rudyvdbrink/CitationDatabase huggingface dataset:
Schizophrenia and Corollary Discharge: A Neuroscientific Overview and Translational Implications.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 2019

Corollary discharge mechanism refers to the suppression of sensory consequences of self-generated actions; a process that serves to distinguish between self and non-self based on discrimination of origination of action. It explains, say for example, why we cannot tickle ourselves. This review discusses how corollary discharge model is an essential neural integration mechanism central to the motor functioning of animal kingdom. In this article, research conducted in the field of corollary discharge has been reviewed to understand the neuroanatomical and neurophysiological basis of corollary discharge and gain insight into the biochemical basis of its dysfunction. This review article also explores the role of corollary discharge and its dysfunction in the presentation of symptoms of schizophrenia, discussing the findings from corollary discharge studies on schizophrenia population. Lastly, the link between schizophrenia psychopathology and corollary discharge dysfunction has been highlighted, and an attempt has been made to establish a case for correction of corollary discharge deficit in schizophrenia through neuromodulation.
Adaptive, behaviorally gated, persistent encoding of task-relevant auditory information in ferret frontal cortex.
Nature neuroscience, 2010

Top-down signals from frontal cortex are thought to be important in cognitive control of sensory processing. To explore this interaction, we compared activity in ferret frontal cortex and primary auditory cortex (A1) during auditory and visual tasks requiring discrimination between classes of reference and target stimuli. Frontal cortex responses were behaviorally gated, selectively encoded the timing and invariant behavioral meaning of target stimuli, could be rapid in onset, and sometimes persisted for hours following behavior. These results are consistent with earlier findings in A1 that attention triggered rapid, selective, persistent, task-related changes in spectrotemporal receptive fields. Simultaneously recorded local field potentials revealed behaviorally gated changes in inter-areal coherence that were selectively modulated between frontal cortex and focal regions of A1 that were responsive to target sounds. These results suggest that A1 and frontal cortex dynamically establish a functional connection during auditory behavior that shapes the flow of sensory information and maintains a persistent trace of recent task-relevant stimulus features.
Interference of lateralized distractors on arithmetic problem solving: a functional role for attention shifts in mental calculation.
Psychological research, 2016

Solving arithmetic problems has been shown to induce shifts of spatial attention in simple probe-detection tasks, subtractions orienting attention to the left side and additions to the right side of space. Whether these attentional shifts constitute epiphenomena or are critically linked to the calculation process is still unknown. In the present study, we investigate participants' performance on addition and subtraction solving while they have to detect central or lateralized targets. The results show that lateralized distractors presented in the hemifield congruent to the operation to be solved interfere with arithmetical solving: participants are slower to solve subtractions or additions when distractors are located on the left or on the right, respectively. These results converge with previous data to show that attentional shifts underlie not only number processing but also mental arithmetic. They extend them as they reveal the reverse effect of the one previously reported by showing that inducing attention shifts interferes with the solving of arithmetic problems. They also demonstrate that spatial attentional shifts are part of the calculation procedure of solving mentally arithmetic problems. Their functional role is to access, from the first operand, the representation of the result in a direction congruent to the operation.
Mitochondrial DNA toxicity compromises mitochondrial dynamics and induces hippocampal antioxidant defenses.
DNA repair, 2011

Mitochondria are highly dynamic organelles that can be actively transported within the cell to satisfy local requirements. They are vital for providing cellular energy, but are also an important endogenous source of reactive oxygen species. The distribution of mitochondria is particularly important for neurons because of the morphological complexity of these cells, and because neural processing is metabolically expensive. Defects in mitochondrial distribution, observed in several neurodegenerative diseases, can result in synaptic dysfunction. We have generated transgenic mice expressing an enzyme in forebrain neurons that causes mitochondrial DNA (mtDNA) damage in the form of abasic-sites, creating mtDNA toxicity. Here, we report that mitochondrial distribution is disturbed in hippocampal neurons of these mice. Moreover, mtDNA copy number and mitochondrial transcription are reduced, and oxidative stress is increased. There is also a loss of receptors at excitatory glutamatergic synapses in the dentate gyrus, and the size of the postsynaptic density in this region is abnormal. We speculate that the loss of synaptic mitochondria caused by accumulation in the neuronal cell body contributes to the observed synaptic abnormalities, as well as the overall loss of mtDNA and diminished mitochondrial transcription. Collectively, these changes lead to mitochondria with reduced function and increased oxidative stress.
Aberrant Cerebellar Resting-State Functional Connectivity Related to Reading Performance in Struggling Readers.
Developmental science, 2021

