rudyvdbrink/CitationDatabase huggingface dataset:
Selective attention in peacocks during assessment of rival males.
The Journal of experimental biology, 2017

Males in many species compete intensely for access to females. In order to minimize costly interactions, they can assess their rivals' competitive abilities by evaluating traits and behaviors. We know little about how males selectively direct their attention to make these assessments. Using Indian peafowl (
Glucocerebrosidase activity, cathepsin D and monomeric α-synuclein interactions in a stem cell derived neuronal model of a PD associated GBA1 mutation.
Neurobiology of disease, 2020

The presence of GBA1 gene mutations increases risk for Parkinson's disease (PD), but the pathogenic mechanisms of GBA1 associated PD remain unknown. Given that impaired α-synuclein turnover is a hallmark of PD pathogenesis and cathepsin D is a key enzyme involved in α-synuclein degradation in neuronal cells, we have examined the relationship of glucocerebrosidase (GCase), cathepsin D and monomeric α-synuclein in human neural crest stem cell derived dopaminergic neurons. We found that normal activity of GCase is necessary for cathepsin D to perform its function of monomeric α-synuclein removal from neurons. GBA1 mutations lead to a lower level of cathepsin D protein and activity, and higher level of monomeric α-synuclein in neurons. When GBA1 mutant neurons were treated with GCase replacement or chaperone therapy; cathepsin D protein levels and activity were restored, and monomeric α-synuclein decreased. When cathepsin D was inhibited, GCase replacement failed to reduce monomeric α-synuclein levels in GBA1 mutant neurons. These data indicate that GBA1 gene mutations increase monomeric α-synuclein levels via an effect on lysosomal cathepsin D in neurons.
The lateral hypothalamic area controls paradoxical (REM) sleep by means of descending projections to brainstem GABAergic neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

It has recently been shown that the ventrolateral part of the periaqueductal gray (VLPAG) and the adjacent dorsal deep mesencephalic nucleus (dDpMe) contain GABAergic neurons gating paradoxical sleep (PS) onset by means of their projection to the glutamatergic PS-on neurons of the sublaterodorsal tegmental nucleus (SLD). To determine the mechanisms responsible for the cessation of activity of these GABAergic PS-off neurons at the onset and during PS, we combined the immunostaining of c-FOS, a marker of neuronal activation, with cholera toxin b subunit (CTb) retrograde tracing from the VLPAG/dDpMe in three groups of rats (control, PS deprived, and PS hypersomniac). We found that the lateral hypothalamic area (LH) is the only brain structure containing a very large number of neurons activated during PS hypersomnia and projecting to the VLPAG/dDpMe. We further demonstrated that 44% of these neurons express the neuropeptide melanin concentrating hormone (MCH). We then showed that bilateral injections in the LH of two inhibitory compounds, clonidine (an α-2 adrenergic agonist) and muscimol (a GABAa agonist) induce an inhibition of PS. Furthermore, after muscimol injections in the LH, the VLPAG/dDpMe contained a large number of activated neurons, mostly GABAergic, and projecting to the SLD. Altogether, our results indicate for the first time that the activation of a population of LH neurons, in part MCH containing, is necessary for PS to occur. Furthermore, our results strongly suggest that these neurons trigger PS by means of their inhibitory projection to the PS-off GABAergic neurons located in the VLPAG/dDpMe.
Hypothalamic control of male aggression-seeking behavior.
Nature neuroscience, 2016

In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to gain brief and repeated access to a weaker male that they could attack. In males that exhibited rapid task learning, we found that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, was essential for aggression-seeking. Using both single-unit electrophysiology and population optical recording, we found that VMHvl neurons became active during aggression-seeking and that their activity tracked changes in task learning and extinction. Inactivation of the VMHvl reduced aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerated moment-to-moment aggression-seeking and intensified future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.
Influence of DARPP-32 genetic variation on BOLD activation to happy faces.
Social cognitive and affective neuroscience, 2017

