bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-Grounded Vision: Hand Ownership Modulates Visual Location through Cortical β and γ Oscillations
Authors: Faivre Nathan , Dönz Jonathan , Scandola Michele , Dhanis Herberto , Bello Ruiz Javier , Bernasconi Fosco , Salomon Roy , Blanke Olaf 
Published: November 2016

Vision is known to be shaped by context, defined by environmental and bodily signals. In the Taylor illusion, the size of an afterimage projected on one's hand changes according to proprioceptive signals conveying hand position. Here, we assessed whether the Taylor illusion does not just depend on the physical hand position, but also on bodily self-consciousness as quantified through illusory hand ownership. Relying on the somatic rubber hand illusion, we manipulated hand ownership, such that participants embodied a rubber hand placed next to their own hand. We found that an afterimage projected on the participant's hand drifted depending on illusory ownership between the participants' two hands, showing an implication of self-representation during the Taylor illusion. Oscillatory power analysis of electroencephalographic signals showed that illusory hand ownership was stronger in participants with stronger α suppression over left sensorimotor cortex, whereas the Taylor illusion correlated with higher β/γ power over frontotemporal regions. Higher γ connectivity between left sensorimotor and inferior parietal cortex was also found during illusory hand ownership. These data show that afterimage drifts in the Taylor illusion do not only depend on the physical hand position but also on subjective ownership, which itself is based on the synchrony of somatosensory signals from the two hands. The effect of ownership on afterimage drifts is associated with β/γ power and γ connectivity between frontoparietal regions and the visual cortex. Together, our results suggest that visual percepts are not only influenced by bodily context but are self-grounded, mapped on a self-referential frame.SIGNIFICANCE STATEMENTVision is influenced by the body: in the Taylor illusion, the size of an afterimage projected on one's hand changes according to tactile and proprioceptive signals conveying hand position. Here, we report a new phenomenon revealing that the perception of afterimages depends not only on bodily signals, but also on the sense of self. Relying on the rubber hand illusion, we manipulated hand ownership, so that participants embodied a rubber hand placed next to their own hand. We found that visual afterimages projected on the participant's hand drifted laterally, only when the rubber hand was embodied. Electroencephalography revealed spectral dissociations between somatic and visual effects, and higher γ connectivity along the dorsal visual pathways when the rubber hand was embodied.
DrosophilaDH31 Neuropeptide and PDF Receptor Regulate Night-Onset Temperature Preference
Authors: Goda Tadahiro , Tang Xin , Umezaki Yujiro , Chu Michelle L. , Kunst Michael , Nitabach Michael N. , Hamada Fumika N. 
Published: November 2016

