rudyvdbrink/CitationDatabase huggingface dataset:
Cloning and molecular characterization of the orphan carrier protein Slc10a4: expression in cholinergic neurons of the rat central nervous system.
Neuroscience, 2008

We report on the cloning and molecular characterization of the rat carrier Slc10a4 and its cellular localization in the CNS by immunohistochemistry. Slc10a4 is the rat counterpart of the human orphan carrier SLC10A4, which was recently reported to be highly expressed in brain and placenta. Both carriers belong to the solute carrier family SLC10, formerly named the "sodium/bile acid cotransporter family." So SLC10A4/Slc10a4 has a phylogenetic relationship to the Na+/taurocholate cotransporting polypeptide Ntcp (Slc10a1) and the apical sodium-dependent bile acid transporter Asbt (Slc10a2). The rat Slc10a4 protein consists of 437 amino acids and exhibits a seven transmembrane domain topology with N(exo)/C(cyt)trans-orientation of the N- and C-terminal ends. Expression of the Slc10a4 protein was detected in motor regions of the spinal cord and rhombencephalon, as well as in mesopontine cholinergic neurons, the medial habenula, cholinergic areas of the forebrain, and the gut myenteric plexus. Co-localization studies with the cholinergic marker proteins choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and high-affinity choline transporter (CHT1) demonstrated expression of Slc10a4 in cholinergic neurons. Despite its close phylogenetic relationship to Ntcp, Slc10a4 showed no transport activity for the Ntcp substrates taurocholate, estrone-3-sulfate, dehydroepiandrosterone sulfate, and pregnenolone sulfate when expressed in HEK293 cells or Xenopus laevis oocytes. Slc10a4 also did not transport choline, which is a substrate of CHT1. Although the functional properties of Slc10a4 could not be elucidated in this study, Slc10a4 is regarded as a new marker protein for cholinergic neurons in the rat CNS.
Mind Bomb-Binding Partner RanBP9 Plays a Contributory Role in Retinal Development.
Molecules and cells, 2017

Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of
Regulating the transcriptomes that mediate the conversion of fibroblasts to various nervous system neural cell types.
Journal of cellular physiology, 2018

Our understanding of the mechanism of cell fate transition during the direct reprogramming of fibroblasts into various central nervous system (CNS) neural cell types has been limited by the lack of a comprehensive analysis on generated cells, independently and in comparison with other CNS neural cell types. Here, we applied an integrative approach on 18 independent high throughput expression data sets to gain insight into the regulation of the transcriptome during the conversion of fibroblasts into induced neural stem cells, induced neurons (iNs), induced astrocytes, and induced oligodendrocyte progenitor cells (iOPCs). We found common down-regulated genes to be mostly related to fibroblast-specific functions, and suggest their potential as markers for screening of the silencing of the fibroblast-specific program. For example, Tagln was significantly down-regulated across all considered data sets. In addition, we identified specific profiles of up-regulated genes for each CNS neural cell types, which could be potential markers for maturation and efficiency screenings. Furthermore, we identified the main TFs involved in the regulation of the gene expression program during direct reprogramming. For example, in the generation of iNs from fibroblasts, the Rest TF was the main regulator of this reprogramming. In summary, our computational approach for meta-analyzing independent expression data sets provides significant details regarding the molecular mechanisms underlying the regulation of the gene expression program, and also suggests potentially useful candidate genes for screening down-regulation of fibroblast gene expression profile, maturation, and efficiency, as well as candidate TFs for increasing the efficiency of the reprogramming process.
Methylphenidate restores novel object recognition in DARPP-32 knockout mice.
Behavioural brain research, 2013

Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate.
Efficacy of stimulus intensity increases and decreases as inhibitors of the acoustic startle response.
Psychophysiology, 2018

