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Cell-Type Specific Transcriptomic Profiling To Dissect Mechanisms Of Differential Dendritogenesis, Surajit Bhattacharya, Eswar Prasad R. Iyer, Srividya Chandramouli Iyer, Daniel N. Cox

Neuroscience Institute Faculty Publications

The establishment, maintenance and modulation of cell-type specific neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the specification of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from purified populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression profiling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with …

Deep Learning For Neuroimaging: A Validation Study, Sergey M. Plis, Devon R. Hjelm, Ruslan Salakhutdinov, Elena A. Allen, Henry J. Bockholt, Jeffrey D. Long, Hans J. Johnson, Jane S. Paulsen, Jessica A. Turner, Vince D. Calhoun

Neuroscience Institute Faculty Publications

Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager’s toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building …

Interdisciplinary Perspectives On The Development, Integration, And Application Of Cognitive Ontologies, Janna Hastings, Gwen A. Frishkoff, Barry Smith, Mark Jensen, Russell A. Poldrack, Jane Lomax, Anita Bandrowski, Fahim Imam, Jessica Turner, Maryann E. Martone

Neuroscience Institute Faculty Publications

We discuss recent progress in the development of cognitive ontologies and summarize three challenges in the coordinated development and application of these resources. Challenge 1 is to adopt a standardized definition for cognitive processes. We describe three possibilities and recommend one that is consistent with the standard view in cognitive and biomedical sciences. Challenge 2 is harmonization. Gaps and conflicts in representation must be resolved so that these resources can be combined for mark-up and interpretation of multi-modal data. Finally, Challenge 3 is to test the utility of these resources for large- scale annotation of data, search and query, and …

Hidden Synaptic Differences In A Neural Circuit Underlie Differential Behavioral Susceptibility To A Neural Injury, Akira Sakurai, Arianna Tamvacakis, Paul Katz

Neuroscience Institute Faculty Publications

Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animals within the neural circuit underlying swimming behavior had no behavioral relevance under normal conditions but caused differential vulnerability of the behavior to a particular brain lesion. The extent of motor impairment correlated with the site of spike initiation in a specific neuron in the neural circuit, which was determined by the strength of an …

Hidden Synaptic Differences In A Neural Circuit Underlie Differential Behavioral Susceptibility To A Neural Injury, Akira Sakurai, Arianna Tamvacakis, Paul S. Katz

Neuroscience Institute Faculty Publications

Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animals within the neural circuit underlying swimming behavior had no behavioral relevance under normal conditions but caused differential vulnerability of the behavior to a particular brain lesion. The extent of motor impairment correlated with the site of spike initiation in a specific neuron in the neural circuit, which was determined by the strength of an …

Sharing Privacy-Sensitive Access To Neuroimaging And Genetics Data: A Review And Preliminary Validation, Anand D. Sarwate, Sergey M. Plis, Jessica A. Turner, Mohammad R. Arbabshirani, Vince D. Calhoun

Neuroscience Institute Faculty Publications

The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; …

Sharing Privacy-Sensitive Access To Neuroimaging And Genetics Data: A Review And Preliminary Validation, Anand D. Sarwate, Sergey M. Plis, Jessica Turner, Mohammad R. Arbabshirani, Vince D. Calhoun

Neuroscience Institute Faculty Publications

The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; …

Key Bifurcations Of Bursting Polyrhythms In 3-Cell Central Pattern Generators, Jeremy Wojcik, Justus Schwabedal, Robert Clewley, Andrey L. Shilnikov

Neuroscience Institute Faculty Publications

We identify and describe the key qualitative rhythmic states in various 3-cell network motifs of a multifunctional central pattern generator (CPG). Such CPGs are neural microcircuits of cells whose synergetic interactions produce multiple states with distinct phase-locked patterns of bursting activity. To study biologically plausible CPG models, we develop a suite of computational tools that reduce the problem of stability and existence of rhythmic patterns in networks to the bifurcation analysis of fixed points and invariant curves of a Poincare´ return maps for phase lags between cells. We explore different functional possibilities for motifs involving symmetry breaking and heterogeneity. This …

Sexually Dimorphic Role For Vasopressin In The Development Of Social Play, Matthew J. Paul, Joseph I. Terranova, Clemens K. Probst, Elaine K. Murray, Nafissa I. Ismail, Geert De Vries

Neuroscience Institute Faculty Publications

Despite the well-established role of arginine vasopressin (AVP) in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of …

Nih Initiative To Balance Sex Of Animals In Preclinical Studies: Generative Questions To Guide Policy, Implementation, And Metrics, Louise Mccullough, Geert De Vries, Virginia M. Miller, Jill Becker, Kathryn Sandberg, Margaret M. Mccarthy