Body temperature exhibits rhythmic fluctuations over a 24 h period (Refinetti and Menaker, 1992) and decreases during the night, which is associated with sleep initiation (Gilbert et al., 2004; Kräuchi, 2007a,b). However, the underlying mechanism of this temperature decrease is largely unknown. We have previously shown thatDrosophilaexhibit a daily temperature preference rhythm (TPR), in which their preferred temperatures increase during the daytime and then decrease at the transition from day to night (night-onset) (Kaneko et al., 2012). BecauseDrosophilaare small ectotherms, their body temperature is very close to that of the ambient temperature (Stevenson, 1985), suggesting that their TPR generates their body temperature rhythm. Here, we demonstrate that the neuropeptide diuretic hormone 31 (DH31) and pigment-dispersing factor receptor (PDFR) contribute to regulate the preferred temperature decrease at night-onset. We show that PDFR and tethered-DH31 expression in dorsal neurons 2 (DN2s) restore the preferred temperature decrease at night-onset, suggesting that DH31 acts on PDFR in DN2s. Notably, we previously showed that the molecular clock in DN2s is important for TPR. Although PDF (another ligand of PDFR) is a critical factor for locomotor activity rhythms,Pdfmutants exhibit normal preferred temperature decreases at night-onset. This suggests that DH31-PDFR signaling specifically regulates a preferred temperature decrease at night-onset. Thus, we propose that night-onset TPR and locomotor activity rhythms are differentially controlled not only by clock neurons but also by neuropeptide signaling in the brain.SIGNIFICANCE STATEMENTBody temperature rhythm (BTR) is fundamental for the maintenance of functions essential for homeostasis, such as generating metabolic energy and sleep. One major unsolved question is how body temperature decreases dramatically during the night. Previously, we demonstrated that a BTR-like mechanism, referred to as temperature preference rhythm (TPR), exists inDrosophila. Here, we demonstrate that the diuretic hormone 31 (DH31) neuropeptide and pigment-dispersing factor receptor (PDFR) regulate preferred temperature decreases at night-onset via dorsal neurons 2. This is the firstin vivoevidence that DH31 could function as a ligand of PDFR. Although both DH31 and PDF are ligands of PDFR, we show that DH31 regulates night-onset TPR, but PDF does not, suggesting that night-onset TPR and locomotor activity rhythms are controlled by different neuropeptides via different clock cells.
Mutant α-Synuclein Overexpression Induces Stressless Pacemaking in Vagal Motoneurons at Risk in Parkinson's Disease
Authors: Lasser-Katz Efrat , Simchovitz Alon , Chiu Wei-Hua , Oertel Wolfgang H. , Sharon Ronit , Soreq Hermona , Roeper Jochen , Goldberg Joshua A. 
Published: November 2016

α-Synuclein overexpression (ASOX) drives the formation of toxic aggregates in neurons vulnerable in Parkinson's disease (PD), including dopaminergic neurons of the substantia nigra (SN) and cholinergic neurons of the dorsal motor nucleus of the vagus (DMV). Just as these populations differ in when they exhibit α-synucleinopathies during PD pathogenesis, they could also differ in their physiological responses to ASOX. An ASOX-mediated hyperactivity of SN dopamine neurons, which was caused by oxidative dysfunction of Kv4.3 potassium channels, was recently identified in transgenic (A53T-SNCA) mice overexpressing mutated human α-synuclein. Noting that DMV neurons display extensive α-synucleinopathies earlier than SN dopamine neurons while exhibiting milder cell loss in PD, we aimed to define the electrophysiological properties of DMV neurons inA53T-SNCAmice. We found that DMV neurons maintain normal firing rates in response to ASOX. Moreover, Kv4.3 channels in DMV neurons exhibit no oxidative dysfunction in theA53T-SNCAmice, which could only be recapitulated in wild-type mice by glutathione dialysis. Two-photon imaging of redox-sensitive GFP corroborated the finding that mitochondrial oxidative stress was diminished in DMV neurons in theA53T-SNCAmice. This reduction in oxidative stress resulted from a transcriptional downregulation of voltage-activated (Cav) calcium channels in DMV neurons, which led to a reduction in activity-dependent calcium influx via Cav channels. Thus, ASOX induces a homeostatic remodeling with improved redox signaling in DMV neurons, which could explain the differential vulnerability of SN dopamine and DMV neurons in PD and could promote neuroprotective strategies that emulate endogenous homeostatic responses to ASOX (e.g., stressless pacemaking) in DMV neurons.SIGNIFICANCE STATEMENTOverexpression of mutant α-synuclein causes Parkinson's disease, presumably by driving neurodegeneration in vulnerable neuronal target populations. However, the extent of α-synuclein pathology (e.g., Lewy bodies) is not directly related to the degree of neurodegeneration across various vulnerable neuronal populations. Here, we show that, in contrast to dopamine neurons in the substantia nigra, vagal motoneurons do not enhance their excitability and oxidative load in response to chronic mutant α-synuclein overexpression. Rather, by downregulating their voltage-activated calcium channels, vagal motoneurons acquire a stressless form of pacemaking that diminishes mitochondrial and cytosolic oxidative stress. Emulating this endogenous adaptive response to α-synuclein overexpression could lead to novel strategies to protect dopamine neurons and perhaps delay the onset of Parkinson's disease.
Amyloid-β Peptide Nitrotyrosination Stabilizes Oligomers and Enhances NMDAR-Mediated Toxicity
Authors: Guivernau Biuse , Bonet Jaume , Valls-Comamala Victòria , Bosch-Morató Mònica , Godoy Juan A. , Inestrosa Nibaldo C. , Perálvarez-Marín Alex , Fernández-Busquets Xavier , Andreu David , Oliva Baldomero , Muñoz Francisco J. 
Published: November 2016

