Text mining neuroscience journal articles to populate neuroscience databases.

We have developed a program NeuroText to populate the neuroscience databases in SenseLab (http://senselab.med.yale.edu/senselab) by mining the natural language text of neuroscience articles. NeuroText uses a two-step approach to identify relevant articles. The first step (pre-processing), aimed at 100% sensitivity, identifies abstracts containing database keywords. In the second step, potentially relevant abstracts identified in the first step are processed for specificity dictated by database architecture, and neuroscience, lexical and semantic contexts. NeuroText results were presented to the experts for validation using a dynamically generated interface that also allows expert-validated articles to be automatically deposited into the databases. Of the test set of 912 articles, 735 were rejected at the pre-processing step. For the remaining articles, the accuracy of predicting database-relevant articles was 85%. Twenty-two articles were erroneously identified. NeuroText deferred decisions on 29 articles to the expert. A comparison of NeuroText results versus the experts' analyses revealed that the program failed to correctly identify articles' relevance due to concepts that did not yet exist in the knowledgebase or due to vaguely presented information in the abstracts. NeuroText uses two "evolution" techniques (supervised and unsupervised) that play an important role in the continual improvement of the retrieval results. Software that uses the NeuroText approach can facilitate the creation of curated, special-interest, bibliography databases.

Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment.

The retina consists of ordered arrays of individual types of neurons for processing vision. Here, we show that such order is necessary for intrinsically photosensitive retinal ganglion cells (ipRGCs) to function as irradiance detectors. We found that during development, ipRGCs undergo proximity-dependent Bax-mediated apoptosis. Bax mutant mice exhibit disrupted ipRGC spacing and dendritic stratification with an increase in abnormally localized synapses. ipRGCs are the sole conduit for light input to circadian photoentrainment, and either their melanopsin-based photosensitivity or ability to relay rod/cone input is sufficient for circadian photoentrainment. Remarkably, the disrupted ipRGC spacing does not affect melanopsin-based circadian photoentrainment but severely impairs rod/cone-driven photoentrainment. We demonstrate reduced rod/cone-driven cFos activation and electrophysiological responses in ipRGCs, suggesting that impaired synaptic input to ipRGCs underlies the photoentrainment deficits. Thus, for irradiance detection, developmental apoptosis is necessary for the spacing and connectivity of ipRGCs that underlie their functioning within a neural network.

Relation between potassium-channel kinetics and the intrinsic dynamics in isolated retinal bipolar cells.

Characterization of the intrinsic dynamics of isolated retinal bipolar cells by a whole-cell patch-clamp technique combined with estimation of effective impulse responses across a range of mean injected currents reveals strikingly adaptive behavior. At resting potential, bipolar cells' effective impulse response is slow, high gain, and low pass. Depolarization speeds up response, decreases gain, and, in most cells, induces bandpass behavior. This adaptive behavior involves two K(+) currents. The delayed-rectifier accounts for the observed gain reduction, speed increase, and bandpass behavior. The A-channel further shortens the impulse responses but suppresses bandpass features. Computer simulations of model neurons with a delayed-rectifier and varying A-channel conductances reveal that impulse responses largely reflect the flux of electrical charge through the two K(+) channels. The A-channel broadens the frequency response and preempts the action of the delayed-rectifier, thereby reducing the associated bandpass features. Admixtures of the two K(+) channels produce the observed variety of dynamics of retinal bipolar cells.

Role of hyperpolarization-activated currents for the intrinsic dynamics of isolated retinal neurons.

The intrinsic dynamics of bipolar cells and rod photoreceptors isolated from tiger salamanders were studied by a patch-clamp technique combined with estimation of effective impulse responses across a range of mean membrane voltages. An increase in external K(+) reduces the gain and speeds the response in bipolar cells near and below resting potential. High external K(+) enhances the inward rectification of membrane potential, an effect mediated by a fast, hyperpolarization-activated, inwardly rectifying potassium current (K(IR)). External Cs(+) suppresses the inward-rectifying effect of external K(+). The reversal potential of the current, estimated by a novel method from a family of impulse responses below resting potential, indicates a channel that is permeable predominantly to K(+). Its permeability to Na(+), estimated from Goldman-Hodgkin-Katz voltage equation, was negligible. Whereas the activation of the delayed-rectifier K(+) current causes bandpass behavior (i.e., undershoots in the impulse responses) in bipolar cells, activation of the K(IR) current does not. In contrast, a slow hyperpolarization-activated current (I(h)) in rod photoreceptors leads to pronounced, slow undershoots near resting potential. Differences in the kinetics and ion selectivity of hyperpolarization-activated currents in bipolar cells (K(IR)) and in rod photoreceptors (I(h)) confer different dynamical behavior onto the two types of neurons.