The human startle eyeblink response can be inhibited by a change in the stimulus environment briefly before the startling stimulus; both stimulus presentation (prepulse) and cessation of background sound (gap) can result in startle inhibition. More intense prepulses often result in greater inhibition, and this study (N = 53 college students) examined whether graded decreases in sound energy relative to a steady background noise (a "partial gap") would follow this same pattern of inhibition. Embedded in a 65 dB steady background noise were 100 dB white noise startle stimuli preceded at 120 ms on some trials by stimulus intensity increases or decreases of 5, 10, or 15 dB relative to background. Results showed that startle inhibition was graded by amount of change relative to background, such that greater increases or decreases resulted in greater inhibition. Also, increases were more effective startle inhibitors than decreases at equivalent levels of change from background. These results demonstrate that the neural centers responsible for startle inhibition are responsive to both increases and decreases in stimulus intensity, and are sensitive to amount of change, not simply whether a change occurs. These findings may have implications for the development of a screening method for a hearing disorder called tinnitus.
Sleep-related memory consolidation in the psychosis spectrum phenotype.
Neurobiology of learning and memory, 2020

Sleep and memory processing impairments range from mild to severe in the psychosis spectrum. Relationships between memory processing and sleep characteristics have been described for schizophrenia, including unaffected first-degree relatives, but they are less clear across other high-risk groups within the psychosis spectrum. In this study, we investigated high-risk individuals with accumulated risk-factors for psychosis and subthreshold symptoms. Out of 1898 screened individuals, 44 age- and sex-matched participants were sub-grouped into those with substantial environmental risk factors for psychosis and subthreshold psychotic symptoms (high-risk group) and those without these phenotypes (low-risk controls). Four groups (high/low risk, morning/evening training) were trained and tested in the laboratory for sustained attention, motor skill memory (finger-tapping task) and declarative memory (word-pair learning task) immediately after training, again after a night of EEG-recorded sleep at home or a period of daytime wakefulness, and again after 24 h from training. No differences in sustained attention or in memory consolidation of declarative and motor skill memory were found between groups for any time period tested. However, a group difference was found for rapid-eye movement (REM) sleep in relation to motor skill memory: the longer the total sleep time, particularly longer REM sleep, the greater the performance gain, which occurred only in high-risk individuals. In conclusion, our results suggest a gain in motor skill performance with sufficient sleep opportunity for longer REM sleep in high-risk individuals with subthreshold psychotic symptoms. Declarative memory did not benefit from sleep consolidation above or beyond that of the control group.
Validation of a UPDRS-/MDS-UPDRS-based definition of functional dependency for Parkinson's disease.
Parkinsonism & related disorders, 2020

Functional dependency in basic activities of daily living (ADLs) is a key outcome in Parkinson's disease (PD). We aimed to define dependency in PD, using the original and MDS versions of the Unified Parkinson's Disease Rating Scale (UPDRS).
Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth.
Molecular psychiatry, 2016

Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions.
Sodium channel epilepsies and neurodevelopmental disorders: from disease mechanisms to clinical application.
Developmental medicine and child neurology, 2020

Genetic variants in brain-expressed voltage-gated sodium channels (SCNs) have emerged as one of the most frequent causes of Mendelian forms of epilepsy and neurodevelopmental disorders (NDDs). This review explores the biological concepts that underlie sodium channel NDDs, explains their phenotypic heterogeneity, and appraises how this knowledge may inform clinical practice. We observe that excitatory/inhibitory neuronal expression ratios of sodium channels are important regulatory mechanisms underlying brain development, homeostasis, and neurological diseases. We hypothesize that a detailed understanding of gene expression, variant tolerance, location, and function, as well as timing of seizure onset can aid the understanding of how variants in SCN1A, SCN2A, SCN3A, and SCN8A contribute to seizure aetiology and inform treatment choice. We propose a model in which variant type, development-specific gene expression, and functions of SCNs explain the heterogeneity of sodium channel associated NDDs. Understanding of basic disease mechanisms and detailed knowledge of variant characteristics have increasing influence on clinical decision making, enabling us to stratify treatment and move closer towards precision medicine in sodium channel epilepsy and NDDs. WHAT THIS PAPER ADDS: Sodium-channel disorder heterogeneity is explained by variant-specific gene expression timing and function. Gene tolerance and location analyses aid sodium channel variant interpretation. Sodium-channel variant characteristics can contribute to clinical decision making.
Early-stage waves in the retinal network emerge close to a critical state transition between local and global functional connectivity.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