Reading is a critical neurodevelopmental skill for school-aged children, which requires a distributed network of brain regions including the cerebellum. However, we do not know how functional connectivity between the cerebellum and other brain regions contributes to reading. Here we used resting-state functional connectivity to understand the cerebellum's role in decoding, reading speed, and comprehension in a group of struggling readers (RD) and a group of adolescents and children with typical reading abilities (TD). We observed an increase in functional connectivity between the sensorimotor network and the left angular gyrus, left lateral occipital cortex, and right inferior frontal gyrus in the RD group relative to the TD group. Additionally, functional connectivity between the cerebellum network and the precentral gyrus was decreased and was related to reading fluency in the RD group. Seed-based analysis revealed increased functional connectivity between crus 1, lobule 6, and lobule 8 of the cerebellum and brain regions related to the default mode network and the motor system for the RD group. We also found associations between reading performance and the functional connectivity between lobule 8 of the cerebellum and the left angular gyrus for both groups, with stronger relationships in the TD group. Specifically, the RD group displayed a positive relationship between functional connectivity, whereas the TD group displayed the opposite relationship. These results suggest that the cerebellum is involved in multiple components of reading performance and that functional connectivity differences observed in the RD group may contribute to poor reading performance.
Adolescent brain maturation is necessary for adult-typical mesocorticolimbic responses to a rewarding social cue.
Developmental neurobiology, 2013

The interpretation of social cues must change during adolescence in order to promote appropriate social interactions in adulthood. For example, adult, but not juvenile, male Syrian hamsters find female pheromones contained in vaginal sections (VS) rewarding, and only adult hamsters engage in sexual behavior with a receptive female. We previously demonstrated that the rewarding value of VS is both testosterone- and dopamine-dependent. Additionally, VS induces Fos expression throughout the mesocorticolimbic circuit in adult but not juvenile hamsters. In this study, we determined whether or not treatment of juvenile male hamsters with testosterone is sufficient to promote adult-like neural responses to VS. Juvenile and adult male hamsters were gonadectomized and given empty or testosterone-filled subcutaneous capsules for 1 week. Hamsters were then exposed to either clean or VS-containing mineral oil on their nares, and brains were collected 1 h later for immunohistochemistry to visualize Fos and tyrosine hydroxylase immunoreactive cells. Testosterone treatment failed to promote adult-typical patterns of Fos expression in juvenile hamsters; indeed, in some brain regions, juveniles exposed to VS expressed less Fos compared to age-matched controls while, as expected, adults exposed to VS expressed greater Fos compared to age-matched controls. Age-related changes in tyrosine hydroxylase expression were also observed. These data indicate that testosterone cannot activate the adult-typical pattern of Fos expression in response to female social cues in prepubertal males, and that additional neural maturation during adolescence is required for adult-typical mesocorticolimbic responses to female pheromones.
Genetic Relationships Between Ethanol-Induced Conditioned Place Aversion and Other Ethanol Phenotypes in 15 Inbred Mouse Strains.
Brain sciences, 2019

