Faculty Bibliography

Large and long-lasting cytosolic calcium surges in astrocytes have been described in cultured cells and acute slice preparations. The mechanisms that give rise to these calcium events have been extensively studied in vitro. However, their existence and functions in the intact brain are unknown. We have topically applied Fluo-4 AM on the cerebral cortex of anesthetized rats, and imaged cytosolic calcium fluctuation in astrocyte populations of superficial cortical layers in vivo, using two-photon laser scanning microscopy. Spontaneous [Ca(2+)](i) events in individual astrocytes were similar to those observed in vitro. Coordination of [Ca(2+)](i) events among astrocytes was indicated by the broad cross-correlograms. Increased neuronal discharge was associated with increased astrocytic [Ca(2+)](i) activity in individual cells and a robust coordination of [Ca(2+)](i) signals in neighboring astrocytes. These findings indicate potential neuron-glia communication in the intact brain

The performance of the brain is constrained by wiring length and maintenance costs. The apparently inverse relationship between number of neurons in the various interneuron classes and the spatial extent of their axon trees suggests a mathematically definable organization, reminiscent of 'small-world' or scale-free networks observed in other complex systems. The wiring-economy-based classification of cortical inhibitory interneurons is supported by the distinct physiological patterns of class members in the intact brain. The complex wiring of diverse interneuron classes could represent an economic solution for supporting global synchrony and oscillations at multiple timescales with minimum axon length

Transgenic mice have been created in an attempt to generate models of human Alzheimer's disease, but success has been partial and unpredictable. The overall aim of this paper is to illustrate how genomics can be used in translational research, turning genetic information in the form of pathogenic mutations into clinically useful drugs against a major human disease. This paper will illustrate how genetic information allows researchers to dissect the aetiology of a disease and then replicate the disease in vivo through the process of transgenesis. The limitations of recreating a condition like Alzheimer's disease in a transgenic mouse, how far the mice have advanced understanding of the disease and how useful they have been for the development of therapeutics will then be discussed

The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD

We describe the design of finite-size linear-phase separable kernels for differentiation of discrete multidimensional signals. The problem is formulated as an optimization of the rotation-invariance of the gradient operator, which results in a simultaneous constraint on a set of one-dimensional low-pass prefilter and differentiator filters up to the desired order. We also develop extensions of this formulation to both higher dimensions and higher order directional derivatives. We develop a numerical procedure for optimizing the constraint, and demonstrate its use in constructing a set of example filters. The resulting filters are significantly more accurate than those commonly used in the image and multidimensional signal processing literature

Objective methods for assessing perceptual image quality traditionally attempted to quantify the visibility of errors (differences) between a distorted image and a reference image using a variety of known properties of the human visual system. Under the assumption that human visual perception is highly adapted for extracting structural information from a scene, we introduce an alternative complementary framework for quality assessment based on the degradation of structural information. As a specific example of this concept, we develop a Structural Similarity Index and demonstrate its promise through a set of intuitive examples, as well as comparison to both subjective ratings and state-of-the-art objective methods on a database of images compressed with JPEG and JPEG2000

Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7.8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm(3). GM and WM comprised 50.4 +/- 3.8% and 30.4 +/- 5.0% (mean +/- standard deviation), respectively, of the total brain volume in the patients; 53.8 +/- 3.7% and 35.4 +/- 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% x 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined

A functional magnetic resonance imaging (fMRI) study was conducted during which seven subjects carried out naturalistic tactile object recognition (TOR) of real objects. Activation maps, conjunctions across subjects, were compared between tasks involving TOR of common real objects, palpation of 'nonsense' objects, and rest. The tactile tasks involved similar motor and sensory stimulation, allowing higher tactile recognition processes to be isolated. Compared to nonsense object palpation, the most prominent activation evoked by TOR was in secondary somatosensory areas in the parietal operculum (SII) and insula, confirming a modality-specific path for TOR. Prominent activation was also present in medial and lateral secondary motor cortices, but not in primary motor areas, supporting the high level of sensory and motor integration characteristic of object recognition in the tactile modality. Activation in a lateral occipitotemporal area associated previously with visual object recognition may support cross-modal collateral activation. Finally, activation in medial temporal and prefrontal areas may reflect a common final pathway of modality-independent object recognition. This study suggests that TOR involves a complex network including parietal and insular somatosensory association cortices, as well as occipitotemporal visual areas, prefrontal, and medial temporal supramodal areas, and medial and lateral secondary motor cortices. It confirms the involvement of somatosensory association areas in the recognition component of TOR, and the existence of a ventrolateral somatosensory pathway for TOR in intact subjects. It challenges the results of previous studies that emphasize the role of visual cortex rather than somatosensory association cortices in higher-level somatosensory cognition