rudyvdbrink/CitationDatabase huggingface dataset:
Sleep disorders in Parkinsonian macaques: effects of L-dopa treatment and pedunculopontine nucleus lesion.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Patients with Parkinson's disease (PD) display significant sleep disturbances and daytime sleepiness. Dopaminergic treatment dramatically improves PD motor symptoms, but its action on sleep remains controversial, suggesting a causal role of nondopaminergic lesions in these symptoms. Because the pedunculopontine nucleus (PPN) regulates sleep and arousal, and in view of the loss of its cholinergic neurons in PD, the PPN could be involved in these sleep disorders. The aims of this study were as follows: (1) to characterize sleep disorders in a monkey model of PD; (2) to investigate whether l-dopa treatment alleviates sleep disorders; and (3) to determine whether a cholinergic PPN lesion would add specific sleep alterations. To this end, long-term continuous electroencephalographic monitoring of vigilance states was performed in macaques, using an implanted miniaturized telemetry device. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment induced sleep disorders that comprised sleep episodes during daytime and sleep fragmentation and a reduction of sleep efficiency at nighttime. It also induced a reduction in time spent in rapid eye movement (REM) sleep and slow-wave sleep and an increase in muscle tone during REM and non-REM sleep episodes and in the number of awakenings and movements. l-Dopa treatment resulted in a partial but significant improvement of almost all sleep parameters. PPN lesion induced a transient decrease in REM sleep and in slow-wave sleep followed by a slight improvement of sleep quality. Our data demonstrate the efficacy of l-dopa treatment in improving sleep disorders in parkinsonian monkeys, and that adding a cholinergic PPN lesion improves sleep quality after transient sleep impairment.
Activation of the medial prefrontal cortex by escapable stress is necessary for protection against subsequent inescapable stress-induced potentiation of morphine conditioned place preference.
The European journal of neuroscience, 2012

Stress can be a predisposing factor in the development of psychiatric disorders. However, not all individuals develop psychiatric disorders following a traumatic event. An attempt to understand these individual differences has led to a focus on factors that produce resistance. Interestingly, in rats, an experience with escapable tailshock (ES) before inescapable tailshock (IS) prevents the typical anxiety-like behavioral outcomes of IS. This type of resistance has been termed 'behavioral immunization', and it depends on activation of the medial prefrontal cortex (mPFC) during ES. However, one outcome of IS that is not anxiety-related is potentiation of morphine conditioned place preference (CPP). The present experiments investigated whether prior ES would block IS-induced potentiation of morphine CPP. Rats received either ES, IS or homecage control treatment on day 1 and then either IS or homecage control treatment on day 2. Twenty-four hours following day 2, rats underwent morphine conditioning, and CPP was subsequently assessed. In a second experiment, rats received ES 3, 14 or 56 days prior to IS to determine the duration of behavioral immunization. In a final experiment, rats were microinjected with the GABA(A) agonist muscimol (50 ng/0.5 μL) or saline in the mPFC before day 1 of stress. Prior ES blocked IS-induced potentiation of morphine CPP. This immunizing effect of ES lasted for at least 56 days. Additionally, intra-mPFC muscimol during ES prevented behavioral immunization. These results suggest that prior experience with ES activates the mPFC and produces long-lasting neural alterations that block subsequent IS-induced potentiation of morphine CPP.
Optimized protocol for conditioned place avoidance learning in juvenile zebrafish.
STAR protocols, 2021

Conditioned place avoidance assays are broadly used in mammals to study different cognitive aspects of operant learning. Here, we introduce a series of experimental designs for training juvenile zebrafish in short-term and long-term conditioned place avoidance assays. Our goal is to promote standardization of animal handling procedures and setup conditions to improve animal welfare and reproducibility while studying operant learning behaviors in juvenile zebrafish. For complete details on the use and execution of this protocol, please refer to Palumbo et al. (2020).
Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque formation in Tg2576 mice.
Neuroscience, 2011