The genetic relationships between different behaviors used to index the aversive effects of ethanol are unknown. To address this issue, ethanol-induced conditioned place aversion (CPA) was tested in a genetically diverse panel of 15 inbred mouse strains. Mice were exposed to an unbiased place conditioning procedure using ethanol doses of 0, 2, or 4 g/kg; all injections were given immediately after 5-min exposure to distinctive tactile cues. There were dose-dependent effects of ethanol on CPA and on the change in pre-injection activity rates between the first and last conditioning trials. Most strains (80%) developed CPA, demonstrating the generalizability of this behavior. Moreover, genotype had significant effects on CPA magnitude and locomotor activity rates. Strain means from this study and previously published studies were then used to examine genetic correlations. These analyses showed significant genetic correlations between CPA and ethanol intake/preference, conditioned taste aversion, and drug withdrawal (but not blood ethanol concentration or conditioned place preference), supporting the idea of commonality in the genes underlying CPA and each of these behaviors. The overall pattern of findings is consistent with previous data suggesting that genetic differences in sensitivity to ethanol's aversive effects play a role in determining strain differences in ethanol drinking. The broader implication is that individuals who are more sensitive to the aversive effects of ethanol may be protected from developing the excessive drinking behaviors characteristic of alcohol use disorders.
Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities.
Journal of neuropathology and experimental neurology, 2018

Mitochondrial diseases (MDs) result from alteration of the mitochondrial respiratory chain (MRC) function. Despite the prevalence of MDs in the population, the paucity of animal models available limits the understanding of these disorders. Mutations in SDHA, a gene that codes for the alpha subunit of succinate dehydrogenase (SDH), can cause some forms of MD. SDHA is a crucial contributor to MRC function. In order to expand the range of MD animal models available, we attempted to generate a Sdha knockout rat. Since homozygous Sdha-/- rats could neither be identified in newborn litters, nor as early as embryonic day 14, we evaluated wild-type (WT) and heterozygous Sdha+/- genotypes. No differences in behavioral, biochemical, or molecular evaluations were observed between WT and Sdha+/- rats at 6 weeks or 6 months of age. However, 30% of Sdha+/- rats displayed mild muscle fiber atrophy with rare fibers negative for cytochrome oxidase and SDH on histochemical staining. Collectively, our data provide additional evidence that modeling SDH mutations in rodents may be challenging due to animal viability, and heterozygous rats are insufficiently symptomatic at a phenotypic and molecular level to be of significant use in the study of SDH deficiency.
Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain.
Molecular neurobiology, 2019

Pain affects both sensory and emotional aversive responses, often provoking depression and anxiety-related conditions when it becomes chronic. As the opioid receptors in the locus coeruleus (LC) have been implicated in pain, stress responses, and opioid drug effects, we explored the modifications to LC opioid neurotransmission in a chronic constriction injury (CCI) model of short- and long-term neuropathic pain (7 and 30 days after nerve injury). No significant changes were found after short-term CCI, yet after 30 days, CCI provoked an up-regulation of cAMP (cyclic 5'-adenosine monophosphate), pCREB (phosphorylated cAMP response element binding protein), protein kinase A, tyrosine hydroxylase, and electrical activity in the LC, as well as enhanced c-Fos expression. Acute mu opioid receptor desensitization was more intense in these animals, measured as the decline of the peak current caused by [Met5]-enkephalin and the reduction of forskolin-stimulated cAMP produced in response to DAMGO. Sustained morphine treatment did not markedly modify certain LC parameters in CCI-30d animals, such as [Met5]-enkephalin-induced potassium outward currents or burst activity and c-Fos rebound after naloxone precipitation, which may limit the development of some typical opioid drug-related adaptations. However, other phenomena were impaired by long-term CCI, including the reduction in forskolin-stimulated cAMP accumulation by DAMGO after naloxone precipitation in morphine dependent animals. Overall, this study suggests that long-term CCI leads to changes at the LC level that may contribute to the anxiodepressive phenotype that develops in these animals. Furthermore, opioid drugs produce complex adaptations in the LC in this model of chronic neuropathic pain.
The epidemiology of paediatric head injuries: data from a referral centre in Victoria, Australia.
Journal of paediatrics and child health, 2009