Dopaminergic pathways play a crucial role in reward processing, and advanced age can modulate its efficiency. DARPP-32 controls dopaminergic function and is a chemical nexus of reward processing. In 61 younger (20-30 years) and older adults (54% ♀) (65-74 years), we examined how blood-oxygen-level dependent (BOLD) activation to emotional faces, vary over genotypes at three single nucleotide polymorphism (SNPs), coding for DARPP-32 (rs879606; rs907094; 3764352). We also assessed age-magnification of DARPP-32 effects on BOLD activation. We found that major homozygote G, T or A genotypes, with higher cortical expression of DARPP-32, higher dopamine receptor efficacy, and greater bias toward positive cues, had increased functional connectivity in cortical-subcortical circuits in response to happy faces, engaging the dorsal prefrontal cortex (DLPFC), fusiform gyrus (FG) and the midbrain (MB). Local BOLD response to happy faces in FG, and MB was age-dependent, so that older carriers of the major G, T or A alleles showed lesser activation than minor genotypes. These genetic variants of DARPP-32 did not modulate BOLD response to angry faces, or engagement of the inferior occipital gyrus, to happy or angry faces. Taken together our results lend support for a potential role of DARPP-32 genetic variants in neural response to potential reward triggering cues.
Inhibitory descending rhombencephalic projections in larval sea lamprey.
Neuroscience, 2011

Lampreys are jawless vertebrates, the most basal group of extant vertebrates. This phylogenetic position makes them invaluable models in comparative studies of the vertebrate central nervous system. Lampreys have been used as vertebrate models to study the neuronal circuits underlying locomotion control and axonal regeneration after spinal cord injury. Inhibitory inputs are key elements in the networks controlling locomotor behaviour, but very little is known about the descending inhibitory projections in lampreys. The aim of this study was to investigate the presence of brain-spinal descending inhibitory pathways in larval stages of the sea lamprey Petromyzon marinus by means of tract-tracing with neurobiotin, combined with immunofluorescence triple-labeling methods. Neurobiotin was applied in the rostral spinal cord at the level of the third gill, and inhibitory populations were identified by the use of cocktails of antibodies raised against glycine and GABA. Glycine-immunoreactive (-ir) neurons that project to the spinal cord were observed in three rhombencephalic reticular nuclei: anterior, middle and posterior. Spinal-projecting GABA-ir neurons were observed in the anterior and posterior reticular nuclei. Double glycine-ir/GABA-ir spinal cord-projecting neurons were only observed in the posterior reticular nucleus, and most glycine-ir neurons did not display GABA immunoreactivity. The present results reveal the existence of inhibitory descending projections from brainstem reticular neurons to the spinal cord, which were analyzed in comparative and functional contexts. Further studies should investigate which spinal cord circuits are affected by these descending inhibitory projections.
Frontotemporal dementia as a frontostriatal disorder: neostriatal morphology as a biomarker and structural basis for an endophenotype.
The Australian and New Zealand journal of psychiatry, 2012

This article reviews the evidence for a re-conceptualisation of a subtype of frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), as a frontostriatal disorder, working towards an endophenotype.
An effect of posture on anticipatory anxiety.
The International journal of neuroscience, 2008

This study investigated the effects of body posture on state anxiety and psychological stress. Twenty normal adults performed a demanding mental arithmetic task in both standing and supine conditions, with subjective measures of anxiety and stress obtained before, immediately, and 10 min after the task. Participants were found to experience anticipatory anxiety when standing, although not when supine. The mechanism underlying this effect remains to be determined, although it could involve a postural difference in baroreceptor load.
Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease.
Neurobiology of aging, 2012

Huntington's disease (HD) is associated with profound autonomic dysfunction including dysregulation of cardiovascular control often preceding cognitive or motor symptoms. Brain-derived neurotrophic factor (BDNF) levels are decreased in the brains of HD patients and HD mouse models, and restoring BDNF levels prevents neuronal loss and extends survival in HD mice. We reasoned that heart rate changes in HD may be associated with altered BDNF signaling in cardiovascular control nuclei in the brainstem. Here we show that heart rate is elevated in HD (N171-82Q) mice at presymptomatic and early disease stages, and heart rate responses to restraint stress are attenuated. BDNF levels were significantly reduced in brainstem regions containing cardiovascular nuclei in HD mice and human HD patients. Central administration of BDNF restored the heart rate to control levels. Our findings establish a link between diminished BDNF expression in brainstem cardiovascular nuclei and abnormal heart rates in HD mice, and suggest a novel therapeutic target for correcting cardiovascular dysfunction in HD.
Synapsin I Synchronizes GABA Release in Distinct Interneuron Subpopulations.
Cerebral cortex (New York, N.Y. : 1991), 2020

