rudyvdbrink/CitationDatabase huggingface dataset:
Independent anterograde transport and retrograde cotransport of domain components of myelinated axons.
The Journal of cell biology, 2020

Neurons are highly polarized cells organized into functionally and molecularly distinct domains. A key question is whether the multiprotein complexes that comprise these domains are preassembled, transported, and inserted as a complex or whether their components are transported independently and assemble locally. Here, we have dynamically imaged, in pairwise combinations, the vesicular transport of fluorescently tagged components of the nodes of Ranvier and other myelinated axonal domains in sensory neurons cultured alone or together with Schwann cells at the onset of myelination. In general, most proteins are transported independently in the anterograde direction. In contrast, there is substantial cotransport of proteins from distinct domains in the retrograde direction likely due to coendocytosis along the axon. Early myelination did not substantially change these patterns of transport, although it increased the overall numbers of axonal transport vesicles. Our results indicate domain components are transported in separate vesicles for local assembly, not as preformed complexes, and implicate endocytosis along axons as a mechanism of clearance.
The ovine motor cortex: A review of functional mapping and cytoarchitecture.
Neuroscience and biobehavioral reviews, 2017

In recent years, sheep (Ovis aries) have emerged as a useful animal model for neurological research due to their relatively large brain and blood vessel size, their cortical architecture, and their docile temperament. However, the functional anatomy of sheep brain is not as well studied as that of non-human primates, rodents, and felines. For example, while the location of the sheep motor cortex has been known for many years, there have been few studies of the somatotopy of the motor cortex and there were a range of discrepancies across them. The motivation for this review is to provide a definitive resource for studies of the sheep motor cortex. This work critically reviews the literature examining the organization of the motor cortex in sheep, utilizing studies that have applied direct electrical stimulation and histological methods A clearer understanding of the sheep brain will facilitate and progress the use of this species as a scientific animal model for neurological research.
Working memory-related changes in functional connectivity persist beyond task disengagement.
Human brain mapping, 2014

We examined whether altered connectivity in functional networks during working memory performance persists following conclusion of that performance, into a subsequent resting state. We conducted functional magnetic resonance imaging (fMRI) in 50 young adults during an initial resting state, followed by an N-back working memory task and a subsequent resting state, in order to examine changes in functional connectivity within and between the default-mode network (DMN) and the task-positive network (TPN) across the three states. We found that alterations in connectivity observed during the N-back task persisted into the subsequent resting state within the TPN and between the DMN and TPN, but not within the DMN. Further, both speed of working memory performance and TPN connectivity strength during the N-back task predicted connectivity strength in the subsequent resting state. Finally, DMN connectivity measured before and during the N-back task predicted individual differences in self-reported inattentiveness, but this association was not found during the post-task resting state. Together, these findings have important implications for models of how the brain recovers following effortful cognition, as well as for experimental designs using resting and task scans.
Novel halogenated derivates of JWH-018: Behavioral and binding studies in mice.
Neuropharmacology, 2015

JWH-018 is a synthetic CB1 and CB2 agonist illegally marketed as products named "Spice" or "herbal blend" for its psychoactive effects which are much higher than those produced by cannabis. In the last year, the European Monitoring Centre for Drugs and Drug Addiction reported to the Italian National Early Warning System the seizure of plant material containing new halogenated derivatives of JWH-018 (JWH-018 Cl and JWH-018 Br). The present study aimed to investigate the in vitro and in vivo activity of these two new synthetic cannabinoids in mice. In vitro competition binding experiments performed on mouse and human CB1 receptors revealed a high affinity and potency of the halogenated compounds. Synthetic cannabinoids (0.01-6 mg/kg i.p.) impaired motor activity and induced catalepsy in mice and their effects were more severe with respect to those evoked by Δ(9)-THC. Moreover, they increased the mechanical and thermal pain threshold and induced a marked hypothermia. It is interesting to note that whereas high doses of JWH-018 cause seizures, myoclonia and hyperreflexia, the halogenated compounds, in particular JWH-018Br, were less effective. Behavioral and neurological changes were prevented by the selective CB1 receptor antagonist AM 251. These data demonstrate for the first time that JWH-018 Cl and JWH-018 Br act similarly to JWH-018 while inducing less convulsive episodes and myoclonias. These data support the hypothesis that the halogenated compounds may have been introduced onto market to produce similar intoxicating effects as JWH-018 while causing less side effects.
Association of low perioperative prealbumin level and surgical complications in long-segment spinal fusion patients: A retrospective cohort study.
International journal of surgery (London, England), 2017

