rudyvdbrink/CitationDatabase huggingface dataset:
D2 receptor occupancy in conscious rat brain is not significantly distinguished with [3H]-MNPA, [3H]-(+)-PHNO, and [3H]-raclopride.
Synapse (New York, N.Y.), 2010

Positron emission tomography (PET) antagonist ligands such as [(11)C]-raclopride are commonly used to study dopamine D2 receptor (D2) binding of antipsychotics. It has been suggested that agonist radioligands bind preferentially to the high-affinity state of D2 receptor and may provide a more relevant means of assessing D2 occupancy. The main objective of this study was to determine if D2 receptor occupancy (RO) could be differentiated with agonist and antagonist radioligands in vivo. Agonist radioligands [(3)H]-MNPA and [(3)H]-(+)-PHNO were synthesized and compared to antagonist [(3)H]-raclopride in the in vitro binding and in vivo occupancy studies. In vivo, unanesthetized rats were pretreated with quinpirole (full agonist), aripiprazole (partial agonist), or haloperidol (antagonist) prior to administration of the agonist or antagonist radioligand. All three pretreatment compounds showed equivalent dose-dependent D2 receptor occupancy in the rat striatum with each radioligand. The in vivo receptor occupancy results suggested that the binding of quinpirole, aripiprazole, and haloperidol to the high or low affinity state of the D2 receptor could not be differentiated using radiolabeled agonists or antagonists, presumably due to a predominance of high affinity states of the D2 receptor in vivo. This hypothesis was supported in part by the in vitro binding results. Our in vitro results show that [(3)H]-MNPA binds to D2S transfected CHO cell membranes at a single high affinity site. Displacement of [(3)H]-(+)-PHNO binding by quinpirole and elimination of most [(3)H]-(+)-PHNO binding by the guanine nucleotide GppNHp in striatal membranes suggest that the majority of D2 in striatal tissue is G-protein coupled. Together, these findings suggest that D2 agonist radioligands produce in vivo receptor occupancy comparable to [(3)H]-raclopride.
Response properties underlying selectivity for the rate of frequency modulated sweeps in the auditory cortex of the mouse.
Hearing research, 2013

This study focused on the response properties underlying selectivity for the rate of frequency modulated (FM) sweeps in the auditory cortex of anesthetized C57bl/6 (C57) mice. Linear downward FM sweeps with rates between 0.08 and 20 kHz/ms were tested. We show that at least two different response properties predict FM rate selectivity: sideband inhibition and duration tuning. Sideband inhibition was determined using the two-tone inhibition paradigm in which excitatory and inhibitory tones were presented with different delays. Sideband inhibition was present in the majority (88%, n = 53) of neurons. The spectrotemporal properties of sideband inhibition predicted rate selectivity and exclusion of the sideband from the sweep reduced/eliminated rate tuning. The second property predictive of sweep rate selectivity was duration tuning for tones. Theoretically, if a neuron is selective for the duration that a sweep spends in the excitatory frequency tuning curve, then rate selectivity will ensue. Duration tuning for excitatory tones was present and predicted rate selectivity in ∼34% of neurons (n = 97). Both sideband inhibition and duration tuning predicted rate selectivity equally well, but sideband inhibition was present in a larger percentage of neurons suggesting that it is the dominant mechanism in the C57 mouse auditory cortex. Similar mechanisms shape sweep rate selectivity in the auditory system of bats and mice and movement-velocity selectivity in the visual system, suggesting similar solutions to analogous problems across sensory systems. This study provides baseline data on basic spectrotemporal processing in the C57 strain for elucidation of changes that occur in presbycusis.
M1-muscarinic receptors promote fear memory consolidation via phospholipase C and the M-current.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Neuromodulators released during and after a fearful experience promote the consolidation of long-term memory for that experience. Because overconsolidation may contribute to the recurrent and intrusive memories of post-traumatic stress disorder, neuromodulatory receptors provide a potential pharmacological target for prevention. Stimulation of muscarinic receptors promotes memory consolidation in several conditioning paradigms, an effect primarily associated with the M1 receptor (M1R). However, neither inhibiting nor genetically disrupting M1R impairs the consolidation of cued fear memory. Using the M1R agonist cevimeline and antagonist telenzepine, as well as M1R knock-out mice, we show here that M1R, along with β2-adrenergic (β2AR) and D5-dopaminergic (D5R) receptors, regulates the consolidation of cued fear memory by redundantly activating phospholipase C (PLC) in the basolateral amygdala (BLA). We also demonstrate that fear memory consolidation in the BLA is mediated in part by neuromodulatory inhibition of the M-current, which is conducted by KCNQ channels and is known to be inhibited by muscarinic receptors. Manipulating the M-current by administering the KCNQ channel blocker XE991 or the KCNQ channel opener retigabine reverses the effects on consolidation caused by manipulating β2AR, D5R, M1R, and PLC. Finally, we show that cAMP and protein kinase A (cAMP/PKA) signaling relevant to this stage of consolidation is upstream of these neuromodulators and PLC, suggesting an important presynaptic role for cAMP/PKA in consolidation. These results support the idea that neuromodulatory regulation of ion channel activity and neuronal excitability is a critical mechanism for promoting consolidation well after acquisition has occurred.
Parkinson's disease: in vivo metabolic changes in the frontal and parietal cortices in 6-OHDA treated rats during different periods.
The International journal of neuroscience, 2014

