rudyvdbrink/CitationDatabase huggingface dataset:
Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble.
Nature neuroscience, 2020

The epigenome and three-dimensional (3D) genomic architecture are emerging as key factors in the dynamic regulation of different transcriptional programs required for neuronal functions. In this study, we used an activity-dependent tagging system in mice to determine the epigenetic state, 3D genome architecture and transcriptional landscape of engram cells over the lifespan of memory formation and recall. Our findings reveal that memory encoding leads to an epigenetic priming event, marked by increased accessibility of enhancers without the corresponding transcriptional changes. Memory consolidation subsequently results in spatial reorganization of large chromatin segments and promoter-enhancer interactions. Finally, with reactivation, engram neurons use a subset of de novo long-range interactions, where primed enhancers are brought in contact with their respective promoters to upregulate genes involved in local protein translation in synaptic compartments. Collectively, our work elucidates the comprehensive transcriptional and epigenomic landscape across the lifespan of memory formation and recall in the hippocampal engram ensemble.
Association between high-sensitivity C-reactive protein levels and clinical outcomes in acute ischemic stroke patients treated with endovascular therapy.
Annals of translational medicine, 2020

Increasing evidence demonstrates that high-sensitivity C-reactive protein (hs-CRP) is an independent prognostic predictor in acute ischemic stroke (AIS) patients. The purpose of this study is to investigate the association between hs-CRP levels and clinical outcomes in AIS patients receiving endovascular therapy (EVT).
Serotonin distribution in the brain of the plainfin midshipman: Substrates for vocal-acoustic modulation and a reevaluation of the serotonergic system in teleost fishes.
The Journal of comparative neurology, 2020

Serotonin (5-HT) is a modulator of neural circuitry underlying motor patterning, homeostatic control, and social behavior. While previous studies have described 5-HT distribution in various teleosts, serotonergic raphe subgroups in fish are not well defined and therefore remain problematic for cross-species comparisons. Here we used the plainfin midshipman fish, Porichthys notatus, a well-studied model for investigating the neural and hormonal mechanisms of vertebrate vocal-acoustic communication, to redefine raphe subgroups based on both stringent neuroanatomical landmarks as well as quantitative cell measurements. In addition, we comprehensively characterized 5-HT-immunoreactive (-ir) innervation throughout the brain, including well-delineated vocal and auditory nuclei. We report neuroanatomical heterogeneity in populations of the serotonergic raphe nuclei of the brainstem reticular formation, with three discrete subregions in the superior raphe, an intermediate 5-HT-ir cell cluster, and an extensive inferior raphe population. 5-HT-ir neurons were also observed within the vocal motor nucleus (VMN), forming putative contacts on those cells. In addition, three major 5-HT-ir cell groups were identified in the hypothalamus and one group in the pretectum. Significant 5-HT-ir innervation was found in components of the vocal pattern generator and cranial motor nuclei. All vocal midbrain nuclei showed considerable 5-HT-ir innervation, as did thalamic and hindbrain auditory and lateral line areas and vocal-acoustic integration sites in the preoptic area and ventral telencephalon. This comprehensive atlas offers new insights into the organization of 5-HT nuclei in teleosts and provides neuroanatomical evidence for serotonin as a modulator of vocal-acoustic circuitry and behavior in midshipman fish, consistent with findings in vocal tetrapods.
Lercanidipine and T-type calcium current.
European review for medical and pharmacological sciences, 2018

Lercanidipine is a calcium antagonist with no cardiodepressant activity, long lasting antihypertensive action and reno-protective effect. Our previous data demonstrated that lercanidipine blocks L-type calcium channels (CaL). However, no data are available concerning its effects on T-type calcium channels (CaT). The aim of this study was to evaluate the effect on both CaL and CaT and the selectivity ratio of R-lercanidipine, S-lercanidipine and RS-lercanidipine. A comparison with other dihydropyridines (amlodipine and lacidipine) and the CaT blocker mibefradil was also performed.
Fronto-striatal circuits for cognitive flexibility in far from onset Huntington's disease: evidence from the Young Adult Study.
Journal of neurology, neurosurgery, and psychiatry, 2021

Cognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and is impaired in both manifest and premanifest Huntington's disease (pre-HD). The aim of this study was to examine cognitive flexibility in a far from onset pre-HD cohort to determine whether an early impairment exists and if so, whether fronto-striatal circuits were associated with this deficit.
The attentional boost effect enhances the recognition of bound features in short-term memory.
Memory (Hove, England), 2020

In the Attentional Boost Effect (ABE), images or words encoded with unrelated to-be-responded targets are later remembered better than images or words encoded with to-be-ignored distractors. In the realm of short-term memory, the ABE has been previously shown to enhance the short-term recognition of single-feature stimuli. The present study replicated this finding and extended it to a condition requiring the encoding and retention of colour-shape associations. Across four experiments, participants studied arrays of four coloured squares (the colour-only condition), four gray shapes (the shape-only condition) or four coloured shapes (the binding condition), paired with either a target letter (to which participants had to respond by pressing the spacebar) or a distractor letter (for which no response was required). After a short delay, they were presented with a probe array and asked to decide whether it matched or not the encoded array. Results showed that, in all conditions, the recognition of target-paired arrays was significantly better than the recognition of distractor-paired arrays. These findings suggest that the ABE can enhance feature binding.
Role of autobiographical memory in the impact of MBCT on dysfunctional attitudes, depressive symptoms and anxiety in bipolar I patients.
Journal of affective disorders, 2020

The literature suggests that cognitive reactivity in bipolar patients can increase relapse vulnerability, is enhanced by depressive mood and dysfunctional attitudes, and could be improved with MBCT. Autobiographical memory (AM) could be involved in cognitive reactivity, and improved with MBCT training. This study aims to investigate the effect of MBCT for bipolar patients on depressive and anxious symptoms, dysfunctional attitudes and AM, and the predictive versus mediating role of AM in the impact of MBCT on clinical symptoms.
Linguistic profiles, brain metabolic patterns and rates of amyloid-β biomarker positivity in patients with mixed primary progressive aphasia.
Neurobiology of aging, 2020

We aimed to detail language profiles, brain metabolic patterns and proportion of Alzheimer's disease biomarkers in a cohort of patients with mixed primary progressive aphasia (mPPA). We considered 58 patients with PPA: 10 with non-fluent/agrammatic variant (nfvPPA), 16 with semantic variant (svPPA), 21 with logopenic variant (lvPPA) and 9 with mPPA. Patients with mPPA were further classified as 4 nf/lvPPA (with prevailing features for nfvPPA and lvPPA) and 5 s/lvPPA (with prevailing features for svPPA and lvPPA). Nf/lvPPA patients were characterized by higher proportion of Naming impairment compared to nfvPPA and more frequent Grammatical Errors and Phonologic Errors than lvPPA. S/lvPPA had higher proportion of impairment in Sentences Repetition compared to svPPA and in Single-word Comprehension compared to lvPPA. 100% of nf/lvPPA and 40% of s/lvPPA had Aβ positive biomarkers. Brain hypometabolic pattern in Nf/lvPPA was consistent with lvPPA, while s/lvPPA had a brain metabolism resembling svPPA. We concluded that nf/lvPPA patients might be considered as PPA variant due to Alzheimer's disease and s/lvPPA group mainly included patients with svPPA.
A sapphire based monolithic integrated optrode.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2016