Spinal surgery places significant physiological and nutritional burden on the patient. Complications are common and can impact long-term clinical outcomes. Therefore, it is important to identify factors associated with perioperative complications to potentially mitigate the lasting effects on patient outcomes. The significant impact of malnutrition on surgical outcomes has been well established; however, there is a paucity of data in the spine literature. Our objective was to evaluate perioperative prealbumin level in patients undergoing long-segment spinal fusion and its relationship to surgical outcomes and complication rates.
Characterization of decision commitment rule alterations during an auditory change detection task.
Journal of neurophysiology, 2017

A critical component of decision making is determining when to commit to a choice. This involves stopping rules that specify the requirements for decision commitment. Flexibility of decision stopping rules provides an important means of control over decision-making processes. In many situations, these stopping rules establish a balance between premature decisions and late decisions. In this study we use a novel change detection paradigm to examine how subjects control this balance when invoking different decision stopping rules. The task design allows us to estimate the temporal weighting of sensory information for the decisions, and we find that different stopping rules did not result in systematic differences in that weighting. We also find bidirectional post-error alterations of decision strategy that depend on the type of error and effectively reduce the probability of making consecutive mistakes of the same type. This is a generalization to change detection tasks of the widespread observation of unidirectional post-error slowing in forced-choice tasks. On the basis of these results, we suggest change detection tasks as a promising paradigm to study the neural mechanisms that support flexible control of decision rules.
The Neural Basis for Response Latency in a Sensory-Motor Behavior.
Cerebral cortex (New York, N.Y. : 1991), 2020

We seek a neural circuit explanation for sensory-motor reaction times. In the smooth eye movement region of the frontal eye fields (FEFSEM), the latencies of pairs of neurons show trial-by-trial correlations that cause trial-by-trial correlations in neural and behavioral latency. These correlations can account for two-third of the observed variation in behavioral latency. The amplitude of preparatory activity also could contribute, but the responses of many FEFSEM neurons fail to support predictions of the traditional "ramp-to-threshold" model. As a correlate of neural processing that determines reaction time, the local field potential in FEFSEM includes a brief wave in the 5-15-Hz frequency range that precedes pursuit initiation and whose phase is correlated with the latency of pursuit in individual trials. We suggest that the latency of the incoming visual motion signals combines with the state of preparatory activity to determine the latency of the transient response that controls eye movement.
Experimental models to study intestinal microbes-mucus interactions in health and disease.
FEMS microbiology reviews, 2019

A close symbiotic relationship exists between the intestinal microbiota and its host. A critical component of gut homeostasis is the presence of a mucus layer covering the gastrointestinal tract. Mucus is a viscoelastic gel at the interface between the luminal content and the host tissue that provides a habitat to the gut microbiota and protects the intestinal epithelium. The review starts by setting up the biological context underpinning the need for experimental models to study gut bacteria-mucus interactions in the digestive environment. We provide an overview of the structure and function of intestinal mucus and mucins, their interactions with intestinal bacteria (including commensal, probiotics and pathogenic microorganisms) and their role in modulating health and disease states. We then describe the characteristics and potentials of experimental models currently available to study the mechanisms underpinning the interaction of mucus with gut microbes, including in vitro, ex vivo and in vivo models. We then discuss the limitations and challenges facing this field of research.
Repurposing Domperidone in Secondary Progressive Multiple Sclerosis: A Simon 2-Stage Phase 2 Futility Trial.
Neurology, 2021

To assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon 2-stage design.
Learning about oxytocin: pharmacologic and behavioral issues.
Biological psychiatry, 2014

Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT) plays a role in neuropsychiatric disorders characterized by social dysfunction, the influence of OT on the nonsocial aspects of learning and memory have been less investigated. To foster research in this area, we review the effects of OT on learning and memory in animal models and humans. In healthy animal models, OT improves memory consolidation and extinction, but only if given at a low dose immediately after the acquisition phase. On the contrary, OT effects in healthy humans have been inconsistent; although, in this case, OT was always given before the acquisition phase and no dose-response curves have ever been drawn up. Interestingly, a specific impairment in the reversal of learning has been found in mice devoid of OT receptors and OT has been demonstrated to enhance fear extinction in rodents. All together, these data suggest that OT plays a role in elementary forms of behavioral flexibility and adaptive responses and support its therapeutic potential in neuropsychiatric disorders characterized by cognitive inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease, Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has been shown to improve cognitive flexibility in OT receptor-deficient mice, and scattered findings indicate that intranasal OT has positive effects on the memory of patients with schizophrenia or posttraumatic stress disorders. Further studies of the therapeutic potential of OT as an enhancer of learning and memory are warranted.
Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on the age at onset of neuropsychiatric symptoms in Wilson's disease.
The International journal of neuroscience, 2011

ABSTRACT Wilson's disease (WND) is an autosomal recessive copper storage disease characterized with diverse clinical pictures with the hepatic and/or neuropsychiatric symptoms manifesting at variable age. On the basis of the existing knowledge on possible copper-proinflammatory cytokines interactions, we hypothesized that in WND hereditary, over-/underexpression of PC or anti-inflammatory cytokines may have an impact on the course of the disease. We analyzed the clinical manifestations of WND in relationship to polymorphisms within genes for interleukin-1 receptor antagonist (IL1RN intron 2 VNTR polymorphism), interleukin-1α (IL1A G4845T), IL-1β (IL1B C-511T), IL-6 (IL6 G-174C), and tumor necrosis factor (TNF G-308A) in a total sample of 332 patients. The IL1B C-511T and IL1RN VNTR polymorphisms had an impact on copper metabolism parameters. None of the studied gene polymorphisms had effect on the mode of WND manifestation (neuropsychiatric vs. hepatic). Carriership of the IL1RN *2 allele was related to earlier WND onset, especially among patients with neuropsychiatric form of the disease (median 27.5 vs. 32.0 years, p = .003). Because of the crucial modulatory role of IL1ra on IL-1α and IL-1β proinflammatory functions, IL1ra and its interactions may play a role in the pathogenesis of the neurodegenerative process in WND; our results need to be replicated, possibly in different ethnic groups.
Cognitive Deficits, Changes in Synaptic Function, and Brain Pathology in a Mouse Model of Normal Aging(1,2,3).
eNeuro, 2015