This study aims to investigate metabolic changes in frontal and parietal cortices in the 6-OHDA induced Parkinson's rats. Ratios of N-acetyl-aspartic acid/creatine (NAA/Cr), choline/creatine (Cho/Cr), and glumatic acid and glutamine glutaminic acid/creatine (Glx/Cr) of regions of interests (ROIs) in the frontal and parietal cortices, and the substantia nigra were analyzed. NAA/Cr, Cho/Cr and Glx/Cr in the frontal and parietal cortices in the lesion side did not show any significant differences two weeks after operation compared with the contralateral side (p > 0.05). NAA/Cr in the frontal cortex in the lesion side was significantly lower in the five weeks after operation; Cho/Cr remained normal; Glx/Cr increased (p < 0.05), and all ratios of parietal cortex were normal. In the eight weeks after operation, NAA/Cr in the frontal cortex in the lesion side was lower than that of the five weeks (p < 0.01), Cho/Cr still remained normal while Glx/Cr was higher than before (p < 0.01). Regarding the parietal cortex, NAA/Cr increased significantly, while Cho/Cr and Glx/Cr remained normal. In the 12 weeks after operation, NAA/Cr, Cho/Cr and Glx/Cr in frontal cortex were consistent with that of the eight weeks, while they remained at the normal level in parietal cortex. The NAA/Cr in the substantia nigra decreased and Cho/Cr increased significantly during 2-8 weeks, and remained at the same level during 8-12 weeks. There are metabolic disturbances in PD rats. The transient hyperfunction in the parietal cortex can be considered as a compensation for the dysfunction of the frontal cortex and substantia nigra.
The biological origins of rituals: An interdisciplinary perspective.
Neuroscience and biobehavioral reviews, 2019

Ritual behavior is ubiquitous, marking animal motor patterns, normal and psychopathological behavior in human individuals as well as every human culture. Moreover, formal features of rituals appear to be highly conserved along phylogeny and characterized by a circular and spatio-temporal structure typical of habitual behavior with internal repetition of non-functional acts and redirection of attention to the "script" of the performance. A continuity, based on highly conserved cortico-striatal loops, can be traced from animal rituals to human individual and collective rituals with psychopathological compulsions at the crossing point. The transition from "routinization" to "ritualization" may have been promoted to deal with environmental unpredictability in non-social contexts and, through motor synchronization, to enhance intra-group cohesion and communication in social contexts. Ultimately, ritual, following its biological constraints exerts a "homeostatic" function on the environment (social and non-social) under conditions of unpredictability.
Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.
NeuroImage, 2011

Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.
Maternal Inflammation and Neurodevelopmental Programming: A Review of Preclinical Outcomes and Implications for Translational Psychiatry.
Biological psychiatry, 2019

Early disruptions to neurodevelopment are highly relevant to understanding both psychiatric risk and underlying pathophysiology that can be targeted by new treatments. Much convergent evidence from the human literature associates inflammation during pregnancy with later neuropsychiatric disorders in offspring. Preclinical models of prenatal inflammation have been developed to examine the causal maternal physiological and offspring neural mechanisms underlying these findings. Here we review the strengths and limitations of preclinical models used for these purposes and describe selected studies that have shown maternal immune impacts on the brain and behavior of offspring. Maternal immune activation in mice, rats, nonhuman primates, and other mammalian model species have demonstrated convergent outcomes across methodologies. These outcomes include shifts and/or disruptions in the normal developmental trajectory of molecular and cellular processes in the offspring brain. Prenatal developmental origins are critical to a mechanistic understanding of maternal immune activation-induced alterations to microglia and immune molecules, brain growth and development, synaptic morphology and physiology, and anxiety- and depression-like, sensorimotor, and social behaviors. These phenotypes are relevant to brain functioning across domains and to anxiety and mood disorders, schizophrenia, and autism spectrum disorder, in which they have been identified. By turning a neurodevelopmental lens on this body of work, we emphasize the importance of acute changes to the prenatal offspring brain in fostering a better understanding of potential mechanisms for intervention. Collectively, overlapping results across maternal immune activation studies also highlight the need to examine preclinical offspring neurodevelopment alterations in terms of a multifactorial immune milieu, or immunome, to determine potential mechanisms of psychiatric risk.
The sifting of visual information in the superior colliculus.
eLife, 2020