Currently, there are no population-based or hospital-based studies on the full spectrum of paediatric head injuries (HIs) in Australia. We set out to provide detailed information on the incidence rates, causes and clinical management of all severities of HI in children and adolescents at an Australian tertiary referral centre using emergency department (ED) and admission data as a basis for further investigations and prevention efforts.
Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities.
Developmental biology, 2019

Inverse gradients of transcriptional repressors antagonize the transcriptional effector response to morphogens. However, the role of such inverse regulation might not manifest solely from lack of repressors. Sonic hedgehog (Shh) patterns the forebrain by being expressed ventrally; however, absence of antagonizing Gli3 repressor paradoxically cause insufficient pathway activation. Interestingly, lack of the primary cilia-localized G-protein-coupled receptor, Gpr161 increases Shh signaling in the mouse neural tube from coordinated lack of Gli3 repressor and Smoothened-independent activation. Here, by deleting Gpr161 in mouse neuroepithelial cells and radial glia at early mid-gestation we detected derepression of Shh signaling throughout forebrain, allowing determination of the pathophysiological consequences. Accumulation of cerebrospinal fluid (hydrocephalus) was apparent by birth, although usual causative defects in multiciliated ependymal cells or aqueduct were not seen. Rather, the ventricular surface was expanded (ventriculomegaly) during embryogenesis from radial glial overproliferation. Cortical phenotypes included polymicrogyria in the medial cingulate cortex, increased proliferation of intermediate progenitors and basal radial glia, and altered neocortical cytoarchitectonic structure with increased upper layer and decreased deep layer neurons. Finally, periventricular nodular heterotopia resulted from disrupted neuronal migration, while the radial glial scaffold was unaffected. Overall, suppression of Shh pathway during early mid-gestation prevents ventricular overgrowth, and regulates cortical gyration and neocortical/periventricular cytoarchitecture.
Mechanisms of implementing public health interventions: a pooled causal mediation analysis of randomised trials.
Implementation science : IS, 2018

The World Health Organization recommends that nations implement evidence-based nutritional guidelines and policies in settings such as schools and childcare services to improve public health nutrition. Understanding the causal mechanism by which implementation strategies exert their effects could enhance guideline implementation. The aim of this study was to assess the mechanisms by which implementation strategies improved schools and childcare services' adherence to nutrition guidelines.
Genomics and bioinformatics of Parkinson's disease.
Cold Spring Harbor perspectives in medicine, 2012

Within the last two decades, genomics and bioinformatics have profoundly impacted our understanding of the molecular mechanisms of Parkinson's disease (PD). From the description of the first PD gene in 1997 until today, we have witnessed the emergence of new technologies that have revolutionized our concepts to identify genetic mechanisms implicated in human health and disease. Driven by the publication of the human genome sequence and followed by the description of detailed maps for common genetic variability, novel applications to rapidly scrutinize the entire genome in a systematic, cost-effective manner have become a reality. As a consequence, about 30 genetic loci have been unequivocally linked to the pathogenesis of PD highlighting essential molecular pathways underlying this common disorder. Herein we discuss how neurogenomics and bioinformatics are applied to dissect the nature of this complex disease with the overall aim of developing rational therapeutic interventions.
Mapping repetition suppression of the N100 evoked response to the human cerebral cortex.
Biological psychiatry, 2011

Repetition suppression (RS) phenomena, such as those observed using paired-identical-stimulus (S1-S2) paradigms, likely reflect adaptive functions such as habituation and, more specifically, sensory gating.
Abnormal function of monoamine oxidase-A in comorbid major depressive disorder and cardiovascular disease: pathophysiological and therapeutic implications (review).
Molecular medicine reports, 2012