Age is the main risk factor for sporadic Alzheimer's disease. Yet, cognitive decline in aged rodents has been less well studied, possibly due to concomitant changes in sensory or locomotor function that can complicate cognitive tests. We tested mice that were 3, 11, and 23 months old in cognitive, sensory, and motor measures, and postmortem measures of gliosis and neural activity (c-Fos). Hippocampal synaptic function was also examined. While age-related impairments were detectable in tests of spatial memory, greater age-dependent effects were observed in tests of associative learning [active avoidance (AA)]. Gross visual function was largely normal, but startle responses to acoustic stimuli decreased with increased age, possibly due to hearing impairments. Therefore, a novel AA variant in which light alone served as the conditioning stimuli was used. Age-related deficits were again observed. Mild changes in vision, as measured by optokinetic responses, were detected in 19- versus 4-month-old mice, but these were not correlated to AA performance. Thus, deficits in hearing or vision are unlikely to account for the observed deficits in cognitive measures. Increased gliosis was observed in the hippocampal formation at older ages. Age-related changes in neural function and plasticity were observed with decreased c-Fos in the dentate gyrus, and decreased synaptic strength and paired-pulse facilitation in CA1 slices. This work, which carefully outlines age-dependent impairments in cognitive and synaptic function, c-Fos activity, and gliosis during normal aging in the mouse, suggests robust translational measures that will facilitate further study of the biology of aging.
Topical tocopherol for treatment of reticular oral lichen planus: a randomized, double-blind, crossover study.
Oral diseases, 2017

This randomized, double-blind, placebo-controlled crossover study assessed the efficacy of topical tocopherol acetate compared with placebo in easing oral discomfort in patients with reticular oral lichen planus (ROLP).
Impact of medial orbital cortex and medial subthalamic nucleus inactivation, individually and together, on the maintenance of cocaine self-administration behavior in rats.
Behavioural brain research, 2013

A reversible neuronal inactivation procedure was used to study the role of the medial orbital cortex (MO) and medial tip of the subthalamic nucleus (mSTN) in maintenance of cocaine self-administration studied under a second-order schedule of drug and cue presentation. Lidocaine or vehicle was infused 5-min before 1-h self-administration test sessions, using bilateral, asymmetric or unilateral manipulations. The results demonstrated that whether the MO was inactivated bilaterally, unilaterally or asymmetrically (with contralateral mSTN inactivation), cocaine seeking and cocaine intake were reduced. In contrast, bilateral mSTN inactivation did not impact cocaine seeking or cocaine intake, suggesting that the reductions in these measures following asymmetric inactivation may have been due to a unilateral influence of lidocaine in MO. Expression of c-Fos protein was measured in sites downstream of the STN to ensure that the lidocaine inactivation procedure was effective in selectively altering activity of neurons in mSTN. Cocaine-induced c-Fos protein expression was augmented only in the ipsilateral nucleus accumbens core after mSTN lidocaine pretreatment, consistent with the expectation that inactivation of mSTN would disinhibit nucleus accumbens core, but not shell, activity. The present investigation shows the critical importance of the MO for maintaining cocaine seeking and cocaine intake in rats, though its projections to mSTN appear to be unimportant for this purpose. Because cocaine seeking was impacted to such a great extent (45% of baseline, on average), it is likely that MO inactivation exerts its influence on maintenance of cocaine self-administration by interfering primarily with cue-controlled behavior rather than by modifying the reinforcing effects of cocaine.
Changing Clinical and Therapeutic Trends in Tentorial Dural Arteriovenous Fistulas: A Systematic Review.
AJNR. American journal of neuroradiology, 2015

Tentorial dural arteriovenous fistulas are characterized by a high hemorrhagic risk. We evaluated trends in outcomes and management of tentorial dural arteriovenous fistulas and performed a meta-analysis evaluating clinical and angiographic outcomes by treatment technique.
Glutamate-mediated neuroplasticity in an animal model of self-injurious behaviour.
Behavioural brain research, 2008