Much of the early visual system is devoted to sifting the visual scene for the few bits of behaviorally relevant information. In the visual cortex of mammals, a hierarchical system of brain areas leads eventually to the selective encoding of important features, like faces and objects. Here, we report that a similar process occurs in the other major visual pathway, the superior colliculus. We investigate the visual response properties of collicular neurons in the awake mouse with large-scale electrophysiology. Compared to the superficial collicular layers, neuronal responses in the deeper layers become more selective for behaviorally relevant stimuli; more invariant to location of stimuli in the visual field; and more suppressed by repeated occurrence of a stimulus in the same location. The memory of familiar stimuli persists in complete absence of the visual cortex. Models of these neural computations lead to specific predictions for neural circuitry in the superior colliculus.
Hybrid PET/MRI enables high-spatial resolution, quantitative imaging of amyloid plaques in an Alzheimer's disease mouse model.
Scientific reports, 2020

The emergence of PET probes for amyloid plaques and neurofibrillary tangles, hallmarks of Alzheimer disease (AD), enables monitoring of pathology in AD mouse models. However, small-animal PET imaging is limited by coarse spatial resolution. We have installed a custom-fabricated PET insert into our small-animal MRI instrument and used PET/MRI hybrid imaging to define regions of amyloid vulnerability in 5xFAD mice. We compared fluorine-18 [
Inferring functional connectivity in MRI using Bayesian network structure learning with a modified PC algorithm.
NeuroImage, 2013

Resting state functional connectivity MRI (rs-fcMRI) is a popular technique used to gauge the functional relatedness between regions in the brain for typical and special populations. Most of the work to date determines this relationship by using Pearson's correlation on BOLD fMRI timeseries. However, it has been recognized that there are at least two key limitations to this method. First, it is not possible to resolve the direct and indirect connections/influences. Second, the direction of information flow between the regions cannot be differentiated. In the current paper, we follow-up on recent work by Smith et al. (2011), and apply PC algorithm to both simulated data and empirical data to determine whether these two factors can be discerned with group average, as opposed to single subject, functional connectivity data. When applied on simulated individual subjects, the algorithm performs well determining indirect and direct connection but fails in determining directionality. However, when applied at group level, PC algorithm gives strong results for both indirect and direct connections and the direction of information flow. Applying the algorithm on empirical data, using a diffusion-weighted imaging (DWI) structural connectivity matrix as the baseline, the PC algorithm outperformed the direct correlations. We conclude that, under certain conditions, the PC algorithm leads to an improved estimate of brain network structure compared to the traditional connectivity analysis based on correlations.
Inherited leukoencephalopathies with clinical onset in middle and old age.
Journal of the neurological sciences, 2014

The currently widespread use of neuroimaging has led neurologists to often face the problem of the differential diagnosis of white matter diseases. There are various forms of leukoencephalopathies (vascular, inflammatory and immunomediated, infectious, metabolic, neoplastic) and sometimes white matter lesions are expression of a genetic disease. While many inherited leukoencephalopathies fall in the child neurologist's interest, others may have a delayed or even a typical onset in the middle or old age. This field is rapidly growing and, in the last few years, many new inherited white matter diseases have been described and genetically defined. A non-delayed recognition of middle and old age inherited leukoencephalopathies appears important to avoid unnecessary tests and therapies in the patient and to possibly anticipate the diagnosis in relatives. The aim of this review is to provide a guide to direct the diagnostic process when facing a patient with a suspicion of an inherited form of leukoencephalopathy and with clinical onset in middle or old age. Based on a MEDLINE search from 1990 to 2013, we identified 24 middle and old age onset inherited leukoencephalopathies and reviewed in this relation the most recent findings focusing on their differential diagnosis. We provide summary tables to use as a check list of clinical and neuroimaging findings that are most commonly associated with these forms of leukoencephalopathies. When present, we reported specific characteristics of single diseases. Several genetic diseases may be suspected in patients with middle or old age and white matter abnormalities. In only few instances, pathognomonic clinical or associated neuroimaging features help identifying a specific disease. Therefore, a comprehensive knowledge of the characteristics of these inherited white matter diseases appears important to improve the diagnostic work-up, optimize the choice of genetic tests, increase the number of diagnosed patients, and stimulate the research interest in this field.
HDAC6 is a Bruchpilot deacetylase that facilitates neurotransmitter release.
Cell reports, 2014