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the pathological aggregation of the amyloid-β peptide (Aβ). Monomeric soluble Aβ can switch from helicoidal to β-sheet conformation, promoting its assembly into oligomers and subsequently to amyloid fibrils. Oligomers are highly toxic to neurons and have been reported to induce synaptic transmission impairments. The progression from oligomers to fibrils forming senile plaques is currently considered a protective mechanism to avoid the presence of the highly toxic oligomers. Protein nitration is a frequent post-translational modification under AD nitrative stress conditions. Aβ can be nitrated at tyrosine 10 (Y10) by peroxynitrite. Based on our analysis of ThT binding, Western blot and electron and atomic force microscopy, we report that Aβ nitration stabilizes soluble, highly toxic oligomers and impairs the formation of fibrils. We propose a mechanism by which fibril elongation is interrupted upon Y10 nitration: Nitration disrupts fibril-forming folds by preventing H14-mediated bridging, as shown with an Aβ analog containing a single residue (H to E) replacement that mimics the behavior of nitrated Aβ related to fibril formation and neuronal toxicity. The pathophysiological role of our findings in AD was highlighted by the study of these nitrated oligomers on mouse hippocampal neurons, where an increased NMDAR-dependent toxicity of nitrated Aβ oligomers was observed. Our results show that Aβ nitrotyrosination is a post-translational modification that increases Aβ synaptotoxicity.SIGNIFICANCE STATEMENTWe report that nitration (i.e., the irreversible addition of a nitro group) of the Alzheimer-related peptide amyloid-β (Aβ) favors the stabilization of highly toxic oligomers and inhibits the formation of Aβ fibrils. The nitrated Aβ oligomers are more toxic to neurons due to increased cytosolic calcium levels throughout their action on NMDA receptors. Sustained elevated calcium levels trigger excitotoxicity, a characteristic event in Alzheimer's disease.
Neural Correlates of Fear in the Periaqueductal Gray
Authors: Watson Thomas C. , Cerminara Nadia L. , Lumb Bridget M. , Apps Richard 
Published: November 2016

The dorsal and ventral periaqueductal gray (dPAG and vPAG, respectively) are embedded in distinct survival networks that coordinate, respectively, innate and conditioned fear-evoked freezing. However, the information encoded by the PAG during these survival behaviors is poorly understood. Recordings in the dPAG and vPAG in rats revealed differences in neuronal activity associated with the two behaviors. During innate fear, neuronal responses were significantly greater in the dPAG compared with the vPAG. After associative fear conditioning and during early extinction (EE), when freezing was maximal, a field potential was evoked in the PAG by the auditory fear conditioned stimulus (CS). With repeated presentations of the unreinforced CS, animals displayed progressively less freezing accompanied by a reduction in event-related field potential amplitude. During EE, the majority of dPAG and vPAG units increased their firing frequency, but spike-triggered averaging showed that only ventral activity during the presentation of the CS was significantly coupled to EMG-related freezing behavior. This PAG–EMG coupling was only present for the onset of freezing activity during the CS in EE. During late extinction, a subpopulation of units in the dPAG and vPAG continued to show CS-evoked responses; that is, they were extinction resistant. Overall, these findings support roles for the dPAG in innate and conditioned fear and for the vPAG in initiating but not maintaining the drive to muscles to generate conditioned freezing. The existence of extinction-susceptible and extinction-resistant cells also suggests that the PAG plays a role in encoding fear memories.SIGNIFICANCE STATEMENTThe periaqueductal gray (PAG) orchestrates survival behaviors, with the dorsal (dPAG) and ventral (vPAG) PAG concerned respectively with innate and learnt fear responses. We recorded neural activity from dPAG and vPAG in rats during the expression of innate fear and extinction of learned freezing. Cells in dPAG responded more robustly during innate fear, but dPAG and vPAG both encoded the time of the conditioned stimulus during early extinction and displayed extinction sensitive and resistant characteristics. Only vPAG discharge was correlated with muscle activity, but this was limited to the onset of conditioned freezing. The data suggest that the roles of dPAG and vPAG in fear behavior are more complex than previously thought, including a potential role in fear memory.
Disruption of Glucagon-Like Peptide 1 Signaling inSim1Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress
Authors: Ghosal Sriparna , Packard Amy E.B. , Mahbod Parinaz , McKlveen Jessica M. , Seeley Randy J. , Myers Brent , Ulrich-Lai Yvonne , Smith Eric P. , D'Alessio David A. , Herman James P. 
Published: November 2016

Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediatedGlp1rknockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress. In addition, regionalGlp1rknockdown attenuated stress-induced cardiovascular responses accompanied by decreased sympathetic drive to the heart. Finally,Glp1rknockdown reduced anxiety-like behavior, implicating PVN GLP-1 signaling in behavioral stress reactivity. Collectively, these findings support a circuit whereby brainstem GLP-1 activates PVN signaling to mount an appropriate whole-organism response to stress. These results raise the possibility that dysfunction of this system may contribute to stress-related pathologies, and thereby provide a novel target for intervention.SIGNIFICANCE STATEMENTDysfunctional stress responses are linked to a number of somatic and psychiatric diseases, emphasizing the importance of precise neuronal control of effector pathways. Pharmacological evidence suggests a role for glucagon-like peptide-1 (GLP-1) in modulating stress responses. Using a targeted knockdown of the GLP-1 receptor in the single-minded 1 neurons, we show dependence of paraventricular nucleus GLP-1 signaling in the coordination of neuroendocrine, autonomic, and behavioral responses to acute and chronic stress. To our knowledge, this is the first direct demonstration of an obligate brainstem-to-hypothalamus circuit orchestrating general stress excitation across multiple effector systems. These findings provide novel information regarding signaling pathways coordinating central control of whole-body stress reactivity.
Fatty Acid-Binding Protein 5 at the Blood–Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function
Authors: Pan Yijun , Short Jennifer L. , Choy Kwok H. C. , Zeng Annie X. , Marriott Philip J. , Owada Yuji , Scanlon Martin J. , Porter Christopher J. H. , Nicolazzo Joseph A. 
Published: November 2016

Fatty acid-binding protein 5 (FABP5) at the blood–brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5+/+and FABP5−/−mice using a battery of memory paradigms. FABP5−/−mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood–brain barrier transport of DHA was assessed by measuring14C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5+/+and FABP5−/−mice. In line with a crucial role of FABP5 in the brain uptake of DHA,14C-DHA uptake into brain endothelial cells and brain capillaries of FABP5−/−mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5+/+mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5−/−mice are associated with reduced CNS access of DHA.SIGNIFICANCE STATEMENTGenetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5−/−mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role for FABP5 in the maintenance of cognitive function via regulating the brain uptake of DHA, and suggests that upregulation of FABP5 in neurodegenerative diseases, where brain DHA levels are possibly diminished (e.g., Alzheimer's disease), may provide a novel therapeutic approach for restoring cognitive function.
Neural Variability Quenching Predicts Individual Perceptual Abilities
Authors: Arazi Ayelet , Censor Nitzan , Dinstein Ilan 
Published: November 2016

