Removal of area CA3 from hippocampal slices induces postsynaptic plasticity at Schaffer collateral synapses that normalizes CA1 pyramidal cell discharge.

Neural networks that undergo acute insults display remarkable reorganization. This injury related plasticity is thought to permit recovery of function in the face of damage that cannot be reversed. Previously, an increase in the transmission strength at Schaffer collateral to CA1 pyramidal cell synapses was observed after long-term activity reduction in organotypic hippocampal slices. Here we report that, following acute preparation of adult rat hippocampal slices and surgical removal of area CA3, input to area CA1 was reduced and Schaffer collateral synapses underwent functional strengthening. This increase in synaptic strength was limited to Schaffer collateral inputs (no alteration to temporoammonic synapses) and acted to normalize postsynaptic discharge, supporting a homeostatic or compensatory response. Short-term plasticity was not altered, but an increase in immunohistochemical labeling of GluA1 subunits was observed in the stratum radiatum (but not stratum moleculare), suggesting increased numbers of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and a postsynaptic locus of expression. Combined, these data support the idea that, in response to the reduction in presynaptic activity caused by removal of area CA3, Schaffer collateral synapses undergo a relatively rapid increase in functional efficacy likely supported by insertion of more AMPARs, which maintains postsynaptic excitability in CA1 pyramidal neurons. This novel fast compensatory plasticity exhibits properties that would allow it to maintain optimal network activity levels in the hippocampus, a brain structure lauded for its ongoing experience-dependent malleability.

Environmental influences on neural systems of relational complexity.

Constructivist learning theory contends that we construct knowledge by experience and that environmental context influences learning. To explore this principle, we examined the cognitive process relational complexity (RC), defined as the number of visual dimensions considered during problem solving on a matrix reasoning task and a well-documented measure of mature reasoning capacity. We sought to determine how the visual environment influences RC by examining the influence of color and visual contrast on RC in a neuroimaging task. To specify the contributions of sensory demand and relational integration to reasoning, our participants performed a non-verbal matrix task comprised of color, no-color line, or black-white visual contrast conditions parametrically varied by complexity (relations 0, 1, 2). The use of matrix reasoning is ecologically valid for its psychometric relevance and for its potential to link the processing of psychophysically specific visual properties with various levels of RC during reasoning. The role of these elements is important because matrix tests assess intellectual aptitude based on these seemingly context-less exercises. This experiment is a first step toward examining the psychophysical underpinnings of performance on these types of problems. The importance of this is increased in light of recent evidence that intelligence can be linked to visual discrimination. We submit three main findings. First, color and black-white visual contrast (BWVC) add demand at a basic sensory level, but contributions from color and from BWVC are dissociable in cortex such that color engages a "reasoning heuristic" and BWVC engages a "sensory heuristic." Second, color supports contextual sense-making by boosting salience resulting in faster problem solving. Lastly, when visual complexity reaches 2-relations, color and visual contrast relinquish salience to other dimensions of problem solving.

Digital reconstructions of neuronal morphology: three decades of research trends.

The importance of neuronal morphology has been recognized from the early days of neuroscience. Elucidating the functional roles of axonal and dendritic arbors in synaptic integration, signal transmission, network connectivity, and circuit dynamics requires quantitative analyses of digital three-dimensional reconstructions. We extensively searched the scientific literature for all original reports describing reconstructions of neuronal morphology since the advent of this technique three decades ago. From almost 50,000 titles, 30,000 abstracts, and more than 10,000 full-text articles, we identified 902 publications describing ∼44,000 digital reconstructions. Reviewing the growth of this field exposed general research trends on specific animal species, brain regions, neuron types, and experimental approaches. The entire bibliography, annotated with relevant metadata and (wherever available) direct links to the underlying digital data, is accessible at NeuroMorpho.Org.

NeuroMorpho.Org implementation of digital neuroscience: dense coverage and integration with the NIF.

Neuronal morphology affects network connectivity, plasticity, and information processing. Uncovering the design principles and functional consequences of dendritic and axonal shape necessitates quantitative analysis and computational modeling of detailed experimental data. Digital reconstructions provide the required neuromorphological descriptions in a parsimonious, comprehensive, and reliable numerical format. NeuroMorpho.Org is the largest web-accessible repository service for digitally reconstructed neurons and one of the integrated resources in the Neuroscience Information Framework (NIF). Here we describe the NeuroMorpho.Org approach as an exemplary experience in designing, creating, populating, and curating a neuroscience digital resource. The simple three-tier architecture of NeuroMorpho.Org (web client, web server, and relational database) encompasses all necessary elements to support a large-scale, integrate-able repository. The data content, while heterogeneous in scientific scope and experimental origin, is unified in format and presentation by an in house standardization protocol. The server application (MRALD) is secure, customizable, and developer-friendly. Centralized processing and expert annotation yields a comprehensive set of metadata that enriches and complements the raw data. The thoroughly tested interface design allows for optimal and effective data search and retrieval. Availability of data in both original and standardized formats ensures compatibility with existing resources and fosters further tool development. Other key functions enable extensive exploration and discovery, including 3D and interactive visualization of branching, frequently measured morphometrics, and reciprocal links to the original PubMed publications. The integration of NeuroMorpho.Org with version-1 of the NIF (NIFv1) provides the opportunity to access morphological data in the context of other relevant resources and diverse subdomains of neuroscience, opening exciting new possibilities in data mining and knowledge discovery. The outcome of such coordination is the rapid and powerful advancement of neuroscience research at both the conceptual and technological level.

The neuroscience information framework: a data and knowledge environment for neuroscience.

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience's Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov , http://neurogateway.org , and other sites as they come on line.