Presynaptic densities are specialized structures involved in synaptic vesicle tethering and neurotransmission; however, the mechanisms regulating their function remain understudied. In Drosophila, Bruchpilot is a major constituent of the presynaptic density that tethers vesicles. Here, we show that HDAC6 is necessary and sufficient for deacetylation of Bruchpilot. HDAC6 expression is also controlled by TDP-43, an RNA-binding protein deregulated in amyotrophic lateral sclerosis (ALS). Animals expressing TDP-43 harboring pathogenic mutations show increased HDAC6 expression, decreased Bruchpilot acetylation, larger vesicle-tethering sites, and increased neurotransmission, defects similar to those seen upon expression of HDAC6 and opposite to hdac6 null mutants. Consequently, reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion. Our work identifies HDAC6 as a Bruchpilot deacetylase and indicates that regulating acetylation of a presynaptic release-site protein is critical for maintaining normal neurotransmission.
Corresponding ECoG and fMRI category-selective signals in human ventral temporal cortex.
Neuropsychologia, 2016

Functional magnetic resonance imaging (fMRI) and electrocorticography (ECoG) research have been influential in revealing the functional characteristics of category-selective responses in human ventral temporal cortex (VTC). One important, but unanswered, question is how these two types of measurements might be related with respect to the VTC. Here we examined which components of the ECoG signal correspond to the fMRI response by using a rare opportunity to measure both fMRI and ECoG responses from the same individuals to images of exemplars of various categories including faces, limbs, cars and houses. Our data reveal three key findings. First, we discovered that the coupling between fMRI and ECoG responses is frequency and time dependent. The strongest and most sustained correlation is observed between fMRI and high frequency broadband (HFB) ECoG responses (30-160 hz). In contrast, the correlation between fMRI and ECoG signals in lower frequency bands is temporally transient, where the correlation is initially positive, but then tapers off or becomes negative. Second, we find that the strong and positive correlation between fMRI and ECoG signals in all frequency bands emerges rapidly around 100 ms after stimulus onset, together with the onset of the first stimulus-driven neural signals in VTC. Third, we find that the spatial topology and representational structure of category-selectivity in VTC reflected in ECoG HFB responses mirrors the topology and structure observed with fMRI. These findings of a strong and rapid coupling between fMRI and HFB responses validate fMRI measurements of functional selectivity with recordings of direct neural activity and suggest that fMRI category-selective signals in VTC are associated with feed-forward neural processing.
Implicit sequence learning in ring-tailed lemurs (Lemur catta).
Journal of the experimental analysis of behavior, 2016

Implicit learning involves picking up information from the environment without explicit instruction or conscious awareness of the learning process. In nonhuman animals, conscious awareness is impossible to assess, so we define implicit learning as occurring when animals acquire information beyond what is required for successful task performance. While implicit learning has been documented in some nonhuman species, it has not been explored in prosimian primates. Here we ask whether ring-tailed lemurs (Lemur catta) learn sequential information implicitly. We tested lemurs in a modified version of the serial reaction time task on a touch screen computer. Lemurs were required to respond to any picture within a 2 × 2 grid of pictures immediately after its surrounding border flickered. Over 20 training sessions, both the locations and the identities of the images remained constant and response times gradually decreased. Subsequently, the locations and/or the identities of the images were disrupted. Response times indicated that the lemurs had learned the physical location sequence required in original training but did not learn the identity of the images. Our results reveal that ring-tailed lemurs can implicitly learn spatial sequences, and raise questions about which scenarios and evolutionary pressures give rise to perceptual versus motor-implicit sequence learning.
Spatial and temporal characteristics of vestibular convergence.
Neuroscience, 2011

In all species studied, afferents from semicircular canals and otolith organs converge on central neurons in the brainstem. However, the spatial and temporal relationships between converging inputs and how these contribute to vestibular behaviors is not well understood. In the current study, we used discrete rotational and translational motion stimuli to characterize canal- and otolith-driven response components of convergent non-eye movement (NEM) neurons in the vestibular nuclear complex of alert pigeons. When compared to afferent responses, convergent canal signals had similar gain and phase ranges but exhibited greater spatial variability in their axes of preferred rotation. Convergent otolith signals also had similar mean gain and phase values to the afferent population but were spatially well-matched with the corresponding canal signals, cell-by-cell. However, neither response component alone nor a simple linear combination of these components was sufficient to predict actual net responses during combined canal-otolith stimulation. We discuss these findings in the context of previous studies of pigeon vestibular behaviors, and we compare our findings to similar studies in other species.