Faculty Bibliography

Collagenous Alzheimer amyloid plaque component (CLAC) is a unique non-Abeta amyloid component of senile plaques (SP) derived from a transmembrane collagen termed CLAC-precursor. Here we characterize the chronological and spatial relationship of CLAC with other features of SP amyloid in the brains of patients with Alzheimer's disease (AD), Down syndrome (DS), and of PSAPP transgenic mice. In AD and DS cerebral cortex, CLAC invariably colocalized with Abeta42 but often lacked Abeta40- or thioflavin S (thioS)-reactivities. Immunoelectron microscopy of CLAC-positive SP showed labeling of fibrils that are more loosely dispersed compared to typical amyloid fibrils in CLAC-negative SP. In DS cerebral cortex, diffuse plaques in young patients were negative for CLAC, whereas a subset of SP became CLAC-positive in patients aged 35 to 50 years, before the appearance of Abeta40. In DS cases over 50 years of age, Abeta40-positive SP dramatically increased, whereas CLAC burden remained at a constant level. In PSAPP transgenic mice, CLAC was positive in the diffuse Abeta deposits surrounding huge-cored plaques. Thus, CLAC and Abeta40 or thioS exhibit mostly separate distribution patterns in SP, suggesting that CLAC is a relatively early component of SP in human brains that may have inhibitory effects against the maturation of SP into beta-sheet-rich amyloid deposits

We previously reported that sonic hedgehog (Shh) induces the differentiation of rat ventral forebrain neurons expressing a novel marker, EVF-1 [Development 125 (1998) 5079]. In this report, we show that EVF-1 is a novel, developmentally regulated, non-coding RNA, with no homology to other known non-coding RNA sequences. Sequence analysis, in vitro translation, and comparison of the rat and mouse EVF-1 sequences suggest that EVF-1 contains no protein coding regions. Chromosomal location indicates that EVF-1 maps adjacent to the Dlx6 gene on mouse chromosome 6. RNA in situ hybridization of the embryonic rat forebrain shows that EVF-1 is expressed by immature neurons in the subventricular zone and its expression decreases during forebrain development. Whole mount in situ hybridization shows that EVF-1 is expressed at high levels in the branchial arches, ventral forebrain, olfactory bulb, and limbs. EVF-1 expression is linked to Shh and the Dlx family of proteins, genes with a demonstrated importance to ventral forebrain and craniofacial development

PURPOSE: To determine whether diffusion-tensor magnetic resonance (MR) imaging metrics of peritumoral edema can be used to differentiate intra- from extraaxial lesions, metastatic lesions from gliomas, and high- from low-grade gliomas. MATERIALS AND METHODS: In this study, diffusion-tensor MR imaging was performed preoperatively in 40 patients with intracranial neoplasms, including meningiomas, metastatic lesions, glioblastomas multiforme, and low-grade gliomas. Histograms of mean diffusivity (MD) and fractional anisotropy (FA) were used to analyze both the tumor and the associated T2 signal intensity abnormality. An additional metric, the tumor infiltration index (TII), was evaluated. The TII is a measure of the change in FA presumably caused by tumor cells infiltrating the peritumoral edema. Student t test and least-squares linear regression analyses were performed. RESULTS: Peritumoral MD and FA values indicated no statistically significant difference between intra- and extraaxial lesions or between high- and low-grade gliomas. Regarding intraaxial tumors, the measured mean peritumoral MD of metastatic lesions, 0.733 x 10(-3) mm(2)/sec +/- 0.061 (SD), was significantly higher than that of gliomas, 0.587 +/- 0.093 x 10(-3) mm(2)/sec (P <.05). There was also a statistically significant difference between the TIIs of the edema surrounding meningiomas and metastases (mean, 0 +/- 35) and the TIIs of the edema surrounding gliomas (mean, 64 +/- 59) (P <.05). CONCLUSION: Peritumoral diffusion-tensor MR imaging metrics enable the differentiation of solitary intraaxial metastatic brain tumors from gliomas. In addition, the TII enables one to distinguish presumed tumor-infiltrated edema from purely vasogenic edema