Neurotransmitters can be released either synchronously or asynchronously with respect to action potential timing. Synapsins (Syns) are a family of synaptic vesicle (SV) phosphoproteins that assist gamma-aminobutyric acid (GABA) release and allow a physiological excitation/inhibition balance. Consistently, deletion of either or both Syn1 and Syn2 genes is epileptogenic. In this work, we have characterized the effect of SynI knockout (KO) in the regulation of GABA release dynamics. Using patch-clamp recordings in hippocampal slices, we demonstrate that the lack of SynI impairs synchronous GABA release via a reduction of the readily releasable SVs and, in parallel, increases asynchronous GABA release. The effects of SynI deletion on synchronous GABA release were occluded by ω-AgatoxinIVA, indicating the involvement of P/Q-type Ca2+channel-expressing neurons. Using in situ hybridization, we show that SynI is more expressed in parvalbumin (PV) interneurons, characterized by synchronous release, than in cholecystokinin or SOM interneurons, characterized by a more asynchronous release. Optogenetic activation of PV and SOM interneurons revealed a specific reduction of synchronous release in PV/SynIKO interneurons associated with an increased asynchronous release in SOM/SynIKO interneurons. The results demonstrate that SynI is differentially expressed in interneuron subpopulations, where it boosts synchronous and limits asynchronous GABA release.
Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity.
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2019

The amyloid-β (Aβ) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers-and their membrane-perturbing effects-can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic Aβ oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between Aβ oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients.
Neurobiological systems in dyslexia.
Trends in neuroscience and education, 2019

Biological systems-level principles of the genetic landscape underlying the neurobiology of dyslexia provide a novel and heuristic theoretical framework for a new understanding of the disability. Dyslexia may result from reduced neuroplasticity and earlier peak of maturation of the posterior corpus callosum, temporoparietal region of the left hemisphere reading network, and temporoparietal region of the right hemisphere circuitry of attentional networks. This precocious abridgement of a typically prolonged maturation originates prenatally or in early childhood, driven by environmentally-guided epigenetic mechanisms as retrogressive, adaptive responses to stress. Epigenetics suggests the importance of identifying circumstances that influence reading-related maturational timing; and network control theory suggests an instructional orientation for enhancing plasticity. Thus, dyslexia may be an unexceptional genetic variation resulting from gene/environment interactions.
Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls.
iScience, 2020

Amyotrophic lateral sclerosis (ALS) is a disorder with immune alterations that augment disease severity. M2 macrophages benefit diabetic and nephrotic mice by suppressing the pro-inflammatory state. However, neither have M2 cells been investigated in ALS nor have human induced pluripotent stem cell (iPSC)-derived M2 cells been thoroughly studied for immunosuppressive potentials. Here, iPSCs of C9orf72 mutated or sporadic ALS patients were differentiated into M2 macrophages, which suppressed activation of pro-inflammatory M1 macrophages as well as proliferation of ALS CD4
Multiple genetic variations confer risks for obesity and type 2 diabetes mellitus in arab descendants from UAE.
International journal of obesity (2005), 2018

The United Arab Emirates (UAE) is one of the countries most threatened with obesity. Here we investigated associations between hundreds of single-nucleotide polymorphisms (SNPs) and the following obesity indicators: body mass index (BMI), waist circumference (WC), and height. We also investigated the associations between obesity-related genes with type 2 diabetes mellitus (T2DM).
The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice.
Disease models & mechanisms, 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system. ALS etiology is highly multifactorial and multifarious, and an effective treatment is still lacking. Neuroinflammation is a hallmark of ALS and could be targeted to develop new therapeutic approaches. Interestingly, the transcription factor Nurr1 has been demonstrated to have an important role in the inflammatory process in several neurological disorders, such as Parkinson's disease and multiple sclerosis. In the present paper, we demonstrate for the first time that Nurr1 expression levels are upregulated in the peripheral blood of ALS patients. Moreover, we investigated Nurr1 function in the SOD1-G93A mouse model of ALS. Nurr1 was strongly upregulated in the spinal cord during the asymptomatic and early symptomatic phases of the disease, where it promoted the expression of brain-derived neurotrophic factor mRNA and the repression of NFκB pro-inflammatory targets, such as inducible nitric oxide synthase. Therefore, we hypothesize that Nurr1 is activated in an early phase of the disease as a protective endogenous anti-inflammatory mechanism, although not sufficient to reverse disease progression. On the basis of these observations, Nurr1 could represent a potential biomarker for ALS and a promising target for future therapies.
"Cuts in Action": A High-Density EEG Study Investigating the Neural Correlates of Different Editing Techniques in Film.
Cognitive science, 2017

