Faculty Bibliography

Information transfer analysis [G. A. Miller and P. E. Nicely, J. Acoust. Soc. Am. 27, 338-352 (1955)] is a tool used to measure the extent to which speech features are transmitted to a listener, e.g., duration or formant frequencies for vowels; voicing, place and manner of articulation for consonants. An information transfer of 100% occurs when no confusions arise between phonemes belonging to different feature categories, e.g., between voiced and voiceless consonants. Conversely, an information transfer of 0% occurs when performance is purely random. As asserted by Miller and Nicely, the maximum-likelihood estimate for information transfer is biased to overestimate its true value when the number of stimulus presentations is small. This small-sample bias is examined here for three cases: a model of random performance with pseudorandom data, a data set drawn from Miller and Nicely, and reported data from three studies of speech perception by hearing impaired listeners. The amount of overestimation can be substantial, depending on the number of samples, the size of the confusion matrix analyzed, as well as the manner in which data are partitioned therein

MYH9 encodes a class II nonmuscle myosin heavy chain-A (NMHC-IIA), a widely expressed 1960 amino acid polypeptide, with translated molecular weight of 220 kDa. From studies of type II myosin in invertebrates and analogy with the skeletal and smooth muscle myosin II, NMHC-IIA is considered to be involved in diverse cellular functions, including cell shape, motility and division. The current study assessed the consequences of two separate, naturally occurring MYH9 dominant mutant alleles, MYH9(R702C) and MYH9(R705H) linked to syndromic and nonsyndromic hearing loss, respectively, upon diverse NMHC-IIA related functions in two separate cultured cell lines. MYH9-siRNA-induced inhibition of NMHC-IIA in HeLa cells or HEK293 cells resulted in alterations in their shape, actin cytoskeleton and adhesion properties. However, HeLa or HEK293 cells transfected with naturally occurring MYH9 mutant alleles, MYH9(R702C) or MYH9(R705H), as well as in vitro generated deletion derivatives, MYH9(DeltaN592) or MYH9(DeltaC570), were unaffected. The effects of MYH9-siRNA-induced suppression underline the critical role of NMHC-IIA in maintenance of cell shape and adhesion. However, the results also indicate that the NMHC-IIA mutants, R702C and R705H do not inactivate or suppress the endogenous wild type NMHC-IIA within the HeLa or HEK293 cell assay system. Cell Motil. Cytoskeleton 2008. (c) 2008 Wiley-Liss, Inc

How do I choose a mentor? How do I decide what field of neuroscience to work in? Should I consider doing research in industry? Most students and postdoctoral researchers aiming for a successful career in neuroscience ask themselves these questions. In this article, Nature Reviews Neuroscience asks four successful neuroscientists for their thoughts on the factors one should consider when making these decisions. We hope that this Viewpoint will serve as a useful resource for junior neuroscientists who have to make important and sometimes difficult decisions that might have long-lasting consequences for their careers

Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) in the hippocampus requires rapid protein synthesis, which suggests that mGluR activation is coupled to signaling pathways that regulate translation. Herein, we have investigated the signaling pathways that couple group I mGluRs to ribosomal S6 protein phosphorylation and 5'oligopyrimidine tract (5'TOP)-encoded protein synthesis during mGluR-LTD. We found that mGluR-LTD was associated with increased phosphorylation of p70S6 kinase (S6K1) and S6, as well as the synthesis of the 5'TOP-encoded protein elongation factor 1A (EF1A). Moreover, we found that LTD-associated increases in S6K1 phosphorylation, S6 phosphorylation, and levels of EF1A were sensitive to inhibitors of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular signal-regulated kinase (ERK). However, mGluR-LTD was normal in S6K1 knockout mice and enhanced in both S6K2 knockout mice and S6K1/S6K2 double knockout mice. In addition, we observed that LTD-associated increases in S6 phosphorylation were still increased in S6K1- and S6K2-deficient mice, whereas basal levels of EF1A were abnormally elevated. Taken together, these findings indicate that mGluR-LTD is associated with PI3K-, mTOR-, and ERK-dependent alterations in the phosphorylation of S6 and S6K. Our data also suggest that S6Ks are not required for the expression of mGluR-LTD and that the synthesis of 5'TOP-encoded proteins is independent of S6Ks during mGluR-LTD

Over hundreds of millions of years, evolution has optimized brain design to maximize its functionality while minimizing costs associated with building and maintenance. This observation suggests that one can use optimization theory to rationalize various features of brain design. Here, we attempt to explain the dimensions and branching structure of dendritic arbors by minimizing dendritic cost for given potential synaptic connectivity. Assuming only that dendritic cost increases with total dendritic length and path length from synapses to soma, we find that branching, planar, and compact dendritic arbors, such as those belonging to Purkinje cells in the cerebellum, are optimal. The theory predicts that adjacent Purkinje dendritic arbors should spatially segregate. In addition, we propose two explicit cost function expressions, falsifiable by measuring dendritic caliber near bifurcations.

Objective Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders. Method The authors conducted a prospective longitudinal study of 176 methylphenidate-treated Caucasian male children (ages 6 to 12) with ADHD but without conduct disorder. The participants were followed up at late adolescence (mean age=18.4 years; retention rate=94%) and adulthood (mean age=25.3; retention rate=85%). One hundred seventy-eight comparison subjects also were included. All subjects were diagnosed by blinded clinicians. The Cox proportional hazards model included the following childhood predictor variables: age at initiation of methylphenidate treatment, total cumulative dose of methylphenidate, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopathology. Separate models tested for the following four lifetime outcomes: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, and stimulant use disorder. Other outcomes included antisocial personality, mood, and anxiety disorders. Results There was a significant positive relationship between age at treatment initiation and non-alcohol substance use disorder. None of the predictor variables accounted for this association. Post hoc analyses showed that the development of antisocial personality disorder explained the relationship between age at first methylphenidate treatment and later substance use disorder. Even when controlling for substance use disorder, age at stimulant treatment initiation was significantly and positively related to the later development of antisocial personality disorder. Age at first methylphenidate treatment was unrelated to mood and anxiety disorders. Conclusions Early age at initiation of methylphenidate treatment in children with ADHD does not increase the risk for negative outcomes and may have beneficial long-term effects

Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001-2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain

We study cardiac action potential propagation under severe reduction in gap junction conductance. We use a mathematical model of cellular electrical activity that takes into account both three-dimensional geometry and ionic concentration effects. Certain anatomical and biophysical parameters are varied to see their impact on cardiac action potential conduction velocity. This study uncovers quantitative features of ephaptic propagation that differ from previous studies based on one-dimensional models. We also identify a mode of cardiac action potential propagation in which the ephaptic and gap-junction-mediated mechanisms alternate. Our study demonstrates the usefulness of this modeling approach for electrophysiological systems especially when detailed membrane geometry plays an important role