Inhibitory interneurons comprise 20-30% of neocortical neurons, but exhibit great diversity in morphological, physiological, molecular and synaptic characteristics. Parvalbumin, a calcium-binding protein, is expressed in basket cells (which target somata and proximal dendrites) and chandelier cells (which target axon initial segments). By contrast, calretinin, another calcium-binding protein, and neuropeptides such as somatostatin and NPY, are expressed in double bouquet cells, bipolar cells, bitufted cells and Martinotti cells (which target dendrites and apical tufts). Given the diversity in their properties, it is probable that different classes of inhibitory interneurons have distinct roles in modulating integrative responses and receptive field properties in the visual cortex. Dlx1 is a homeobox transcription factor expressed by specific interneurons in the adult cortex. To probe the function of these interneuron classes, we utilized a Dlx1-/- mouse line (Cobos et al., Nature Neuroscience 2005) that shows a specific loss of calretinin- and somatostatin/NPY-expressing subclasses in early adulthood but no discernible effect on the parvalbumin-expressing subclass. The knockout mice have reductions in both the amplitude and frequency of spontaneous IPSCs in cortex. Immunohistochemistry on the Dlx1-/- mice showed a partial reduction (33.6 ± 1.3%) of calretinin-positive neurons in visual cortex at postnatal day 60+ compared to wild type. Parvalbumin immunohistochemistry was unchanged in the knockout mice. Given previous evidence for a critical role of inhibition in sharpening orientation selectivity, we postulated that the interneuron deficit would result in a disruption of tuned responses in the primary visual cortex (V1). Consistent with this hypothesis, single-unit recordings in V1 of adult Dlx1-/- mice (n>100 cells) indicated fewer tuned cells and significantly broadened orientation tuning than in wild types (n>50 cells). Interestingly, there also appeared to be reduced visual response amplitude and spontaneous activity in the Dlx1-/- mice. Visual cliff tests and water maze tests on Dlx1-/- mice showed no overt deficits in vision, but finer alterations are possible and would require further behavioral study.

Supported by EY07023 and EY015068. RM is supported by NEI Kirschstein-NRSA Fellowship 1 F32 EY017243.