In spite of their striking differences with real-life perception, films are perceived and understood without effort. Cognitive film theory attributes this to the system of continuity editing, a system of editing guidelines outlining the effect of different cuts and edits on spectators. A major principle in this framework is the 180° rule, a rule recommendation that, to avoid spectators' attention to the editing, two edited shots of the same event or action should not be filmed from angles differing in a way that expectations of spatial continuity are strongly violated. In the present study, we used high-density EEG to explore the neural underpinnings of this rule. In particular, our analysis shows that cuts and edits in general elicit early ERP component indicating the registration of syntactic violations as known from language, music, and action processing. However, continuity edits and cuts-across the line differ from each other regarding later components likely to be indicating the differences in spatial remapping as well as in the degree of conscious awareness of one's own perception. Interestingly, a time-frequency analysis of the occipital alpha rhythm did not support the hypothesis that such differences in processing routes are mainly linked to visual attention. On the contrary, our study found specific modulations of the central mu rhythm ERD as an indicator of sensorimotor activity, suggesting that sensorimotor networks might play an important role. We think that these findings shed new light on current discussions about the role of attention and embodied perception in film perception and should be considered when explaining spectators' different experience of different kinds of cuts.
The control of release probability at nerve terminals.
Nature reviews. Neuroscience, 2019

Exocytosis is a fundamental membrane fusion process by which the soluble or membrane-associated cargoes of a secretory vesicle are delivered to the extracellular milieu or the cell surface. While essential for all organs, the brain relies on a specialized form of exocytosis to mediate information flow throughout its vast circuitry. Neurotransmitter-laden synaptic vesicles fuse with the plasma membrane on cue with astonishing speed in a probabilistic process that is both tightly regulated and capable of a fascinating array of plasticities. Here, we examine progress in the molecular understanding of synaptic vesicle fusion and its control.
Optogenetically induced low-frequency correlations impair perception.
eLife, 2019

Deployment of covert attention to a spatial location can cause large decreases in low-frequency correlated variability among neurons in macaque area V4 whose receptive-fields lie at the attended location. It has been estimated that this reduction accounts for a substantial fraction of the attention-mediated improvement in sensory processing. These estimates depend on assumptions about how population signals are decoded and the conclusion that correlated variability impairs perception, is purely hypothetical. Here we test this proposal directly by optogenetically inducing low-frequency fluctuations, to see if this interferes with performance in an attention-demanding task. We find that low-frequency optical stimulation of neurons in V4 elevates correlations among pairs of neurons and impairs the animal's ability to make fine sensory discriminations. Stimulation at higher frequencies does not impair performance, despite comparable modulation of neuronal responses. These results support the hypothesis that attention-dependent reductions in correlated variability contribute to improved perception of attended stimuli.
Connectivity and ultrastructure of dopaminergic innervation of the inner ear and auditory efferent system of a vocal fish.
The Journal of comparative neurology, 2017

Dopamine (DA) is a conserved modulator of vertebrate neural circuitry, yet our knowledge of its role in peripheral auditory processing is limited to mammals. The present study combines immunohistochemistry, neural tract tracing, and electron microscopy to investigate the origin and synaptic characteristics of DA fibers innervating the inner ear and the hindbrain auditory efferent nucleus in the plainfin midshipman, a vocal fish that relies upon the detection of mate calls for reproductive success. We identify a DA cell group in the diencephalon as a common source for innervation of both the hindbrain auditory efferent nucleus and saccule, the main hearing endorgan of the inner ear. We show that DA terminals in the saccule contain vesicles but transmitter release appears paracrine in nature, due to the apparent lack of synaptic contacts. In contrast, in the hindbrain, DA terminals form traditional synaptic contacts with auditory efferent neuronal cell bodies and dendrites, as well as unlabeled axon terminals, which, in turn, form inhibitory-like synapses on auditory efferent somata. Our results suggest a distinct functional role for brain-derived DA in the direct and indirect modulation of the peripheral auditory system of a vocal nonmammalian vertebrate.