Aberrant retinal projections in congenitally deaf mice: how are phenotypic characteristics specified in development and evolution?

The contribution of sensory input to the formation of sensory system-specific (sensoritopic) connections of the thalamus and midbrain was investigated using mice lacking the Na+-K+-2Cl- cotransporter (NKCC1) or the plasma membrane Ca2+-ATPase isoform2 (PMCA2). Because these mice are congenitally deaf, the developing nervous system has no exposure to sensory-driven neural activity from the auditory system. Here we compared the retinofugal pathway in normal and congenitally deaf mice using intraocular injections of neuroanatomical tracers into each eye, and relating tracer patterns to identified thalamic nuclei and superior colliculus layers. We demonstrate that loss of such activity results in aberrant projections of the retina into nonvisual auditory structures such as the medial geniculate nucleus and the intermediate layers of the superior colliculus. These findings indicate that activity from peripheral sensory receptor arrays is necessary not only for the refinement of developing connections within a unimodal structure, but for the establishment of sensoritopic or sensory-specific connections of unimodal and multimodal structures. We hypothesize that specification of such connections may occur through the modulation of spatial expression patterns of molecules known to be involved in the development of topography of connections between brain structures, such as the ephrins, via activity-dependent, CRE-mediated gene expression.