Cellular Origin of Spontaneous Ganglion Cell Spike Activity in Animal Models of Retinitis Pigmentosa

Here we review evidence that loss of photoreceptors due to degenerative retinal disease causes an increase in the rate of spontaneous ganglion spike discharge. Information about persistent spike activity is important since it is expected to add noise to the communication between the eye and the brain and thus impact the design and effective use of retinal prosthetics for restoring visual function in patients blinded by disease. Patch-clamp recordings from identified types of ON and OFF retinal ganglion cells in the adult (36–210 d old) rd1 mouse show that the ongoing oscillatory spike activity in both cell types is driven by strong rhythmic synaptic input from presynaptic neurons that is blocked by CNQX. The recurrent synaptic activity may arise in a negative feedback loop between a bipolar cell and an amacrine cell that exhibits resonant behavior and oscillations in membrane potential when the normal balance between excitation and inhibition is disrupted by the absence of photoreceptor input

Lightweight XML-based query, integration and visualization of distributed, multimodality brain imaging data

A need of many neuroimaging researchers is to integrate multimodality brain data that may be stored in separate databases. To address this need we have developed a framework that provides a uniform XML-based query interface across multiple online data sources. The development of this framework is driven by the need to integrate neurosurgical and neuroimaging data related to language. The data sources for the language studies are 1) a web-accessible relational database of neurosurgical cortical stimulation mapping data (CSM) that includes patient-specific 3-D coordinates of each stimulation site mapped to an MRI reconstruction of the patient brain surface; and 2) an XML database of fMRI and structural MRI data and analysis results, created automatically by a batch program we have embedded in SPM. To make these sources available for querying each is wrapped as an XML view embedded in a web service. A top level web application accepts distributed XQueries over the sources, which are dispatched to the underlying web services. Returned results can be displayed as XML, HTML, CSV (Excel format), a 2-D schematic of a parcellated brain, or a 3-D brain visualization. In the latter case the CSM patient-specific coordinates returned by the query are sent to a transformation web-service for conversion to normalized space, after which they are sent to our 3-D visualization program MindSeer, which is accessed via Java WebStart through a generated link. The anatomical distribution of pooled CSM sites can then be visualized using various surfaces derived from brain atlases. As this framework is further developed and generalized we believe it will have appeal for researchers who wish to query, integrate and visualize results across their own databases as well as those of collaborators

A Dendrite-Autonomous Mechanism for Direction Selectivity in Retinal Starburst Amacrine Cells

Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs) playing a major role. SACs generate larger dendritic Ca2+ signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS) in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca2+] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage–activated Ca2+ channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination

Understanding the interplay of increased pressure, residual heat and geologic and geochemical environment on radionuclide migration from underground nuclear tests

Understanding the processes that govern migration of radionuclides from underground nuclear tests is a problem of interest in many places in the world. Whether to gain understanding in the risks to human health, to guide water resources management decisions or as a surrogate for nuclear repository safety, there are a number of complex, coupled processes governing fate and form of radionuclides in the subsurface that need to be understood. These processes include the increased pore water pressure that is present after some underground nuclear tests, the residual heat signature from the nuclear detonation and the natural (i.e. pre-test) and altered (i.e. post-test) hydrogeologic and geochemical setting. We will focus on tests in saturated and unsaturated environments in Yucca Flat at the US Nevada Test Site. These tests all encompass a range of the aforementioned process interactions and provide insight into the broader context of understanding radionuclide migration from underground nuclear tests over a range of scale and environment

Neuroanatomical Domain of the Foundational Model of Anatomy Ontology

Background: The diverse set of human brain structure and function analysis methods represents a difficult challenge for reconciling multiple views of neuroanatomical organization. While different views of organization are expected and valid, no widely adopted approach exists to harmonize different brain labeling protocols and terminologies. Our approach uses the natural organizing framework provided by anatomical structure to correlate terminologies commonly used in neuroimaging. Description: The Foundational Model of Anatomy (FMA) Ontology provides a semantic framework for representing the anatomical entities and relationships that constitute the phenotypic organization of the human body. In this paper we describe recent enhancements to the neuroanatomical content of the FMA that models cytoarchitectural and morphological regions of the cerebral cortex, as well as white matter structure and connectivity. This modeling effort is driven by the need to correlate and reconcile the terms used in neuroanatomical labeling protocols. By providing an ontological framework that harmonizes multiple views of neuroanatomical organization, the FMA provides developers with reusable and computable knowledge for a range of biomedical applications. Conclusions: A requirement for facilitating the integration of basic and clinical neuroscience data from diverse sources is a well-structured ontology that can incorporate, organize, and associate neuroanatomical data. We applied the ontological framework of the FMA to align the vocabularies used by several human brain atlases, and to encode emerging knowledge about structural connectivity in the brain. We highlighted several use cases of these extensions, including ontology reuse, neuroimaging data annotation, and organizing 3D brain models

Distributed XQuery-based integration and visualization of multimodality data: Application to brain mapping.

This paper addresses the need for relatively small groups of collaborating investigators to integrate distributed and heterogeneous data about the brain. Although various national efforts facilitate large-scale data sharing, these approaches are generally too “heavyweight” for individual or small groups of investigators, with the result that most data sharing among collaborators continues to be ad hoc. Our approach to this problem is to create a “lightweight” distributed query architecture, in which data sources are accessible via web services that accept arbitrary query languages but return XML results. A Distributed XQuery Processor (DXQP) accepts distributed XQueries in which subqueries are shipped to the remote data sources to be executed, with the resulting XML integrated by DXQP. A web-based application called DXBrain accesses DXQP, allowing a user to create, save and execute distributed XQueries, and to view the results in various formats including a 3-D brain visualization. Example results are presented using distributed brain mapping data sources obtained in studies of language organization in the brain, but any other XML source could be included. The advantage of this approach is that it is very easy to add and query a new source, the tradeoff being that the user needs to understand XQuery and the schemata of the underlying sources. For small numbers of known sources this burden is not onerous for a knowledgeable user, leading to the conclusion that the system helps to fill the gap between ad hoc local methods and large scale but complex national data sharing efforts