Faculty Bibliography

The formation of neuromuscular synapses requires a complex exchange of signals between motor neurons and skeletal muscle fibers. Essential for the formation of neuromuscular junction (NMJ) is the activation of MuSK, a muscle-specific receptor tyrosine kinase (DeChiara et al., 1996). In mice lacking MuSK, motor axons fail to stop and differentiate, acetylcholine receptors (AChRs) fail to cluster, and AChR genes are expressed uniformly in muscle (DeChiara et al., 1996; Gautam et al., 1996). The retrograde signals for presynaptic differentiation are not known. Because synapse-specific transcription, like presynaptic differentiation, is MuSK-dependent, it is possible that retrograde signals for presynaptic differentiation might be encoded by genes that are expressed preferentially by synaptic nuclei. To identify such synapse-specific genes we screened Affymetrix microarrays with RNA from the dissected, synapse-enriched, and extrasynaptic regions of skeletal muscle and further studied those genes that encode for the secreted or cell-surface proteins

Pacemaker cells in the heart generate periodic electrical signals that are conducted to the working myocardium via the specialized conduction system. Effective cell-to-cell communication is critical for rapid, uniform conduction of cardiac action potentials-- a prerequisite for effective, synchronized cardiac contraction. Local circuit currents form the basis of the depolarization wave front in the working myocardium. These currents flow from cell to cell via gap junction channels. In this chapter, we trace the path of the action potential from its generation in the sinus node to propagation through the working myocardium, with a detailed discussion of the role of gap junctions. First, we review the transmembrane ionic currents and the basic principles of conduction of the action potential to the working myocardium via the specialized tissues of the heart. Next, we consider the relative contribution of cell geometry, size, and gap junction conductance. These factors are examined in terms of their source-to-sink relationships. Lastly, we will discuss new insights into the importance of gap junctions in cardiac conduction in health and disease which have been gained from high resolution optical mapping in connexin-deficient mice

In non-avian reptiles the medial and dorsal cortices are putative homologues of the hippocampal formation in mammals and birds. Studies on mammals and birds commonly report neuro-ecological correlations between hippocampal volume and aspects of spatial ecology. We examined the relationship between putative homologous cortical volumes and spatial use in a population of the squamate reptile, Agkistrodon piscivorus, that exhibits sex differences in spatial use. Do male A. piscivorus that inhabit larger home ranges than females also have larger putative hippocampal volumes? Male and female brains were sectioned and digitized to quantify regional cortical volumes. Although sex differences in dorsal cortex volume were not observed, males had a significantly larger medial cortex relative to telencephalon volume. Similar to studies on mammals and birds, relative hippocampal or medial cortex volume was positively correlated with patterns of spatial use. We demonstrate volumetric sex differences within a reptilian putative hippocampal homologue

In this paper, we present a novel method for automatically extracting the tagging sheets in tagged cardiac MR images, and tracking their displacement during the heart cycle, using a tunable 3D Gabor filter bank. Tagged MRI is a non-invasive technique for the study of myocardial deformation. We design the 3D Gabor filter bank based on the geometric characteristics of the tagging sheets. The tunable parameters of the Gabor filter bank are used to adapt to the myocardium deformation. The whole 3D image dataset is convolved with each Gabor filter in the filter bank, in the Fourier domain. Then we impose a set of deformable meshes onto the extracted tagging sheets and track them over time. Dynamic estimation of the filter parameters and the mesh internal smoothness are used to help the tracking. Some very encouraging results are shown

In this paper we present a robust method for segmenting and tracking cardiac contours and tags in 4D cardiac MRI tagged images via spatio-temporal propagation. Our method is based on two main techniques: the Metamorphs segmentation for robust boundary estimation, and the tunable Gabor filter bank for tagging lines enhancement, removal and myocardium tracking. We have developed a prototype system based on the integration of these two techniques, and achieved efficient, robust segmentation and tracking with minimal human interaction

The development of gene array techniques to quantify expression levels of dozens to thousands of genes simultaneously within selected tissue samples from control and diseased brain has enabled researchers to generate expression profiles of vulnerable neuronal populations in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, and Creutzfeld-Jakob disease. Intriguingly, gene expression analysis reveals that vulnerable brain regions in many of these diseases share putative pathogenetic alterations in common classes of genes, including decrements in synaptic transcript levels and increments in immune response transcripts. Thus, gene expression profiles of diseased neuronal populations may reveal mechanistic clues to the molecular pathogenesis underlying various neurological diseases and aid in identifying potential therapeutic targets. This chapter will review how regional and single cell gene array technologies have advanced our understanding of the genetics of human neurological disease.