The association between major depressive disorder (MDD) and cardiovascular disease (CVD) is among the best described medical comorbidities. The presence of MDD increases the risk of cardiac admissions and mortality and increases healthcare costs in patients with CVD, and similarly, CVD affects the course and outcome of MDD. The potential shared biological mechanisms involved in these comorbid conditions are not well known. However, the enzyme monoamine oxidase-A (MAO-A), which has a key role in the degradation of catecholamines, has been associated with the pathophysiology and therapeutics of both MDD and CVD. Increased MAO-A activity results in the dysregulation of downstream targets of this enzyme and thus affects the pathophysiology of the two diseases. These deleterious effects include altered noradrenaline turnover, with a direct elevation in oxidative stress parameters, as well as increased platelet activity and cytokine levels. These effects were shown to be reversed by MAO inhibitors. Here, a model describing a key role for the MAO-A in comorbid MDD and CVD is proposed, with focus on the shared pathophysiological mechanisms and the potential therapeutic relevance of agents targeting this enzyme.
Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Perisomatic inhibition from basket cells plays an important role in regulating pyramidal cell output. Two major subclasses of CA1 basket cells can be identified based on their expression of either cholecystokinin (CCK) or parvalbumin. This study examined their fates in the mouse pilocarpine model of temporal lobe epilepsy. Overall, immunohistochemical labeling of GABAergic boutons in the pyramidal cell layer of CA1 was preserved in the mouse model. However, CCK-labeled boutons in this layer were chronically reduced, whereas parvalbumin-containing boutons were conserved. Immunohistochemistry for cannabinoid receptor 1 (CB(1)), another marker for CCK-containing basket cells, also labeled fewer boutons in pilocarpine-treated mice. Hours after status epilepticus, electron microscopy revealed dark degenerating terminals in the pyramidal cell layer with lingering CCK and CB(1) immunoreactivity. In mice with recurrent seizures, carbachol-induced enhancement of spontaneous IPSCs (sIPSCs) originating from CCK-containing basket cells was accordingly reduced in CA1 pyramidal cells. By suppressing sIPSCs from CCK-expressing basket cells, a CB(1) agonist reverted the stimulatory effects of carbachol in naive mice to levels comparable with those observed in cells from epileptic mice. The agatoxin-sensitive component of CA1 pyramidal cell sIPSCs from parvalbumin-containing interneurons was increased in pilocarpine-treated mice, and miniature IPSCs were reduced, paralleling the decrease in CCK-labeled terminals. Altogether, the findings are consistent with selective reduction in perisomatic CA1 pyramidal cell innervation from CCK-expressing basket cells in mice with spontaneous seizures and a greater reliance on persisting parvalbumin innervation. This differential alteration in inhibition may contribute to the vulnerability of the network to seizure activity.
Robust short-latency perisomatic inhibition onto neocortical pyramidal cells detected by laser-scanning photostimulation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

Inhibitory connectivity onto neocortical pyramidal cells was mapped using LSPS (laser-scanning photostimulation/glutamate uncaging). The average onset latency of IPSCs was shorter than that of EPSCs recorded in the same cells, indicating a specific mechanism for rapid network recruitment of inhibition. The majority of strong inhibitory synaptic inputs originated within 300 mum of the recorded cell's soma, had onset latencies between 4 and 10 ms, and high amplitude [short-latency IPSCs (slIPSCs)]. slIPSCs were GABA(A) receptor- mediated chloride currents that were evoked in an all-or-none manner. We tested whether slIPSCs resulted from somatic depolarization of presynaptic interneurons or from direct excitation of inhibitory presynaptic terminals via kainate receptors. Our evidence supports the former hypothesis: (1) slIPSCs had similar sensitivity to kainate and AMPA receptor blockers as electrically evoked EPSCs. (2) slIPSCs frequently had an notched rising phase suggestive of summated IPSCs resulting from repetitive firing of presynaptic neurons. (3) Latencies and interevent intervals were consistent with spike latencies and interspike intervals in fast-spiking (FS) interneurons. (4) slIPSCs were frequently evoked at spots where the recorded cell was also excited directly, but approximately 15% of spots from which slIPSCs were evoked did not overlap with the recorded neuron's cell body. We propose that slIPSCs from FS interneurons represent a pool of powerful inhibitory signals that can be recruited by local excitation. Because of their magnitude, progressive recruitment, and short latency, slIPSCs are a effective mechanism of regulating excitability in neocortical circuits.