Faculty Bibliography

Semicircular canals have been sensors of angular acceleration for 450 million years. This vertebrate adaptation enhances survival by implementing postural and visual stabilization during motion in a three-dimensional environment. We used an integrated neuroethological approach in larval Xenopus to demonstrate that semicircular canal dimensions, and not the function of other elements, determines the onset of angular acceleration detection. Before angular vestibuloocular function in either the vertical or horizontal planes, at stages 47 and 48, respectively, each individual component of the vestibuloocular system was shown to be operational: extraocular muscles could be activated, central neural pathways were complete, and canal hair cells were capable of evoking graded responses. For Xenopus, a minimum semicircular canal lumen radius of 60 microm was necessary to permit endolymph displacement sufficient for sensor function at peak accelerations of 400 degrees /s(2). An intra-animal comparison demonstrated that this size is reached in the vertical canals earlier in development than in the horizontal canals, corresponding to the earlier onset of vertical canal-activated ocular motor behavior. Because size constitutes a biophysical threshold for canal-evoked behavior in other vertebrates, such as zebrafish, we suggest that the semicircular canal lumen and canal circuit radius are limiting the onset of vestibular function in all small vertebrates. Given that the onset of gravitoinertial acceleration detection precedes angular acceleration detection by up to 10 d in Xenopus, these results question how the known precise spatial patterning of utricular and canal afferents in adults is achieved during development

Animals process information about many stimulus features simultaneously, swiftly (in a few 100 ms), and robustly (even when individual neurons do not themselves respond reliably). When the brain carries, codes, and certainly when it decodes information, it must do so through some coarse-grained projection mechanism. How can a projection retain information about network dynamics that covers multiple features, swiftly and robustly? Here, by a coarse-grained projection to event trees and to the event chains that comprise these trees, we propose a method of characterizing dynamic information of neuronal networks by using a statistical collection of spatial-temporal sequences of relevant physiological observables (such as sequences of spiking multiple neurons). We demonstrate, through idealized point neuron simulations in small networks, that this event tree analysis can reveal, with high reliability, information about multiple stimulus features within short realistic observation times. Then, with a large-scale realistic computational model of V1, we show that coarse-grained event trees contain sufficient information, again over short observation times, for fine discrimination of orientation, with results consistent with recent experimental observation

RATIONALE: Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy. OBJECTIVES: To test the predictive value of interleukin (IL)-8 for 28-day mortality in pediatric septic shock. METHODS: A training data set (n = 40) identified a serum IL-8 of greater than 220 pg/ml as having a 75% sensitivity and specificity for predicting 28-day mortality. This cutoff was then subjected to a series of validation steps. MEASUREMENTS AND MAIN RESULTS: Subjects were drawn from two large, independent pediatric septic shock databases. Prospective application of the IL-8 cutoff to validation data set 1 (n = 139) demonstrated 78% sensitivity and 64% specificity for 28-day mortality. A serum IL-8 level of 220 pg/ml or less, however, had a negative predictive value for 28-day mortality of 95% in validation data set 1, which was subsequently applied to an independently generated data set of children with septic shock (validation set 2, n = 193). A serum IL-8 level of 220 pg/ml or less had a negative predictive value for 28-day mortality of 94% when applied to validation set 2. CONCLUSIONS: A serum IL-8 level of 220 pg/ml or less, obtained within 24 hours of admission, predicts a high likelihood of survival in children with septic shock. We propose that IL-8 can be used to exclude such patients from interventional clinical trials and ultimately derive a study population with a more favorable risk to benefit ratio when subjected to a study agent