A mouse model of amyloid pathology was used to first examine using a cross sectional design changes in retrosplenial cortex activity in transgenic mice aged 5, 11, 17, and 23 months. Attention focused on: (1) overt amyloid labeled with β-amyloid((1-42)) and Congo Red staining, (2) metabolic function assessed by the enzyme, cytochrome oxidase, and (3) neuronal activity as assessed indirectly by the immediate-early gene (IEG), c-Fos. Changes in cytochrome oxidase and c-Fos activity were observed in the retrosplenial cortex in Tg2576 mice as early as 5 months of age, long before evidence of plaque formation. Subsequent analyses concentrating on this early dysfunction revealed at 5 months pervasive, amyloid precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex and selective afferents (anterior thalamus, hippocampus), which was associated with the observed c-Fos hyporeactivity. These findings indicate that retrosplenial cortex dysfunction occurs during early stages of amyloid production in Tg2576 mice and may contribute to cognitive dysfunction.
Dissecting the pathobiology of altered MRI signal in amyotrophic lateral sclerosis: A post mortem whole brain sampling strategy for the integration of ultra-high-field MRI and quantitative neuropathology.
BMC neuroscience, 2018

Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically. One route to understanding and validating the pathophysiological correlates of MRI signal changes in ALS is to directly compare MRI to histology in post mortem human brains.
Perceptual reversals during binocular rivalry: ERP components and their concomitant source differences.
Psychophysiology, 2011

We used an intermittent stimulus presentation to investigate event-related potential (ERP) components associated with perceptual reversals during binocular rivalry. The combination of spatiotemporal ERP analysis with source imaging and statistical parametric mapping of the concomitant source differences yielded differences in three time windows: reversals showed increased activity in early visual (∼120 ms) and in inferior frontal and anterior temporal areas (∼400-600 ms) and decreased activity in the ventral stream (∼250-350 ms). The combination of source imaging and statistical parametric mapping suggests that these differences were due to differences in generator strength and not generator configuration, unlike the initiation of reversals in right inferior parietal areas. These results are discussed within the context of the extensive network of brain areas that has been implicated in the initiation, implementation, and appraisal of bistable perceptual reversals.
Can adolescents learn self-control? Delay of gratification in the development of control over risk taking.
Prevention science : the official journal of the Society for Prevention Research, 2010

Recent findings from developmental neuroscience suggest that the adolescent brain is too immature to exert control over impulsive drives, such as sensation seeking, that increase during adolescence. Using a discounting of delayed reward paradigm, this research examines the ability to delay gratification as a potential source of control over risk-taking tendencies that increase during adolescence. In addition, it explores the role of experience resulting from risk taking as well as future time perspective as contributors to the development of this ability. In a nationally representative sample (n = 900) of young people aged 14-22, a structural equation analysis shows that risk taking as assessed by use of three popular drugs (tobacco, marijuana, and alcohol) is inversely related to the ability to delay gratification. The relation is robust across gender, age, and different levels of sensation seeking. In addition, high sensation seekers exhibit dramatic age-related increase in delay of gratification, lending support to the hypothesis that engaging in risky behavior provides experience that leads to greater patience for long-term rewards. The findings support the conclusion that a complete understanding of the development of self-control must consider individual differences not easily explained by universal trends in brain maturation.
Suicide rates in Iceland before and after the 2008 Global Recession: a nationwide population-based study.
European journal of public health, 2020

Economic downturns have been associated with increased suicide rates. The 2008 global financial crisis varied across countries but hit Iceland relatively hard. We aimed to study potential changes in suicide rates in Iceland during this major economic transition.
Aplysia Ganglia preparation for electrophysiological and molecular analyses of single neurons.
Journal of visualized experiments : JoVE, 2014