PURPOSE: To investigate the feasibility of diffusion tensor imaging (DTI) assessment of microscopic fiber tract injury in the corpus callosum (CC) and other normal-appearing white matter (NAWM) in patients with early multiple sclerosis (MS). MATERIALS AND METHODS: DTI was performed in 12 healthy volunteers and 15 patients who have relatively short disease duration (mean = 2.7 years). Both fractional anisotropy (FA) and mean diffusivity (MD) were obtained in different regions of normal-appearing CC (NACC) and NAWM in frontal and occipital regions. RESULTS: The data showed significantly lower FA (P < 0.001) and higher MD (P < 0.04) for NACC regions, but not for frontal and occipital NAWM regions, in patients than in those in healthy volunteers after Bonferroni adjustment. The increase of MD in the entire NACC regions was correlated with the total cerebral lesion volume (r = 0.75, P = 0.001) in patients. CONCLUSION: The water diffusion changes indicate that in the early phase of disease there is a preferential occult injury of CC, which is likely due to the Wallerian degeneration from distant lesions

Prolonged exposure to a stimulus, called 'adaptation', reduces cortical responsiveness. Adaptation has been studied extensively in primary visual cortex (V1), where responsivity is usually reduced most when the adapting and test stimuli are well matched. Theories about the functional benefits of adaptation have relied on this specificity, but the resultant changes in neuronal tuning are of the wrong type to account for well-documented perceptual aftereffects. Here we have used moving sinusoidal gratings to study the effect of adaptation on the direction tuning of neurons in area MT in macaques. Responsivity in MT is maintained best in the adapted direction and is strongly reduced for nearby directions. Consequently, adaptation in the preferred direction reduces the direction-tuning bandwidth, whereas adaptation at near-preferred directions causes tuning to shift toward the adapted direction. This previously unknown effect of adaptation is consistent with perceptual aftereffects and indicates that different cortical regions may adjust to constant sensory input in distinct ways

The olivo-cerebellar system is one of the central networks organizing movement coordination in vertebrates. This system consists of three main anatomical structures: the inferior olive (10), the cerebellar nuclei, and the cerebellar cortex. Over the last four decades studies in many laboratories have contributed significantly to our understanding of the electrophysiology of 10 and cerebellar neurons. However, addressing the dynamic properties of olivo-cerebellar network requires information beyond the limits attainable using single cell recordings. Research at the neuronal network level is presently being implemented in order to determine the spatiotemporal activity profiles of ensemble neuronal activity using optical imaging of voltage-sensitive dye signals. We summarize here results of such type of study using the in vitro 10 slices. The dynamic characteristic of the system is addressed using the imaging results as well as mathematical modeling of the network, as a heuristic tool. A computer-based control system based on such biological findings is outlined

OBJECTIVE: To review contemporary molecular biological literature related to skull base tumor biology and tumorigenesis. DATA SOURCES: PUBMED and Ovid literature searches were performed using keyword search. Only English language articles published between 1965 and December 4, 2003 were chosen. STUDY SELECTION AND DATA EXTRACTION: All relevant articles from the past 8 years, as well as landmark articles in years before 1995, were retrieved and reviewed. CONCLUSION: Consistent progress is being made toward the molecular genetic and biological basis of the most common skull base tumors. An understanding of these mechanisms will aid the neurotologist in future diagnosis and management of the lesions

Recent advances in microelectrode array technology now permit a direct examination of the way populations of sensory neurons encode information about a limb's position in space. To address this issue, we recorded nerve impulses from about 100 single units simultaneously in the L6 and L7 dorsal root ganglia (DRG) of the anesthetized cat. Movement sensors, placed near the hip, knee, ankle, and foot, recorded passive movements of the cat's limb while it was moved pseudo-randomly. The firing rate of the neurons was correlated with the position of the limb in various coordinate systems. The firing rates were less correlated to the position of the foot in Cartesian coordinates (x, y) than in joint angular coordinates (hip, knee, ankle), or in polar coordinates. A model was developed in which position and its derivatives are encoded linearly, followed by a nonlinear spike-generating process. Adding the nonlinear portion significantly increased the correlations in all coordinate systems, and the full models were able to accurately predict the firing rates of various types of sensory neurons. The observed residual variability is captured by a simple stochastic model. Our results suggest that compact encoding models for primary afferents recorded at the DRG are well represented in polar coordinates, as has previously been suggested for the cortical and spinal representation of movement. This study illustrates how sensory receptors encode a sense of limb position, and it provides a general framework for modeling sensory encoding by populations of neurons.