Neuroscience and Neurobiology Commons^™

Photoreceptor Phosphodiesterase (Pde6): Activation And Inactivation Mechanisms During Visual Transduction In Rods And Cones, Rick H. Cote

Faculty Publications

Rod and cone photoreceptors of the vertebrate retina utilize cGMP as the primary

intracellular messenger for the visual signaling pathway that converts a light stimulus into an electrical response. cGMP metabolism in the signal-transducing photoreceptor outer segment reflects the balance of cGMP synthesis (catalyzed by guanylyl cyclase) and degradation (catalyzed by the photoreceptor phosphodiesterase, PDE6). Upon light stimulation, rapid activation of PDE6 by the heterotrimeric G-protein (transducin) triggers a dramatic drop in cGMP levels that lead to cell hyperpolarization. Following cessation of the light stimulus, the lifetime of activated PDE6 is also precisely regulated by additional processes. This review summarizes …

Photoreceptor Phosphodiesterase (Pde6): Structure, Regulatory Mechanisms, And Implications For Treatment Of Retinal Diseases, Rick H. Cote, Richa Gupta, Michael J. Irwin, Xin Wang

Faculty Publications

The photoreceptor phosphodiesterase (PDE6) is a member of large family of Class I phosphodiesterases responsible for hydrolyzing the second messengers cAMP and cGMP. PDE6 consists of two catalytic subunits and two inhibitory subunits that form a tetrameric protein. PDE6 is a peripheral membrane protein that is localized to the signaling-transducing compartment of rod and cone photoreceptors. As the central effector enzyme of the G-protein coupled visual transduction pathway, activation of PDE6 catalysis causes in a rapid decrease in cGMP levels that results in closure of cGMP-gated ion channels in the photoreceptor plasma membrane. Because of its importance in the phototransduction …

Comparative Efficacies Of Calmare Therapy And Transcutaneous Electrical Nerve Stimulation In Randomized Peripheral Neuropathy Subjects With Resting State Fmri Monitoring, Ty A. Bodily, Logan Edvalson, Jordan B. Peacock, Zack M. Bradshaw, Carson Hart, Cameron Ernst, Samuel Biggs, David D. Busath

Faculty Publications

Clinical reports of Calmare protocol efficacy suggest enhanced durability compared to TENS and the possibility changes in resting fMRI connectivity. The objective was to compare peripheral neuropathy pain relief and resting fMRI changes with Calmare and TENS treatments. Randomized double-blind trials performed in August 2015 and between August 2016 and November 2017, with 18 and 20 human peripheral neuropathy subjects, respectively. The initial trial examined effects of a single session while the latter trial examined the effects of a course of ten treatment sessions on consecutive weekdays. fMRI scans were examined for changes in blood flow correlations and connectivity. Subjective …

Developing Outreach Events That Impact Underrepresented Students: Are We Doing It Right?, Andrew J. Gall, Peter J. Vollbrecht, Tristan Tobias

Faculty Publications

Many outreach programs share the common goals of serving underrepresented groups in STEM and improving public attitudes toward science. To meet these goals, scientists must find ways to both reach the appropriate audience and communicate the importance of science in meaningful and accessible ways. This requires careful consideration of the outreach method being used. Two common outreach methods include in‐school visits (scientist in the classroom) and science fairs or open houses. Here, we compare the effectiveness of these two outreach methods in meeting the goals of reaching underrepresented students and/or students with less initial interest in science. We have found …

Hydrogen Peroxide Triggers An Increase In Cell Surface Expression Of System XC− In Cultured Human Glioma Cells, Leah A. Chase, Mary Verheulen Kleyn, Natasha Schiller, Abby Goltz King, Guillermo Flores, Sasha Balcazar Engelsman, Christina Bowles, Sara Lang Smith, Anne E. Robinson, Jeffrey Rothstein

Faculty Publications

System x_c⁻ exchanges extracellular cystine for intracellular glutamate across the plasma membrane of many cell types. One of the physiological roles of System x_c⁻ is to provide cystine for synthesis of the antioxidant glutathione. Here we report that hydrogen peroxide (H₂O₂) triggers the translocation of System x_c⁻ to the plasma membrane within 10 min of the initial exposure. Specifically, we observed a three-fold increase in ³⁵S-L-cystine uptake following a 10 min exposure to 0.3 mM H₂O₂. This effect was dose-dependent with an EC₅₀ for …