A major challenge in neurobiology is to understand the molecular underpinnings of neural circuitry that govern a specific behavior. Once the specific molecular mechanisms are identified, new therapeutic strategies can be developed to treat abnormalities in specific behaviors caused by degenerative diseases or aging of the nervous system. The marine snail Aplysia californica is well suited for the investigations of cellular and molecular basis of behavior because neural circuitry underlying a specific behavior could be easily determined and the individual components of the circuitry could be easily manipulated. These advantages of Aplysia have led to several fundamental discoveries of neurobiology of learning and memory. Here we describe a preparation of the Aplysia nervous system for the electrophysiological and molecular analyses of individual neurons. Briefly, ganglion dissected from the nervous system is exposed to protease to remove the ganglion sheath such that neurons are exposed but retain neuronal activity as in the intact animal. This preparation is used to carry out electrophysiological measurements of single or multiple neurons. Importantly, following the recording using a simple methodology, the neurons could be isolated directly from the ganglia for gene expression analysis. These protocols were used to carry out simultaneous electrophysiological recordings from L7 and R15 neurons, study their response to acetylcholine and quantitating expression of CREB1 gene in isolated single L7, L11, R15, and R2 neurons of Aplysia.
Flashbacks, intrusions, mind-wandering - Instances of an involuntary memory spectrum: A commentary on Takarangi, Strange, and Lindsay (2014).
Consciousness and cognition, 2015

In their paper, Takarangi, Strange, and Lindsay (2014) showed in two experiments that participants who had witnessed a shocking film frequently "mind-wandered without awareness" about the content of the film. More importantly, they equated this effect with the occurrence of traumatic intrusions. In this commentary, we argue that the authors adhered to conceptually ambiguous terms, and thereby unintentionally contribute to an already existing conceptual blur in the trauma-memory field. We postulate that clear definitions are urgently needed for phenomena such as intrusions, flashbacks, and mind-wandering, when using them in the context of trauma memory. Furthermore, our proposal is that these phenomena can fall under a spectrum of different involuntary memory instances. We propose that by adopting stricter definitions and viewing them as separate, but interrelated phenomena, different lines of trauma-memory research can be reconciled, which would considerably advance the field.
Morphometric and histologic substrates of cingulate integrity in elders with exceptional memory capacity.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

This human study is based on an established cohort of "SuperAgers," 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20-30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50-60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.
The Carotid Sinus Nerve-Structure, Function, and Clinical Implications.
Anatomical record (Hoboken, N.J. : 2007), 2019

Interest has been renewed in the anatomy and physiology of the carotid sinus nerve (CSN) and its targets (carotid sinus and carotid body, CB), due to recent proposals of surgical procedures for a series of common pathologies, such as carotid sinus syndrome, hypertension, heart failure, and insulin resistance. The CSN originates from the glossopharyngeal nerve soon after its appearance from the jugular foramen. It shows frequent communications with the sympathetic trunk (usually at the level of the superior cervical ganglion) and the vagal nerve (main trunk, pharyngeal branches, or superior laryngeal nerve). It courses on the anterior aspect of the internal carotid artery to reach the carotid sinus, CB, and/or intercarotid plexus. In the carotid sinus, type I (dynamic) carotid baroreceptors have larger myelinated A-fibers; type II (tonic) baroreceptors show smaller A- and unmyelinated C-fibers. In the CB, afferent fibers are mainly stimulated by acetylcholine and ATP, released by type I cells. The neurons are located in the petrosal ganglion, and centripetal fibers project on to the solitary tract nucleus: chemosensory inputs to the commissural subnucleus, and baroreceptor inputs to the commissural, medial, dorsomedial, and dorsolateral subnuclei. The baroreceptor component of the CSN elicits sympatho-inhibition and the chemoreceptor component stimulates sympatho-activation. Thus, in refractory hypertension and heart failure (characterized by increased sympathetic activity), baroreceptor electrical stimulation, and CB removal have been proposed. Instead, denervation of the carotid sinus has been proposed for the "carotid sinus syndrome." Anat Rec, 302:575-587, 2019. © 2018 Wiley Periodicals, Inc.
Divergent innervation of the olfactory bulb by distinct raphe nuclei.
The Journal of comparative neurology, 2015

