|
Effects of subtype-specific loss of inhibitory interneurons on receptive field properties in visual cortex
*R. MAO1,2, J. SCHUMMERS1,2, A. VAN WART1,2, B. CRONIN1,2, G. PRUSKY3,4, N. ALAM3,4, C. KIM5, J. L. R. RUBENSTEIN5, M. SUR1,2;
|
|
Inhibitory interneurons are vital to cortical development and function. These cells comprise 20-30% of neocortical neurons, and exhibit great diversity in morphological, physiological, molecular and synaptic characteristics. Given the diversity in their properties, it is probable that different classes of interneurons have distinct roles in modulating integrative responses and receptive field properties in the visual cortex. The Dlx homeobox transcription factor family regulates the development of inhibitory interneurons. To probe the function of these interneuron classes, we utilized a Dlx1-/- mouse line (Cobos et al., Nat Neurosci 2005) that shows a specific loss of cortical and hippocampal calretinin- and somatostatin-expressing subclasses in early adulthood but no discernible effect on the parvalbumin-expressing subclass. Calretinin and somatostatin are expressed in double bouquet, bipolar, bitufted and Martinotti cells (which target dendrites and apical tufts), whereas Parvalbumin is expressed in basket cells (which target somata and proximal dendrites) and chandelier cells (which target axon initial segments). Immunohistochemistry on Dlx1-/- mice showed a partial reduction (33.6 ± 1.3%) of calretinin-positive neurons in visual cortex at postnatal day 60+ compared to wild types. 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, there appeared to be fewer tuned cells and significantly broadened orientation tuning in Dlx1-/- mice (n>100 cells) than in wild types (n>50 cells) based on single-unit recording experiments in adult V1. This effect is specific, as intrinsic signal optical imaging maps of retinotopy and ocular dominance were unchanged in adult Dlx1-/- mice. Visual cliff tests, visual water maze tests and threshold tests of optokinetic tracking on Dlx1-/- mice did not detect overt deficits in vision. Our findings reveal a key role for this dendritic-targeting class of inhibitory interneurons in the fine tuning of stimulus-specific visual responses.
|