Cross-modal neuroplasticity in neonatally enucleated hamsters: structure, electrophysiology, and behavior

Potential auditory compensation in neonatally bilaterally enucleated Syrian hamsters was explored anatomically, electrophysiologically and behaviourally. Gross morphology of the visual cortex appeared normal and no obvious cytoarchitectural malformation was discerned. However, enucleation induced a signi®cant increase in the spontaneous ®ring rate of visual cortex cells. Further, auditory stimuli elicited ®eld potentials and single unit responses in the visual cortex of enucleated, but not normal, animals. About 63 % of the cells isolated in the visual cortex of 16 enucleated hamsters responded to at least one type of auditory stimulus. Most of the responses were less vigorous and less time-locked than those of auditory cortex cells, and thresholds were typically higher. Projection tracing with WGA±HRP disclosed reciprocal connections between the visual cortex and the dorsal lateral geniculate nucleus in both intact and enucleated animals. However, in the enucleated animals retrogradely labelled cells were also found in the inferior colliculus, the major midbrain auditory nucleus. Behaviourally determined auditory sensitivity across the hearing range did not differ between enucleated and intact hamsters. Minimum audible angle, as determined by a conditioned suppression task, ranged from around 17 to 22°, with no signi®cant difference between normal and enucleated animals. The two groups also did not differ with regard to the direction of their unconditioned head orientating response to intermittent noise. However, the enucleated animals showed a more vigorous response and were slower to habituate to the noise. These results show that bilateral enucleation of newborn hamsters results in auditory activation of visual targets, in addition to the typica

Smooth and Cardiac Muscle-selective Knock-out of Krüppel-like Factor 4 Causes Postnatal Death and Growth Retardation*

Krüppel-like factor 4 (Klf4) is a transcription factor involved in differentiation and proliferation in multiple tissues. We demonstrated previously that tamoxifen-induced deletion of the Klf4 gene in mice accelerated neointimal formation but delayed down-regulation of smooth muscle cell differentiation markers in carotid arteries following injury. To further determine the role of Klf4 in the cardiovascular system, we herein derived mice deficient for the Klf4 gene in smooth and cardiac muscle using the SM22α promoter (SM22α-CreKI+/Klf4loxP/loxP mice). SM22α-CreKI+/Klf4loxP/loxP mice were born at the expected Mendelian ratio, but they gradually died after birth. Although ∼40% of SM22α-CreKI+/Klf4loxP/loxP mice survived beyond postnatal day 28, they exhibited marked growth retardation. In wild-type mice, Klf4 was expressed in the heart from late embryonic development through adulthood, whereas it was not expressed in smooth muscle. No changes were observed in morphology or expression of smooth muscle cell differentiation markers in vessels of SM22α-CreKI+/Klf4loxP/loxP mice. Of interest, cardiac output was significantly decreased in SM22α-CreKI+/Klf4loxP/loxP mice, as determined by magnetic resonance imaging. Moreover, a lack of Klf4 in the heart resulted in the reduction in expression of multiple cardiac genes, including Gata4. In vivo chromatin immunoprecipitation assays on the heart revealed that Klf4 bound to the promoter region of the Gata4 gene. Results provide novel evidence that Klf4 plays a key role in late fetal and/or postnatal cardiac development