The raphe nuclei provide serotonergic innervation widely in the brain, thought to mediate a variety of neuromodulatory effects. The mammalian olfactory bulb (OB) is a prominent recipient of serotonergic fibers, particularly in the glomerular layer (GL), where they are thought to gate incoming signals from the olfactory nerve. The dorsal raphe nucleus (DRN) and the median raphe nucleus (MRN) are known to densely innervate the OB. The majority of such projections are thought to terminate in the GL, but this has not been explicitly tested. We sought to investigate this using recombinant adeno-associated viruses (rAAV)-mediated expression of green fluorescent protein (GFP)-synaptophysin targeted specifically to neurons of the DRN or the MRN. With DRN injections, labeled fibers were found mostly in the granule cell layer (GCL), not the GL. Conversely, dense labeling in the GL was observed with MRN injections, suggesting that the source of GL innervation is the MRN, not the DRN, as previously thought. The two raphe nuclei thus give dual innervation within the OB, with distinct innervation patterns.
Effects of postnatal isolation rearing and antidepressant treatment on the density of serotonergic and noradrenergic axons and depressive behavior in rats.
Neuroscience, 2009

The development of monoaminergic axons is affected by pharmacological and environmental manipulations during early periods of brain development. In addition, it has been proposed that changes in the density of monoaminergic axons are involved in the pathophysiology of depression. The present experiments examined the effects of neonatal treatment with antidepressants on the density of monoaminergic axons containing 5-HT or noradrenaline (NA) and depressive behavior in rats. In this study, clomipramine (CL) was used as an antidepressant, because a large amount of data has been accumulated on the effects of neonatal CL treatment on monoaminergic neurons and depressive behavior. It was also examined whether the effects of neonatal CL treatment could be further modified by environmental conditions. In the present experiments, postweaning isolation rearing (Iso) was examined as an environmental condition, because postweaning Iso is reported to change the density of 5-HT axons in the rat brain. Unexpectedly, neonatal CL treatment alone had no effect on the density of 5-HT or NA axons or depressive behavior. Postweaning social Iso rearing reduced the density of 5-HT axons in the central nucleus and basolateral nucleus of the amygdala and CA3 of the hippocampus. In the prelimbic area and infralimbic area of medial prefrontal cortex and the dentate gyrus of the hippocampus, the density of 5-HT axons was not affected by social Iso alone, but was reduced when animals were socially isolated after neonatal CL treatment. Postweaning Iso, but not neonatal CL treatment, increased immobility in the forced swim test in adolescence/early adulthood. These findings suggest that postweaning social Iso alters the density of monoaminergic axons, particularly 5-HT axons, and induces a possible model of depression, while neonatal CL treatment alone has no effect on the density of NA or 5-HT axons or depressive behavior in adolescence/early adulthood.
Enhancing image quality in cleared tissue with adaptive optics.
Journal of biomedical optics, 2016

Our ability to see fine detail at depth in tissues is limited by scattering and other refractive characteristics of the tissue. For fixed tissue, we can limit scattering with a variety of clearing protocols. This allows us to see deeper but not necessarily clearer. Refractive aberrations caused by the bulk index of refraction of the tissue and its variations continue to limit our ability to see fine detail. Refractive aberrations are made up of spherical and other Zernike modes, which can be significant at depth. Spherical aberration that is common across the imaging field can be corrected using an objective correcting collar, although this can require manual intervention. Other aberrations may vary across the imaging field and can only be effectively corrected using adaptive optics. Adaptive optics can also correct other aberrations simultaneously with the spherical aberration, eliminating manual intervention and speeding imaging. We use an adaptive optics two-photon microscope to examine the impact of the spherical and higher order aberrations on imaging and contrast the effect of compensating only for spherical aberration against compensating for the first 22 Zernike aberrations in two tissue types. Increase in image intensity by 1.6× and reduction of root mean square error by 3× are demonstrated.
Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism.
PLoS biology, 2016

Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans.
Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition.
Behavioural brain research, 2016

The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n=27, ThrThr n=27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.