A novel, biophysically realistic model for early-stage, acetylcholine-mediated retinal waves is presented. In this model, neural excitability is regulated through a slow after-hyperpolarization (sAHP) operating on two different temporal scales. As a result, the simulated network exhibits competition between a desynchronizing effect of spontaneous, cell-intrinsic bursts, and the synchronizing effect of synaptic transmission during retinal waves. Cell-intrinsic bursts decouple the retinal network through activation of the sAHP current, and we show that the network is capable of operating at a transition point between purely local and global functional connectedness, which corresponds to a percolation phase transition. Multielectrode array recordings show that, at this point, the properties of retinal waves are reliably predicted by the model. These results indicate that early spontaneous activity in the developing retina is regulated according to a very specific principle, which maximizes randomness and variability in the resulting activity patterns.
What Underlies Political Polarization? A Manifesto for Computational Political Psychology.
Trends in cognitive sciences, 2019

Polarization is one of the biggest societal challenges of our time, yet its drivers are poorly understood. Here we propose a novel approach - computational political psychology - which uses behavioral tasks in combination with formal computational models to identify candidate cognitive processes underpinning susceptibility to polarized beliefs about political and societal issues.
Cortical Representations of Speech in a Multitalker Auditory Scene.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

The ability to parse a complex auditory scene into perceptual objects is facilitated by a hierarchical auditory system. Successive stages in the hierarchy transform an auditory scene of multiple overlapping sources, from peripheral tonotopically based representations in the auditory nerve, into perceptually distinct auditory-object-based representations in the auditory cortex. Here, using magnetoencephalography recordings from men and women, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in distinct hierarchical stages of the auditory cortex. Using systems-theoretic methods of stimulus reconstruction, we show that the primary-like areas in the auditory cortex contain dominantly spectrotemporal-based representations of the entire auditory scene. Here, both attended and ignored speech streams are represented with almost equal fidelity, and a global representation of the full auditory scene with all its streams is a better candidate neural representation than that of individual streams being represented separately. We also show that higher-order auditory cortical areas, by contrast, represent the attended stream separately and with significantly higher fidelity than unattended streams. Furthermore, the unattended background streams are more faithfully represented as a single unsegregated background object rather than as separated objects. Together, these findings demonstrate the progression of the representations and processing of a complex acoustic scene up through the hierarchy of the human auditory cortex.
Mesolimbic Dopamine Function Is Related to Salience Network Connectivity: An Integrative Positron Emission Tomography and Magnetic Resonance Study.
Biological psychiatry, 2019

A wide range of neuropsychiatric disorders, from schizophrenia to drug addiction, involve abnormalities in both the mesolimbic dopamine system and the cortical salience network. Both systems play a key role in the detection of behaviorally relevant environmental stimuli. Although anatomical overlap exists, the functional relationship between these systems remains unknown. Preclinical research has suggested that the firing of mesolimbic dopamine neurons may activate nodes of the salience network, but in vivo human research is required given the species-specific nature of this network.
Electrical Muscle Stimulation Accelerates Functional Recovery After Nerve Injury.
Neuroscience, 2020