A novel kind of optrode fabricated on a sapphire substrate is proposed for optogenetic applications in neuroscience. Eight thin-film neural electrodes and a GaN-LED are monolithically integrated on the surface of a sapphire shank. The LED is used for optogenetic stimulation and the multiple electrodes are used for simultaneous recording of neural activities. The output power density of the LED is 1-19 mW/mm2 at 468 nm, driving with a current from 0.7-10 mA. The mean electrochemical impedance of the eight recoding sites on the optrode at 1 kHz is 385 kΩ. The highest temperature-raise at tissue around the LED is almost 1 °C when the output power density is 3 mw/mm2. The monolithic integrated structure will make it a powerful tool for optogenetics.
A Disinhibitory Circuit for Contextual Modulation in Primary Visual Cortex.
Neuron, 2020

Context guides perception by influencing stimulus saliency. Accordingly, in visual cortex, responses to a stimulus are modulated by context, the visual scene surrounding the stimulus. Responses are suppressed when stimulus and surround are similar but not when they differ. The underlying mechanisms remain unclear. Here, we use optical recordings, manipulations, and computational modeling to show that disinhibitory circuits consisting of vasoactive intestinal peptide (VIP)-expressing and somatostatin (SOM)-expressing inhibitory neurons modulate responses in mouse visual cortex depending on similarity between stimulus and surround, primarily by modulating recurrent excitation. When stimulus and surround are similar, VIP neurons are inactive, and activity of SOM neurons leads to suppression of excitatory neurons. However, when stimulus and surround differ, VIP neurons are active, inhibiting SOM neurons, which leads to relief of excitatory neurons from suppression. We have identified a canonical cortical disinhibitory circuit that contributes to contextual modulation and may regulate perceptual saliency.
Networking of glucagon-like peptide-1 axons with GnRH neurons in the basal forebrain of male mice revealed by 3DISCO-based immunocytochemistry and optogenetics.
Brain structure & function, 2021

Glucagon-like peptide-1 (GLP-1) regulates reproduction centrally, although, the neuroanatomical basis of the process is unknown. Therefore, the putative networking of the central GLP-1 and gonadotropin-releasing hormone (GnRH) systems was addressed in male mice using whole mount immunocytochemistry and optogenetics. Enhanced antibody penetration and optical clearing procedures applied to 500-1000 µm thick basal forebrain slices allowed the simultaneous visualization of the two distinct systems in the basal forebrain. Beaded GLP-1-IR axons innervated about a quarter of GnRH neurons (23.2 ± 1.4%) forming either single or multiple contacts. GnRH dendrites received a more intense GLP-1 innervation (64.6 ± 0.03%) than perikarya (35.4 ± 0.03%). The physiological significance of the innervation was examined by optogenetic activation of channelrhodopsin-2 (ChR2)-expressing axons of preproglucagon (GCG) neurons upon the firing of GnRH neurons by patch clamp electrophysiology in acute brain slices of triple transgenic mice (Gcg-cre/ChR2/GFP-GnRH). High-frequency laser beam stimulation (20 Hz, 10 ms pulse width, 3 mW laser power) of ChR2-expressing GCG axons in the mPOA increased the firing rate of GnRH neurons (by 75 ± 17.3%, p = 0.0007). Application of the GLP-1 receptor antagonist, Exendin-3-(9-39) (1 μM), prior to the photo-stimulation, abolished the facilitatory effect. In contrast, low-frequency trains of laser pulses (0.2 Hz, 60 pulses) had no effect on the spontaneous postsynaptic currents of GnRH neurons. The findings indicate a direct wiring of GLP-1 neurons with GnRH cells which route is excitatory for the GnRH system. The pathway may relay metabolic signals to GnRH neurons and synchronize metabolism with reproduction.
Trisk 95 as a novel skin mirror for normal and diabetic systemic glucose level.
Scientific reports, 2020