Functional And Anatomical Variations In Retinorecipient Brain Areas In Arvicanthis Niloticus And Rattus Norvegicus: Implications For The Circadian And Masking Systems, Dorela D. Shuboni-Mulligan, Breyanna L. Cavanaugh, Anne Tonson, Erik M. Shapiro, Andrew J. Gall

Faculty Publications

Daily rhythms in light exposure influence the expression of behavior by entraining circadian rhythms and through its acute effects on behavior (i.e., masking). Importantly, these effects of light are dependent on the temporal niche of the organism; for diurnal organisms, light increases activity, whereas for nocturnal organisms, the opposite is true. Here we examined the functional and morphological differences between diurnal and nocturnal rodents in retinorecipient brain regions using Nile grass rats (Arvicanthis niloticus) and Sprague-Dawley (SD) rats (Rattus norvegicus), respectively. We established the presence of circadian rhythmicity in cFOS activation in retinorecipient brain regions in …

Melanopsin-Containing Iprgcs Are Resistant To Excitotoxic Injury And Maintain Functional Non-Image Forming Behaviors After Insult In A Diurnal Rodent Model, Garrett M. Fogo, Dorela D. Shuboni-Mulligan, Andrew J. Gall

Faculty Publications

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for the light signaling properties of non-image forming vision. Melanopsin-expressing ipRGCs project to retinorecipient brain regions involved in modulating circadian rhythms. Melanopsin has been shown to play an important role in how animals respond to light, including photoentrainment, masking (i.e., acute behavioral responses to light), and the pupillary light reflex (PLR). Importantly, ipRGCs are resistant to various forms of damage, including ocular hypertension, optic nerve crush, and excitotoxicity via N-methyl-D-aspartic acid (NMDA) administration. Although these cells are resistant to various forms of injury, the question still remains whether or …

Let It Rest: Sleep And Health As Positive Correlates Of Forgiveness Of Others And Self-Forgiveness, Loren Toussaint, Andrew J. Gall, Alyssa Cheadle, David R. Williams

Faculty Publications

Objective: The present study examined forgiveness of others, self-forgiveness, sleep, and health in a nationally representative sample of United States adults. It was hypothesised that sleep would mediate the associations of forgiveness of others and self-forgiveness with health.

Design: A nationally representative survey of 1,423 United States adults.

Main Outcome Measures: Measures included forgiveness of others, self-forgiveness, sleep quantity, sleep quality, psychological distress, life satisfaction, and self-rated physical health.

Results: Forgiveness of others (β = .20, p < .001) and self-forgiveness (β = .11, p < .01) were associated with sleep and forgiveness of others (β = .24, p < .001) and self-forgiveness (β = .27, p < .001) were associated with health. Sleep was associated with health (β = .45, p < .001) and also acted as a mediator of the associations of forgiveness of others (β = .09, p < .01) and self-forgiveness (β = .05, p < .01) with health.

Conclusions: Forgiveness of others and self-forgiveness may attenuate emotions such as anger, regret, and rumination and provide …

The Effects Of Ambient Temperature And Lighting Intensity On Wheel-Running Behavior In A Diurnal Rodent, The Nile Grass Rat (Arvicanthis Niloticus), Garrett M. Fogo, Alyssa M. Goodwin, Ohanes S. Khacherian, Brandi J. Ledbetter, Andrew J. Gall

Faculty Publications

Environmental conditions, such as the light-dark cycle and temperature, affect the display of circadian rhythmicity and locomotor activity patterns in mammals. Here, we tested the hypothesis that manipulating these environmental conditions would affect wheel-running activity patterns in a diurnal rodent, the Nile grass rat (Arvicanthis niloticus). Grass rats are diurnal in the field, however, a subset switch from a day-active pattern to a night-active pattern of activity after the introduction of a running wheel. The mechanism of this chronotype switch remains largely unknown. In the present study, grass rats were presented with running wheels in 12:12 light-dark conditions. First, subjects …

An Effective Model For Engaging Faculty And Undergraduate Students In Neuroscience Outreach With Middle Schoolers, Peter J. Vollbrecht, Riley S. Frenette, Andrew J. Gall

Faculty Publications

Engaging undergraduate students in science outreach events is critical for improving future communication between scientists and community members. Outreach events are opportunities for faculty and undergraduates to utilize active learning strategies to engage non-scientists in scientific questions and principles. Through careful design of outreach events, undergraduate students can practice science communication skills while reaching populations of the public that remain underserved and underrepresented in scientific fields. Here we describe a classroom outreach event designed to give a broad overview of the field of neuroscience to middle school students of all backgrounds by delivering the content in school, during school hours. …

An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen

Faculty Publications

We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …

'Neurophobia,' A Reply To Patterson, Peter A. Alces

Faculty Publications

No abstract provided.

