adult En(2-/-) mice, as compared to age-matched controls. Differently from what observed in En(2+/+) mice, the En(2-/-) 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 En(2-/-) mice, while leaving other visual functional properties unaffected.