Neuroscience Institute Faculty Publications

In May of 2014, the NIH Director together with the Director of the Office of Research on Women’s Health announced plans to take a multi-dimensional approach to address the over reliance on male cells and animals in preclinical research. The NIH is engaging the scientific community in the development of policies to improve the sex balance in research. The present, past, and future presidents of the Organization for the Study of Sex Differences, in order to encourage thoughtful discussion among scientists, pose a series of questions to generate ideas in three areas: 1. research strategies, 2. educational strategies, and 3. …

The Effects Of Perinatal Testosterone Exposure On The Dna Methylome Of The Mouse Brain Are Late-Emerging, Negar M. Ghahramani, Tuck Ngun, Pao-Yang Chen, Yuan Tian, Sangitha Krishnan, Stephanie Muir, Liudmilla Rubbi, Arthur P. Arnold, Geert De Vries, Nancy Forger, Matteo Pellegrini, Eric Vilain

Neuroscience Institute Faculty Publications

Background

The biological basis for sex differences in brain function and disease susceptibility is poorly understood. Examining the role of gonadal hormones in brain sexual differentiation may provide important information about sex differences in neural health and development. Permanent masculinization of brain structure, function, and disease is induced by testosterone prenatally in males, but the possible mediation of these effects by long-term changes in the epigenome is poorly understood.

Methods

We investigated the organizational effects of testosterone on the DNA methylome and transcriptome in two sexually dimorphic forebrain regions—the bed nucleus of the stria terminalis/preoptic area and the striatum. To …

The Rise Of Large-Scale Imaging Studies In Psychiatry, Jessica Turner

Neuroscience Institute Faculty Publications

From the initial arguments over whether 12 to 20 subjects were sufficient for an fMRI study, sample sizes in psychiatric neuroimaging studies have expanded into the tens of thousands. These large-scale imaging studies fall into several categories, each of which has specific advantages and challenges. The different study types can be grouped based on their level of control: meta-analyses, at one extreme of the spectrum, control nothing about the imaging protocol or subject selection criteria in the datasets they include, On the other hand, planned multi-site mega studies pour intense efforts into strictly having the same protocols. However, there are …

Poor Receptive Joint Attention Skills Are Associated With Atypical Gray Matter Asymmetry In The Posterior Superior Temporal Gyrus Of Chimpanzees (Pan Troglodytes), William D. Hopkins, Maria Misiura, Lisa A. Reamer, Jennifer A. Schaeffer, Mary C. Mareno, Steven J. Schapiro

Neuroscience Institute Faculty Publications

Clinical and experimental data have implicated the posterior superior temporal gyrus as an important cortical region in the processing of socially relevant stimuli such as gaze following, eye direction, and head orientation. Gaze following and responding to different socio-communicative signals is an important and highly adaptive skill in primates, including humans. Here, we examined whether individual differences in responding to socio- communicative cues was associated with variation in either gray matter (GM) volume and asymmetry in a sample of chimpanzees. Magnetic resonance image scans and behavioral data on receptive joint attention (RJA) was obtained from a sample of 191 chimpanzees. …

Genetic Influences On Receptive Joint Attention In Chimpanzees (Pan Troglodytes), William D. Hopkins, Alaine C. Keebaugh, Lisa A. Reamer, Jennifer Schaefer, Steven J. Schapiro, Larry J. Young

Neuroscience Institute Faculty Publications

Despite their genetic similarity to humans, our understanding of the role of genes on cognitive traits in chimpanzees remains virtually unexplored. Here, we examined the relationship between genetic variation in the arginine vasopressin V1a receptor gene (AVPR1A) and social cognition in chimpanzees. Studies have shown that chimpanzees are polymorphic for a deletion in a sequence in the 59 flanking region of the AVPR1A, DupB, which contains the variable RS3 repetitive element, which has been associated with variation in social behavior in humans. Results revealed that performance on the social cognition task was significantly heritable. Furthermore, males with one DupB1 allele …

Neuroanatomical Domain Of The Foundational Model Of Anatomy Ontology, B Nolan Nichols, Jose Lv Mejino, Landon T. Detwiler, Trond T. Nilsen, Maryann E. Martone, Jessica Turner, Daniel L. Rubin, James F. Brinkley

Neuroscience Institute Faculty Publications

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 …

A Codimension-2 Bifurcation Controlling Endogenous Bursting Activity And Pulse-Triggered Responses Of A Neuron Model, William Halbert Barnett, Gennady Cymbalyuk

Neuroscience Institute Faculty Publications

The dynamics of individual neurons are crucial for producing functional activity in neuronal networks. An open question is how temporal characteristics can be controlled in bursting activity and in transient neuronal responses to synaptic input. Bifurcation theory provides a framework to discover generic mechanisms addressing this question. We present a family of mechanisms organized around a global codimension-2 bifurcation. The cornerstone bifurcation is located at the intersection of the border between bursting and spiking and the border between bursting and silence. These borders correspond to the blue sky catastrophe bifurcation and the saddle-node bifurcation on an invariant circle (SNIC) curves, …