Developing trustworthy, cost effective, minimally or non-invasive glucose sensing strategies is of great need for diabetic patients. In this study, we used an experimental type I diabetic mouse model to examine whether the skin would provide novel means for identifying biomarkers associated with blood glucose level. We first showed that skin glucose levels are rapidly influenced by blood glucose concentrations. We then conducted a proteomic screen of murine skin using an experimental in vivo model of type I diabetes and wild-type controls. Among the proteins that increased expression in response to high blood glucose, Trisk 95 expression was significantly induced independently of insulin signalling. A luciferase reporter assay demonstrated that the induction of Trisk 95 expression occurs at a transcriptional level and is associated with a marked elevation in the Fluo-4AM signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. Moreover, Trisk 95 knockout abolishes both the calcium flux and the mitochondrial phenotype changes indicating dependency of glucose flux in the skin on Trisk 95 function. The data demonstrate that the skin reacts robustly to systemic blood changes, and that Trisk 95 is a promising biomarker for a glucose monitoring assembly.
Primary motor cortex excitability as a marker of plasticity in a stimulation protocol combining action observation and kinesthetic illusion of movement.
The European journal of neuroscience, 2021

Action observation combined with proprioceptive stimulation able to induce a kinesthetic illusion of movement (AO-KI) was shown to elicit a plastic increase in primary motor cortex (M1) excitability, with promising applications in rehabilitative interventions. Nevertheless, the known individual variability in response to combined stimulation protocols limits its application. The aim of this study was to examine whether a relationship exists between changes in M1 excitability during AO-KI and the long-lasting changes in M1 induced by AO-KI. Fifteen volunteers received a conditioning protocol consisting in watching a video showing a thumb-opposition movement and a simultaneous proprioceptive stimulation that evoked an illusory kinesthetic experience of their thumbs closing. M1 excitability was evaluated by means of single-pulse transcranial magnetic stimulation before, DURING the conditioning protocol, and up to 60 min AFTER it was administered. M1 excitability significantly increased during AO-KI with respect to a rest condition. Furthermore, AO-KI induced a long-lasting increase in M1 excitability up to 60 min after administration. Finally, a significant positive correlation appeared between M1 excitability changes during and after AO-KI; that is, participants who were more responsive during AO-KI showed greater motor cortical activity changes after it. These findings suggest that M1 response during AO-KI can be considered a neurophysiological marker of individual responsiveness to the combined stimulation since it was predictive of its efficacy in inducing long-lasting M1 increase excitability. This information would allow knowing in advance whether an individual will be a responder to AO-KI.
Visualization of the Superior Ocular Sulcus during Danio rerio Embryogenesis.
Journal of visualized experiments : JoVE, 2019

Congenital ocular coloboma is a genetic disorder that is typically observed as a cleft in the inferior aspect of the eye resulting from incomplete choroid fissure closure. Recently, the identification of individuals with coloboma in the superior aspect of the iris, retina, and lens led to the discovery of a novel structure, referred to as the superior fissure or superior ocular sulcus (SOS), that is transiently present on the dorsal aspect of the optic cup during vertebrate eye development. Although this structure is conserved across mice, chick, fish, and newt, our current understanding of the SOS is limited. In order to elucidate factors that contribute to its formation and closure, it is imperative to be able to observe it and identify abnormalities, such as delay in the closure of the SOS. Here, we set out to create a standardized series of protocols that can be used to efficiently visualize the SOS by combining widely available microscopy techniques with common molecular biology techniques such as immunofluorescent staining and mRNA overexpression. While this set of protocols focuses on the ability to observe SOS closure delay, it is adaptable to the experimenter's needs and can be easily modified. Overall, we hope to create an approachable method through which our understanding of the SOS can be advanced to expand the current knowledge of vertebrate eye development.
Molecularly Defined Hippocampal Inputs Regulate Population Dynamics in the Prelimbic Cortex to Suppress Context Fear Memory Retrieval.
Biological psychiatry, 2020