Neural activity during repeated presentations of a sensory stimulus exhibits considerable trial-by-trial variability. Previous studies have reported that trial-by-trial neural variability is reduced (quenched) by the presentation of a stimulus. However, the functional significance and behavioral relevance of variability quenching and the potential physiological mechanisms that may drive it have been studied only rarely. Here, we recorded neural activity with EEG as subjects performed a two-interval forced-choice contrast discrimination task. Trial-by-trial neural variability was quenched by ∼40% after the presentation of the stimulus relative to the variability apparent before stimulus presentation, yet there were large differences in the magnitude of variability quenching across subjects. Individual magnitudes of quenching predicted individual discrimination capabilities such that subjects who exhibited larger quenching had smaller contrast discrimination thresholds and steeper psychometric function slopes. Furthermore, the magnitude of variability quenching was strongly correlated with a reduction in broadband EEG power after stimulus presentation. Our results suggest that neural variability quenching is achieved by reducing the amplitude of broadband neural oscillations after sensory input, which yields relatively more reproducible cortical activity across trials and enables superior perceptual abilities in individuals who quench more.SIGNIFICANCE STATEMENTVariability quenching is a phenomenon in which neural variability across trials is reduced by the presentation of a stimulus. Although this phenomenon has been reported across a variety of animal and human studies, its functional significance and behavioral relevance have been examined only rarely. Here, we report novel empirical evidence from humans revealing that variability quenching differs dramatically across individual subjects and explains to a certain degree why some individuals exhibit better perceptual abilities than others. In addition, we found a strong relationship between variability quenching and suppression of broadband neural oscillations. Together, our results reveal the importance of reproducible cortical activity for enabling better perceptual abilities and suggest a potential underlying mechanism that may explain why variability quenching occurs.
Somatic and Reinforcement-Based Plasticity in the Initial Stages of Human Motor Learning
Authors: Sidarta Ananda , Vahdat Shahabeddin , Bernardi Nicolò F. , Ostry David J. 
Published: November 2016

As one learns to dance or play tennis, the desired somatosensory state is typically unknown. Trial and error is important as motor behavior is shaped by successful and unsuccessful movements. As an experimental model, we designed a task in which human participants make reaching movements to a hidden target and receive positive reinforcement when successful. We identified somatic and reinforcement-based sources of plasticity on the basis of changes in functional connectivity using resting-state fMRI before and after learning. The neuroimaging data revealed reinforcement-related changes in both motor and somatosensory brain areas in which a strengthening of connectivity was related to the amount of positive reinforcement during learning. Areas of prefrontal cortex were similarly altered in relation to reinforcement, with connectivity between sensorimotor areas of putamen and the reward-related ventromedial prefrontal cortex strengthened in relation to the amount of successful feedback received. In other analyses, we assessed connectivity related to changes in movement direction between trials, a type of variability that presumably reflects exploratory strategies during learning. We found that connectivity in a network linking motor and somatosensory cortices increased with trial-to-trial changes in direction. Connectivity varied as well with the change in movement direction following incorrect movements. Here the changes were observed in a somatic memory and decision making network involving ventrolateral prefrontal cortex and second somatosensory cortex. Our results point to the idea that the initial stages of motor learning are not wholly motor but rather involve plasticity in somatic and prefrontal networks related both to reward and exploration.SIGNIFICANCE STATEMENTIn the initial stages of motor learning, the placement of the limbs is learned primarily through trial and error. In an experimental analog, participants make reaching movements to a hidden target and receive positive feedback when successful. We identified sources of plasticity based on changes in functional connectivity using resting-state fMRI. The main finding is that there is a strengthening of connectivity between reward-related prefrontal areas and sensorimotor areas in the basal ganglia and frontal cortex. There is also a strengthening of connectivity related to movement exploration in sensorimotor circuits involved in somatic memory and decision making. The results indicate that initial stages of motor learning depend on plasticity in somatic and prefrontal networks related to reward and exploration.