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.

Application of Fitts' law to individuals with cerebral palsy.

Cerebral palsy is a condition that results in motor abnormalities as a direct consequence of injury to the developing brain. Fitts' law, which describes a speed-accuracy tradeoff in visually guided movements, has been shown to characterize the motor behavior of normal subjects during aiming tasks. To assess whether Fitts' law can also describe the aimed movements of persons with cerebral palsy, eight cerebral palsied adults participated in an aimed movement study. 12 targets were used with Indices of Difficulty ranging from 2.19 to 6.00 bits. The impact of Gan and Hoffmann's 1988 ballistic movement factor, square root(A) , and Fitts' 1954 Index of Difficulty on subject's movement and reaction times was examined using multivariate linear models. The analysis of the full data set yielded a significant effect of square root(A) on movement times and no significant adherence to Fitts' law. However, high error rates that could be the result of oculomotor problems among the subject group were noted, and the method of handling errors had a large effect on the results. Tracking eye position during a Fitts' law task would provide information regarding the effect of oculomotor difficulties on aiming tasks in the cerebral palsied subject group.