Context fear memory dysregulation is a hallmark symptom of several neuropsychiatric disorders, including generalized anxiety disorder and posttraumatic stress disorder. The hippocampus (HC) and prelimbic (PrL) subregion of the medial prefrontal cortex have been linked with context fear memory retrieval in rodents, but the mechanisms by which HC-PrL circuitry regulates this process remain poorly understood.
The Neuroanatomy of Reproduction: Seeing Is Believing.
Seminars in reproductive medicine, 2019

The brain is the central controller of reproduction and the menstrual cycle. Reproductive endocrinologists spend their days treating patients with perturbations in reproduction as a result of pituitary diseases and manipulate pituitary hormones to enhance fertility and quality of life. Microscopic neuroanatomical images will allow a better understanding of how a tumor in the pituitary might affect vision, or a mass in the brain might cause amenorrhea. Clinical correlations that are taught every day become much clearer once the anatomical relationships are explored. The objective of this pictorial tour is to elucidate anatomical and clinical relationships while showcasing the neuroanatomy of reproduction.
Exercise Addiction Prevalence and Correlates in the Absence of Eating Disorder Symptomology: A Systematic Review and Meta-analysis.
Journal of addiction medicine, 2020

Exercise addiction (EA) can be debilitating and can be a symptom of an eating disorder. To date, the prevalence rates of EA without indicated eating disorders in the general population and associated correlates remain unreported.
Multi-view 3D skin feature recognition and localization for patient tracking in spinal surgery applications.
Biomedical engineering online, 2021

Minimally invasive spine surgery is dependent on accurate navigation. Computer-assisted navigation is increasingly used in minimally invasive surgery (MIS), but current solutions require the use of reference markers in the surgical field for both patient and instruments tracking.
Genome-wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2017

Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10
Hypocretins and primary headaches: neurobiology and clinical implications.
Expert review of neurotherapeutics, 2008

Hypocretins (or orexins) are two neuropeptides synthesized by neurons located exclusively in the hypothalamus. Hypocretin-containing neurons have widespread projections throughout the CNS; with particularly dense excitatory projections to monoaminergic and serotonergic brainstem centers. The hypocretin system influences a wide range of physiological processes in mammals, such as feeding, arousal, rewards and drug addiction. Recently, a number of studies in experimental animals showed that hypocretins are involved in pain modulation within the CNS, and suggested the presence of a link between these peptides and nociceptive phenomena observed in primary headaches. The aim of this review is to describe and discuss recent studies in humans suggesting a role for the hypocretin neuronal system in cluster headache and chronic migraine.
Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery.
Neuroscience, 2021

Vestibular nerve afferents are divided into regular and irregular groups based on the variability of interspike intervals in their resting discharge. Most afferents receive inputs from bouton terminals that contact type II hair cells as well as from calyx terminals that cover the basolateral walls of type I hair cells. Calyces have an abundance of different subtypes of KCNQ (Kv7) potassium channels and muscarinic acetylcholine receptors (mAChRs) and receive cholinergic efferent inputs from neurons in the brainstem. We investigated whether mAChRs affected membrane properties and firing patterns of calyx terminals through modulation of KCNQ channel activity. Patch clamp recordings were performed from calyx terminals in central regions of the cristae of the horizontal and anterior canals in 13-26 day old Sprague-Dawley rats. KCNQ mediated currents were observed as voltage sensitive currents with slow kinetics (activation and deactivation), resulting in spike frequency adaptation so that calyces at best fired a single action potential at the beginning of a depolarizing step. Activation of mAChRs by application of oxotremorine methiodide or inhibition of KCNQ channels by linopirdine dihydrochloride decreased voltage activated currents by ∼30%, decreased first spike latencies by ∼40%, resulted in action potential generation in response to smaller current injections and at lower (i.e., more hyperpolarized) membrane potentials, and increased the number of spikes fired during depolarizing steps. Interestingly, some of the calyces showed spontaneous discharge in the presence of these drugs. Together, these findings suggest that cholinergic efferents can modulate the response properties and encoding of head movements by afferents.