Responses of on-center starburst amacrine cells to steady light stimuli were recorded in the dark-adapted mouse retina. The response to spots of dim white light appear to show two components, an initial peak that correspond to the onset of the light stimulus and a series of oscillations that ride on top of the initial peak relaxation. The frequency of oscillations during light stimulation was three time higher than the frequency of spontaneous oscillations recorded in the dark. The light-evoked responses in starburst cells were exclusively dependent on the release of glutamate likely from presynaptic bipolar axon terminals and the binding of glutamate to AMPA/kainate receptors because they were blocked by 6-cyano-7-nitroquinoxalene-2,3-dione. The synaptic pathway responsible for the light responses was blocked by AP4, an agonist of metabotropic glutamate receptors that hyperpolarize on-center bipolar cells on activation. Light responses were inhibited by the calcium channel blockers cadmium ions and nifedipine, suggesting that the release of glutamate was calcium dependent. The oscillatory component of the response was specifically inhibited by blocking the glutamate transporter with d-threo-beta-benzyloxyaspartic acid, suggesting that glutamate reuptake is necessary for the oscillatory release. GABAergic antagonists bicuculline, SR 95531, and picrotoxin increased the amplitude of the initial peak while they inhibit the frequency of oscillations. TTX had a similar effect. Strychnine, the blocker of glycine receptors did not affect the initial peak but strongly decreased the oscillations frequency. These inhibitory inputs onto the bipolar axon terminals shape and synchronize the oscillatory component

Abnormal protein deposits are a common feature of many human diseases including Alzheimer's disease. In Alzheimer's disease, the appearance of tangles, composed of the microtubule associated protein tau, correlates with both cell death and symptom severity. However, are tau filaments simply markers of disease progression, or are they directly responsible for cell death? Due to conflicting findings from cell and animal models, it remains controversial whether tau polymers or smaller pre-fibrillar aggregates or tau monomers are the toxic species. Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. This review will examine the findings regarding the toxicity of various tau species

BACKGROUND: We investigated the effects of exogenous GS on hypoxia- and GABA(A) receptor-induced axonal depression in neonatal rats. METHODS: To assess the effects of GS on spinal cord axons, CAPs were recorded. Hemicords were exposed to hypoxia by 30-minute superfusion with Ringer's solution saturated with 95% N(2) and 5% CO(2) followed by 60-minute exposure to 95% N(2) and 5% CO(2) gassing (N(2) gassing phase) and then 90 minutes of resuperfusion with oxygenated Ringer's solution (resuperfusion phase). Exogenous high GS (15 U) or low GS (1.5 U) was delivered during the N(2) gassing phase. The effects of GS on GABA(A) receptor-induced axonal depression were analyzed with oxygenated isolated dorsal columns. RESULTS: The high GS significantly reduced the decline in the CAP amplitudes during the N(2) gassing and resuperfusion phases (P = .0185) compared to the hypoxia control. The low GS treatment showed a trend toward recovery during the N(2) gassing and resuperfusion phases, but the effect was not significant (P = .3953). In isolated dorsal columns, GS significantly reduced the CAP amplitude depression induced by GABA(A) receptor agonist. CONCLUSIONS: Our findings suggest that GS had dose-dependent protective effects on the spinal cord against hypoxia-induced axonal depression. It may inhibit the depression of CAP amplitudes by blocking GABA(A) receptors

Image denoising methods are often designed to minimize mean-squared error (MSE) within the subbands of a multiscale decomposition. However, most high-quality denoising results have been obtained with overcomplete representations, for which minimization of MSE in the subband domain does not guarantee optimal MSE performance in the image domain. We prove that, despite this suboptimality, the expected image-domain MSE resulting from applying estimators to subbands that are made redundant through spatial replication of basis functions (e.g., cycle spinning) is always less than or equal to that resulting from applying the same estimators to the original nonredundant representation. In addition, we show that it is possible to further exploit overcompleteness by jointly optimizing the subband estimators for image-domain MSE. We develop an extended version of Stein's unbiased risk estimate (SURE) that allows us to perform this optimization adaptively, for each observed noisy image. We demonstrate this methodology using a new class of estimator formed from linear combinations of localized 'bump' functions that are applied either pointwise or on local neighborhoods of subband coefficients. We show through simulations that the performance of these estimators applied to overcomplete subbands and optimized for image-domain MSE is substantially better than that obtained when they are optimized within each subband. This performance is, in turn, substantially better than that obtained when they are optimized for use on a nonredundant representation