Self-injurious behaviour (SIB) is exhibited by individuals with a broad variety of developmental disorders and genetic abnormalities, including autism and Lesch-Nyhan, Prader-Willi and Rett syndromes. Most research has focused on environmental factors that reinforce SIB, and less is known about the biological basis of this behaviour disorder. However, animal models have been developed to study the neurochemical pathology that underlies SIB. In one model, rats exhibit self-biting after repeated daily administration of moderately high doses of pemoline (100-200mg/kg). Dopaminergic and glutamatergic neurotransmission have been implicated in this model. Accordingly, we investigated the role of glutamatergic neurotransmission in pemoline-induced SIB, using the N-methyl-d-aspartate (NMDA) receptor antagonists MK-801 and memantine. MK-801 is a high affinity antagonist which blocks glutamate-mediated neuroplasticity and behavioural sensitization to other psychostimulants. It lessened the incidence of SIB, the time spent self-injuring, and the area of tissue damage in the pemoline model. Memantine, on the other hand, is a low affinity antagonist which does not disrupt glutamate-mediated neuroplasticity, and it had little if any effect on any measure of pemoline-induced SIB. These results suggest that repeated pemoline administration induces glutamate-mediated neuroplastic changes that lead to the eventual expression of SIB. Further investigation of these changes may reveal specific neurochemical factors that contribute to SIB in this animal model of self-injury.
Functional organization of envelope-responsive neurons in early visual cortex: organization of carrier tuning properties.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

It is well established that visual cortex neurons having similar selectivity for orientation, direction of motion, ocular dominance, and other properties of first-order (luminance-defined) stimuli are clustered into a columnar organization. However, the cortical architecture of neuronal responses to second-order (contrast/texture-defined) stimuli is poorly understood. A useful second-order stimulus is a contrast envelope, consisting of a finely detailed pattern (carrier) whose contrast varies on a coarse spatial scale (envelope). In this study, we analyzed the cortical organization of carrier tuning properties of neurons, which responded to contrast-modulated stimuli. We examined whether neurons tuned to similar carrier properties are clustered spatially and whether such spatial clusters are arranged in columns. To address these questions, we recorded single-unit activity, multiunit activity, and local field potentials simultaneously from area 18 of anesthetized cats, using single-channel microelectrodes and multielectrode arrays. Our data showed that neurons tuned to similar carrier spatial frequency are distributed in a highly clustered manner; neurons tuned to similar carrier orientation are also significantly clustered. Neurons along linear arrays perpendicular to the brain surface always exhibited similar optimal carrier spatial frequency, indicating a columnar organization. Multi-pronged tetrode recordings indicated that the diameter of these columns is ≥450 μm. Optimal carrier orientation was also significantly clustered but with finer-grain organization and greater scatter. These results indicate a fine anatomical structure of cortical organization of second-order information processing and suggest that there are probably more maps in cat area 18 than previously believed.
Fear bradycardia and activation of the human periaqueductal grey.
NeuroImage, 2013

Animal models of predator defense distinguish qualitatively different behavioral modes that are activated at increasing levels of predation threat. A defense mode observed at intermediate threat levels is freezing: a cessation of locomotion that is characterized by a parasympathetically dominated autonomic nervous system response that causes heart rate deceleration, or fear bradycardia. Studies in rodents have shown that freezing depends on amygdalar projections to the periaqueductal grey (PAG). In humans, freezing-like behaviors are implicated in development and maintenance of psychopathology, but neural mechanisms underlying freezing or its characteristic autonomic response profile have not been identified. Here, we combined event-related blood oxygenation level-dependent functional MRI (BOLD-fMRI) with autonomic response measures in a picture viewing paradigm to probe activity and interconnectivity within the amygdala-PAG pathway and test for an association with parasympathetic as opposed to sympathetic activation. In response to negatively arousing pictures, we observed parasympathetic (bradycardia) and sympathetic (pupil dilation) autonomic responses, BOLD responses in the amygdala and PAG, and effective connectivity between these regions. Critically, BOLD responses in the PAG to negative pictures correlated on a trial-by-trial basis with bradycardia but not pupil dilation. This correlation with bradycardia remained significant when partialling out pupil dilation. Additionally, activity in regions associated with motor planning and inhibition mirrored the PAG response. Thus, our findings implicate the human PAG in a parasympathetically dominated defense mode that subserves a state of attentive immobility. Mechanistic insight into this qualitatively distinct defense mode may importantly advance translational models of anxiety disorders.