Faculty Bibliography

Accuracy of shifting movements between two notes was examined in nine cellists (intermediate-professional skill levels). Three pairs of notes separated by different distances were tested under the same movement rate. Finger position on the string was measured by a circuit. Angular velocities of the left upper arm and forearm were measured by two angular velocity sensors; thus elbow angular velocity during shifts was estimated. Results showed that with increased elbow velocity and shifting distance endpoint variability stayed constant. The force of gravity assisted elbow extension during shifts toward higher pitched notes compared to flexion towards lower pitched notes, but faster movement velocity did not result in increased landing variability. Performance for note E on the A string was found to be less variable than other notes, suggesting that physical cue from the cello body geometry was used as a landmark for finger position. Cutaneous feedback from the thumb when hitting the body-neck junction enabled faster elbow extension velocity compared to shifts towards other notes. Cellists who showed higher performance accuracy also showed higher perceptual ability and performance proficiency. These results suggest that long-term over-training of fast and accurate movements enables musicians to maintain accuracy and variability across different movement distances and velocities. Higher perceptual ability and performance proficiency are correlated with increased accuracy but not lower variability, indicating although perceptual ability and performance proficiency are important for pitch accuracy, movement variability is still constrained by the capacity of the motor system, which is highly fine-tuned and different than non-musicians.

One of the earliest steps of embryonic development is the establishment of polarity along the anteroposterior axis. Extensive studies of Drosophila embryonic development have elucidated mechanisms for establishing polarity, while studies with other model systems have found that many of these molecular components are conserved through evolution. One exception is Bicoid, the master organizer of anterior development in Drosophila and higher dipterans, which is not conserved. Thus, the study of anteroposterior patterning in insects that lack Bicoid can provide insight into the evolution of the diversity of body plan patterning networks. To this end, we have established the long germ parasitic wasp Nasonia vitripennis as a model for comparative studies with Drosophila. Here we report that, in Nasonia, a gradient of localized caudal mRNA directs posterior patterning, whereas, in Drosophila, the gradient of maternal Caudal protein is established through translational repression by Bicoid of homogeneous caudal mRNA. Loss of caudal function in Nasonia results in severe segmentation defects. We show that Nasonia caudal is an activator of gap gene expression that acts far towards the anterior of the embryo, placing it atop a cascade of early patterning. By contrast, activation of gap genes in flies relies on redundant functions of Bicoid and Caudal, leading to a lack of dramatic action on gap gene expression: caudal instead plays a limited role as an activator of pair-rule gene expression. These studies, together with studies in short germ insects, suggest that caudal is an ancestral master organizer of patterning, and that its role has been reduced in higher dipterans such as Drosophila.

Sonic hedgehog has received an enormous amount of attention since its role as a morphogen that directs ventral patterning in the spinal cord was discovered a decade ago. Since that time, a bewildering array of information has been generated concerning both the components of the hedgehog signalling pathway and the remarkable number of contexts in which it functions. Nowhere is this more evident than in the nervous system, where hedgehog signalling has been implicated in events as disparate as axonal guidance and stem cell maintenance. Here we review our present knowledge of the hedgehog signalling pathway and speculate about areas in which further insights into this versatile pathway might be forthcoming

Neuregulins comprise a family of epidermal growth factor-like ligands that interact with ErbB receptor tyrosine kinases to control many aspects of neural development. One of the most dramatic effects of neuregulin-1 is on glial cell differentiation. The membrane-bound neuregulin-1 type III isoform is an axonal ligand for glial ErbB receptors that regulates the early Schwann cell lineage, including the generation of precursors. Recent studies have shown that the amount of neuregulin-1 type III expressed on axons also dictates the glial phenotype, with a threshold level triggering Schwann cell myelination. Remarkably, neuregulin-1 type III also regulates Schwann cell membrane growth to adjust myelin sheath thickness to match axon caliber precisely. Whether this signaling system operates in central nervous system myelination remains an open question of major importance for human demyelinating diseases

Recent advances in molecular genetics have produced many novel strategies for directing the expression of both functional and regulatory elements in transgenic mice. With the application of such approaches, the specific populations that comprise CNS networks can be both visualized and manipulated. Transgenic methods now range from the use of specific enhancer elements and large genomic regions assembled using BACs and PACs, to the use of gene targeting to a specific locus. In addition, the advent of transactivators and site-specific recombinases has provided unprecedented spatial and temporal control for directing expression in the CNS using a combination of appropriate alleles. As a result, the promise of being able to use transgenics to target specific neuronal populations is now being realized

BACKGROUND: Maturation of prefrontal circuits during adolescence contributes to the development of cognitive processes such as decision-making. Recent theories suggest that these neural changes also play a role in the shift from generalized anxiety disorder (GAD) to depression that often occurs during this developmental period. Cognitive models of the development of GAD highlight the role of intolerance of uncertainty (IU), which can be characterized behaviorally by impairments in decision-making. The present study examines potential developmental differences in frontal regions associated with uncertain decision-making, and tests the impact of IU on these circuits. METHODS: Twelve healthy adults (ages 19-36) and 12 healthy adolescents (ages 13-17) completed a decision-making task with conditions of varied uncertainty while fMRI scans were acquired. They also completed measures of worry and IU, and a questionnaire about their levels of anxiety and certainty during the task. RESULTS: Combined group analyses demonstrated significant linear effects of uncertainty on activity within anterior cingulate cortex (ACC). Region of interest (ROI)-based analysis found a significant interaction of group and IU ratings in ACC. Increased IU was associated with robust linear increases in ACC activity only in adolescents. An ROI analysis of feedback-related processing found that adolescents demonstrated greater activation during incorrect trials relative to correct trials, while the adults showed no difference in neural activity associated with incorrect and correct feedback. CONCLUSIONS: This decision-making task was shown to be effective at eliciting uncertainty-related ACC activity in adults and adolescents. Further, IU impacts ACC activity in adolescents during uncertain decision-making, providing preliminary support for a developmental model of GAD.