Deep Long Short-Term Memory Structures Model Temporal Dependencies Improving Cognitive Workload Estimation, Ryan G. Hefron, Brett J. Borghetti, James C. Christensen, Christine M. Schubert Kabban

Faculty Publications

Using deeply recurrent neural networks to account for temporal dependence in electroencephalograph (EEG)-based workload estimation is shown to considerably improve day-to-day feature stationarity resulting in significantly higher accuracy (p < .0001) than classifiers which do not consider the temporal dependence encoded within the EEG time-series signal. This improvement is demonstrated by training several deep Recurrent Neural Network (RNN) models including Long Short-Term Memory (LSTM) architectures, a feedforward Artificial Neural Network (ANN), and Support Vector Machine (SVM) models on data from six participants who each perform several Multi-Attribute Task Battery (MATB) sessions on five separate days spread out over a month-long period. Each participant-specific classifier is trained on the first four days of data and tested using the fifth’s. Average classification accuracy of 93.0% is achieved using a deep LSTM architecture. These results represent a 59% decrease in error compared to the best previously published results for this dataset. This study additionally evaluates the significance of new features: all combinations of mean, variance, skewness, and kurtosis of EEG frequency-domain power distributions. Mean and variance are statistically significant features, while skewness and kurtosis are not. The overall performance of this approach is high enough to warrant evaluation for inclusion in operational systems.

Normal Behavioral Responses To Light And Darkness And The Pupillary Light Reflex Are Dependent Upon The Olivary Pretectal Nucleus In The Diurnal Nile Grass Rat, Andrew J. Gall, Ohanes S. Khacherian, Brandi Ledbetter, Sean P. Deats, Megan Luck, Laura Smale, Lily Yan, Antonio A. Nunez

Faculty Publications

The olivary pretectal nucleus (OPT) is a midbrain structure that receives reciprocal bilateral retinal projections, is involved in the pupillary light reflex, and connects reciprocally with the intergeniculate leaflet (IGL), a retinorecipient brain region that mediates behavioral responses to light pulses (i.e., masking) in diurnal Nile grass rats. Here, we lesioned the OPT and evaluated behavioral responses in grass rats to various lighting conditions, as well as their anxiety-like responses to light exposure. While control grass rats remained diurnal, grass rats with OPT lesions exhibited a more night-active pattern under 12h:12h light-dark (LD) conditions. However, when placed in constant darkness, …

Species Differences In Egocentric Navigation: The Effect Of Burrowing Ecology On A Spatial Cognitive Trait In Mice, Jason N. Bruck, Noah A. Allen, Kelsey E. Brass, Brian A. Horn, Polly Campbell

Faculty Publications

© 2017 The Association for the Study of Animal Behaviour Efficient navigation is a critical component of fitness for most animals. While most species use a combination of allocentric (external) and egocentric (internal) cues to navigate through their environment, subterranean environments present a unique challenge in that visually mediated allocentric cues are unavailable. The relationship between egocentric spatial cognition and species differences in ecology is surprisingly understudied. We used a maze-learning task to test for differences in egocentric navigation between two closely related species of mice, the eastern house mouse, Mus musculus musculus, and the mound-building mouse, Mus spicilegus. The …

Neuroscience Changes More Than You Can Think, Paul S. Davies, Peter A. Alces

Faculty Publications

In this Essay, we consider the contribution of a startling new book, Law & Neuroscience (L&N), by Owen Jones, Jeffrey Schall, and Francis Shen. It is a law school course book (a genre not often the focus of a scholarly review essay) that supports fundamental inquiry into the relationship between emerging neuroscientific insights and doctrinal conceptions in the law. We believe that the book shifts the paradigm and so may profoundly affect the course of normative evaluation of law. In this Essay, we trace and evaluate the “argument” of the book and suggest ways in which its contribution to the …

A Rare Case Of Erythema Elevatum Diutinum Presenting As Diffuse Neuropathy., G H. Nguyen, E L. Guo, D Norris

Faculty Publications

no abstract available

Consensus Paper: Cerebellar Development., K Leto, M Arancillo, Ebe Becker, A Chiang, Et Al.