Electrical muscle stimulation has been demonstrated to facilitate nerve regeneration and functional recovery, but the underlying mechanism remains only partially understood. In this study, we investigated the positive effect of electrical muscle stimulation following nerve injury and its molecular mechanisms of autophagy regulation. The sciatic nerves of Sprague-Dawley rats were transected and immediately repaired. Gastrocnemius muscles were electrically stimulated using surface electrodes. Motor functional recovery was assessed by gait analysis, nerve conduction examination and histological appearance of the target muscle. Axon regeneration was investigated by morphometric analysis. Western blotting and immunofluorescence staining were used to detect the expression of molecular biological changes in distal nerve stump. Ultrastructural features of the nerve were evaluated by transmission electron microscope. We found that axon regeneration and motor functional recovery were improved by electrical muscle stimulation. The number of autophagosomes and the expression of autophagy marker LC3-Ⅱ in distal nerve stump were increased while the level of autophagy substrate protein P62 was decreased following electrical muscle stimulation. Blockage of the autophagy flux by chloroquine (CQ) diminished the positive effect of electrical muscle stimulation on nerve injury. These results illustrated that electrical muscle stimulation accelerates axon regeneration and functional recovery through promoting autophagy flux in distal nerve segments following nerve injury and immediate repair (IR) by a so far unknown mechanism.
Promises, promises for neuroscience and law.
Current biology : CB, 2014

Stunning technical advances in the ability to image the human brain have provoked excited speculation about the application of neuroscience to other fields. The 'promise' of neuroscience for law has been touted with particular enthusiasm. Here, we contend that this promise elides fundamental conceptual issues that limit the usefulness of neuroscience for law. Recommendations for overcoming these challenges are offered.
Automatic processing of emotional stimuli in euthymic patients with bipolar disorder.
Journal of affective disorders, 2016

Biased information processing styles are a core feature of cognitive models of unipolar depression (UD). The manic-defence hypothesis (MDH) posits that UD and Bipolar Disorder (BD) are subject partially to the same underlying cognitive processes, which may act as putative vulnerability factors. Previous studies have used experimental paradigms as a way of measuring automatic (non-intentional) processing of emotional information in order to test the MDH with some studies providing some evidence for a negatively biased automatic processing of emotionally-relevant information in BD. However, most prior studies used supraliminal stimuli (i.e. presented above perceptual threshold). Based on the MDH we predicted that subliminally presented negative stimuli will affect performance of patients with BD differently than non-clinical participants, but similarly to what has been observed in prior studies with currently depressed patients.
A narrative review: The effects of opioids on sleep disordered breathing in chronic pain patients and methadone maintained patients.
The American journal on addictions, 2016

Opioids increase the risk for sleep disordered breathing (SDB), but there are few studies examining the prevalence and risk factors for SDB, specifically central sleep apnea (CSA), and obstructive sleep apnea (OSA) in chronic pain patients on opioids as well as methadone maintained patients (MMPs).
A dual but asymmetric role of the dorsal anterior cingulate cortex in response inhibition and switching from a non-salient to salient action.
NeuroImage, 2016

Response inhibition and salience detection are among the most studied psychological constructs of cognitive control. Despite a growing body of work, how inhibition and salience processing interact and engage regional brain activations remains unclear. Here, we examined this issue in a stop signal task (SST), where a prepotent response needs to be inhibited to allow an alternative, less dominant response. Sixteen adult individuals performed two versions of the SST each with 25% (SST25) and 75% (SST75) of stop trials. We posited that greater regional activations to the infrequent trial type in each condition (i.e., to stop as compared to go trials in SST25 and to go as compared to stop trials in SST75) support salience detection. Further, successful inhibition in stop trials requires attention to the stop signal to trigger motor inhibition, and the stop signal reaction time (SSRT) has been used to index the efficiency of motor response inhibition. Therefore, greater regional activations to stop as compared to go success trials in association with the stop signal reaction time (SSRT) serve to expedite response inhibition. In support of an interactive role, the dorsal anterior cingulate cortex (dACC) increases activation to salience detection in both SST25 and SST75, but only mediates response inhibition in SST75. Thus, infrequency response in the dACC supports motor inhibition only when stopping has become a routine. In contrast, although the evidence is less robust, the pre-supplementary motor area (pre-SMA) increases activity to the infrequent stimulus and supports inhibition in both SST25 and SST75. These findings clarify a unique role of the dACC and add to the literature that distinguishes dACC and pre-SMA functions in cognitive control.