Faculty Publications

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

The Contribution Of The Pineal Gland On Daily Rhythms And Masking In Diurnal Grass Rats, Arvicanthis Niloticus, Dorela D. Shuboni, Amna A. Agha, Thomas K. H. Groves, Andrew J. Gall

Faculty Publications

Melatonin is a hormone rhythmically secreted at night by the pineal gland in vertebrates. In diurnal mammals, melatonin is present during the inactive phase of the rest/activity cycle, and in primates it directly facilitates sleep and decreases body temperature. However, the role of the pineal gland for the promotion of sleep at night has not yet been studied in non-primate diurnal mammalian species. Here, the authors directly examined the hypothesis that the pineal gland contributes to diurnality in Nile grass rats by decreasing activity and increasing sleep at night, and that this could occur via effects on circadian mechanisms or …

Comparison Of Interactive Voice Response (Ivr) With Paper Administration Of Instruments To Assess Functional Status, Sexual Function, And Quality Of Life In Elderly Men., Rc Rosen, Aj Stephens-Shields, Gr Cunningham, D Cifelli, D Cella, Jt Farrar, E Barrett-Connor, Ce Lewis, M Pahor, X Hou, Pj Snyder

Faculty Publications

PURPOSE: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used. METHODS: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men = 65 years at each of two clinical sites. In …

Suprachiasmatic Nucleus And Subparaventricular Zone Lesions Disrupt Circadian Rhythmicity But Not Light-Induced Masking Behavior In Nile Grass Rats, Andrew J. Gall, Dorela D. Shuboni, Lily Yan, Antonio A. Nunez, Laura Smale

Faculty Publications

The ventral subparaventricular zone (vSPVZ) receives direct retinal input and influences the daily patterning of activity in rodents, making it a likely candidate for the mediation of acute behavioral responses to light (i.e., masking). We performed chemical lesions aimed at the vSPVZ of diurnal grass rats (Arvicanthis niloticus) using N-methyl-D,L-aspartic acid (NMA), a glutamate agonist. Following NMA lesions, we placed grass rats in various lighting conditions (e.g., 12:12 light-dark, constant dark, constant light); presented a series of light pulses at circadian times (CT) 6, 14, 18, and 22; and placed them in a 7-h ultradian cycle to assess behavioral masking. …

Ct-Based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring For Fracture Prediction In Metastatic Femoral Lesions., Ta Damron, A Nazarian, V Entezari, C Brown, W Grant, N Calderon, Et Al.

Faculty Publications

BACKGROUND: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy. QUESTIONS/PURPOSES: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and …

Explicit Time Deficit In Schizophrenia: Systematic Review And Meta-Analysis Indicate It Is Primary And Not Domain Specific., V Ciullo, G Spalletta, C Caltagirone, Re Jorge, F Piras

Faculty Publications

Although timing deficits are a robust finding in schizophrenia (SZ), the notion of a genuine time perception disorder in SZ is still being debated because distortions in timing might depend on neuropsychological deficits that are characteristics of the illness. Here we used meta-analytic methods to summarize the evidence of timing deficits in SZ and moderator analyses to determine whether defective timing in SZ arises from nontemporal sources or from defective time perception. PubMed Services, PsycNET, and Scopus were searched through March 2015, and all references in articles were investigated to find other relevant studies. Studies were selected if they included …

Binomial Regression With A Misclassified Covariate And Outcome., Sheng Luo, Wenyaw Chan, Michelle A Detry, Paul J Massman, R S. Doody

Faculty Publications

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach …

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies., Ms Siehr, Jl Noebels

Faculty Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Efficacy Of Psychosocial Interventions In Inducing And Maintaining Alcohol Abstinence In Patients With Chronic Liver Disease: A Systematic Review., A Khan, A Tansel, Dl White, Wt Kayani, Wt Bano, J Lindsay, Hb El-Serag, F Kanwal

Faculty Publications

BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), …

Eosinophilic Esophagitis In Children And Its Relationship With Parental Allergies: Texas Children's Hospital Experience., G Hiremath, D Byramji, A Pacheco, G Constantine, C Davis, R Shulman, A Olive

Faculty Publications

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. AIMS: To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. METHODS: Demographic and clinical information of 126 children (=18 years of age) with EoE was abstracted in a …

Glial Contributions To Neural Function And Disease., Mn Rasband

Faculty Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Effect Of Two-Year Caloric Restriction On Bone Metabolism And Bone Mineral Density In Non-Obese Younger Adults: A Randomized Clinical Trial., Dt Villareal, L Fontana, Sk Das, Et Al.

Faculty Publications

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1?±?1.7?kg/m(2) ), younger (age 37.9?±?7.2 years) adults were randomly assigned to 25% CR (CR group, n?=?143) or ad libitum (AL group, n?=?75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5?±?0.4 versus …

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb., Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …