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Most vertebrates use head and eye movements to quickly change gaze orientation and sample different portions of the environment with periods of stable fixation. Visual information must be integrated across fixations to construct a complete perspective of the visual environment. In concert with this sampling strategy, neurons adapt to unchanging input to conserve energy and ensure that only novel information from each fixation is processed. We demonstrate how adaptation recovery times and saccade properties interact and thus shape spatiotemporal tradeoffs observed in the motor and visual systems of mice, cats, marmosets, macaques, and humans. These tradeoffs predict that in order to achieve similar visual coverage over time, animals with smaller receptive field sizes require faster saccade rates. Indeed, we find comparable sampling of the visual environment by neuronal populations across mammals when integrating measurements of saccadic behavior with receptive field sizes and V1 neuronal density. We propose that these mammals share a common statistically driven strategy of maintaining coverage of their visual environment over time calibrated to their respective visual system characteristics., (Copyright © 2024 Samonds et al.)

Hypertension augments while exercise training corrects the increased vesicle trafficking (transcytosis) across the blood-brain barrier (BBB) within preautonomic areas and the autonomic imbalance. There is no information on a possible mechanism(s) conditioning these effects. Knowing that Mfsd2a is the major transporter of docosahexaenoic acid (DHA) and that Mfsd2a knockout mice exhibited leaky BBB, we sought to identify its possible involvement in hypertension- and exercise-induced transcytosis across the BBB. Spontaneously hypertensive rats (SHR) and Wistar rats were submitted to treadmill training (T) or kept sedentary (S) for 4 wk. Resting hemodynamic/autonomic parameters were recorded in conscious chronically cannulated rats. BBB permeability within the hypothalamic paraventricular nucleus (PVN) was evaluated in anesthetized rats. Brains were harvested for Mfsd2a and caveolin-1 (an essential protein for vesicle formation) expression. SHR-S versus Wistar-S exhibited elevated arterial pressure (AP) and heart rate (HR), increased vasomotor sympathetic activity, reduced cardiac parasympathetic activity, greater pressure variability, reduced HR variability, and depressed baroreflex control. SHR-S also showed increased BBB permeability, reduced Mfsd2a, and increased caveolin-1 expression. SHR-T versus SHR-S exhibited increased Mfsd2a density, reduced caveolin-1 protein expression, and normalized PVN BBB permeability, which were accompanied by resting bradycardia, partial AP drop, reduced sympathetic and normalized cardiac parasympathetic activity, increased HR variability, and reduced pressure variability. No changes were observed in Wistar-T versus Wistar-S. Training is an efficient tool to rescue Mfsd2a expression, which by transporting DHA into the endothelial cell reduces caveolin-1 availability and vesicles' formation. Exercise-induced Mfsd2a normalization is an important mechanism to correct both BBB function and autonomic control in hypertensive subjects.

Heart failure (HF) is characterized by reduced ventricular function, compensatory activation of neurohormonal mechanisms and marked autonomic imbalance. Exercise training (T) is effective to reduce neurohormonal activation but the mechanism underlying the autonomic dysfunction remains elusive. Knowing that blood-brain barrier (BBB) lesion contributes to autonomic imbalance, we sought now to investigate its involvement in HF- and exercise-induced changes of autonomic control. Wistar rats submitted to coronary artery ligation or SHAM surgery were assigned to T or sedentary (S) protocol for 8 weeks. After hemodynamic/autonomic recordings and evaluation of BBB permeability, brains were harvesting for ultrastructural analysis of BBB constituents, measurement of vesicles trafficking and tight junction's (TJ) tightness across the BBB (transmission electron microscopy) and caveolin-1 and claudin-5 immunofluorescence within autonomic brain areas. HF-S rats versus SHAM-S exhibited reduced blood pressure, augmented vasomotor sympathetic activity, increased pressure and reduced heart rate variability, and, depressed reflex sensitivity. HF-S also presented increased caveolin-1 expression, augmented vesicle trafficking and a weak TJ (reduced TJ extension/capillary border), which determined increased BBB permeability. In contrast, exercise restored BBB permeability, reduced caveolin-1 content, normalized vesicles counting/capillary, augmented claudin-5 expression, increased TJ tightness and selectivity simultaneously with the normalization of both blood pressure and autonomic balance. Data indicate that BBB dysfunction within autonomic nuclei (increased transcytosis and weak TJ allowing entrance of plasma constituents into the brain parenchyma) underlies the autonomic imbalance in HF. Data also disclose that exercise training corrects both transcytosis and paracellular transport and improves autonomic control even in the persistence of cardiac dysfunction., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Prior expectations strongly structure the way we perceive the world and ourselves. For instance, action-outcome prediction can modulate time perception and causal experience. We designed a study that allowed us to investigate whether action-outcome prediction has similar effects on time perception and intentional causality. Participants viewed a stimulus that was consistent or inconsistent with the action they, or another agent executed. The stimulus preceded or followed these actions and participants reported simultaneity or causal judgments. Observers were more likely to report the consistent outcomes as being generated by the action, even when the outcomes actually preceded the action. However, outcome consistency did not modulate simultaneity judgments. These results shed insight on the relationship between time and causal experience. It suggests that time perception and causal experience do not rely in the same way on temporal information, the latter being more permeable to contextual cues such as action-outcome consistency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In human and non-human primates, reflexive tracking eye movements can be initiated at very short latency in response to a rapid shift of the image. Previous studies in humans have shown that only a part of the central visual field is optimal for driving ocular following responses. Herein, we have investigated spatial summation of motion information across a wide range of spatial frequencies and speeds of drifting gratings by recording short-latency ocular following responses in macaque monkeys. We show that optimal stimulus size for driving ocular responses cover a small (<20° diameter), central part of the visual field that shrinks with higher spatial frequency. This signature of linear motion integration remains invariant with speed and temporal frequency. For low and medium spatial frequencies, we found a strong suppressive influence from surround motion, evidenced by a decrease of response amplitude for stimulus sizes larger than optimal. Such suppression disappears with gratings at high frequencies. The contribution of peripheral motion was investigated by presenting grating annuli of increasing eccentricity. We observed an exponential decay of response amplitude with grating eccentricity, the decrease being faster for higher spatial frequencies. Weaker surround suppression can thus be explained by sparser eccentric inputs at high frequencies. A Difference-of-Gaussians model best renders the antagonistic contributions of peripheral and central motions. Its best-fit parameters coincide with several, well-known spatial properties of area MT neuronal populations. These results describe the mechanism by which central motion information is automatically integrated in a context-dependent manner to drive ocular responses. Significance statement Ocular following is driven by visual motion at ultra-short latency in both humans and monkeys. Its dynamics reflect the properties of low-level motion integration. Here, we show that a strong center-surround suppression mechanism modulates initial eye velocity. Its spatial properties are dependent upon visual inputs' spatial frequency but are insensitive to either its temporal frequency or speed. These properties are best described with a Difference-of-Gaussian model of spatial integration. The model parameters reflect many spatial characteristics of motion sensitive neuronal populations in monkey area MT. Our results further outline the computational properties of the behavioral receptive field underpinning automatic, context-dependent motion integration., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Barthélemy et al.)

Sensing the movement of fast objects within our visual environments is essential for controlling actions. It requires online estimation of motion direction and speed. We probed human speed representation using ocular tracking of stimuli of different statistics. First, we compared ocular responses to single drifting gratings (DGs) with a given set of spatiotemporal frequencies to broadband motion clouds (MCs) of matched mean frequencies. Motion energy distributions of gratings and clouds are point-like, and ellipses oriented along the constant speed axis, respectively. Sampling frequency space, MCs elicited stronger, less variable, and speed-tuned responses. DGs yielded weaker and more frequency-tuned responses. Second, we measured responses to patterns made of two or three components covering a range of orientations within Fourier space. Early tracking initiation of the patterns was best predicted by a linear combination of components before nonlinear interactions emerged to shape later dynamics. Inputs are supralinearly integrated along an iso-velocity line and sublinearly integrated away from it. A dynamical probabilistic model characterizes these interactions as an excitatory pooling along the iso-velocity line and inhibition along the orthogonal "scale" axis. Such crossed patterns of interaction would appropriately integrate or segment moving objects. This study supports the novel idea that speed estimation is better framed as a dynamic channel interaction organized along speed and scale axes., (Copyright © 2022 Meso et al.)

Autonomic nerves control organ function through the sympathetic and parasympathetic branches, which have opposite effects. In the bone marrow, sympathetic (adrenergic) nerves promote hematopoiesis; however, how parasympathetic (cholinergic) signals modulate hematopoiesis is unclear. Here, we show that B lymphocytes are an important source of acetylcholine, a neurotransmitter of the parasympathetic nervous system, which reduced hematopoiesis. Single-cell RNA sequencing identified nine clusters of cells that expressed the cholinergic α7 nicotinic receptor (Chrna7) in the bone marrow stem cell niche, including endothelial and mesenchymal stromal cells (MSCs). Deletion of B cell-derived acetylcholine resulted in the differential expression of various genes, including Cxcl12 in leptin receptor + (LepR + ) stromal cells. Pharmacologic inhibition of acetylcholine signaling increased the systemic supply of inflammatory myeloid cells in mice and humans with cardiovascular disease., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.Methods and Results:Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes' hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT 1 R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8 th week onwards). Marked AT 1 R protein content, myocytes's hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension., Conclusions: The close temporal relationship between changes in the LV ACE-Ang II-AT 1 R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT 1 R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase.

There is a growing interest in sex differences in human and animal cognition. However, empirical evidences supporting behavioral and neural sex differences in humans remain sparse. Visuomotor behaviors offer a robust and naturalistic empirical framework to seek for the computational mechanisms underlying sex biases in cognition. In a large group of human participants (N = 127), we investigated sex differences in a visuo-oculo-manual motor task that consists of tracking with the hand a target moving unpredictably. We report a clear male advantage in hand tracking accuracy. We tested whether men and women employ different gaze strategy or hand movement kinematics. Results show no key difference in these distinct visuomotor components. However, highly consistent differences in eye-hand coordination were evidenced by a larger temporal lag between hand motion and target motion in women. This observation echoes with other studies showing a male advantage in manual reaction time to visual stimuli. We propose that the male advantage for visuomotor tracking does not reside in a more reliable gaze strategy, or in more sophisticated hand movements, but rather in a faster decisional process linking visual information about target motion with forthcoming hand, but not eye, actions.

A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creER T2 ; Lepr fl/fl mice reveals that leptin's effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.

Innate immune cells recruited to inflammatory sites have short life spans and originate from the marrow, which is distributed throughout the long and flat bones. While bone marrow production and release of leukocyte increases after stroke, it is currently unknown whether its activity rises homogeneously throughout the entire hematopoietic system. To address this question, we employed spectrally resolved in vivo cell labeling in the murine skull and tibia. We show that in murine models of stroke and aseptic meningitis, skull bone marrow-derived neutrophils are more likely to migrate to the adjacent brain tissue than cells that reside in the tibia. Confocal microscopy of the skull-dura interface revealed myeloid cell migration through microscopic vascular channels crossing the inner skull cortex. These observations point to a direct local interaction between the brain and the skull bone marrow through the meninges.

In sensory systems, a range of computational rules are presumed to be implemented by neuronal subpopulations with different tuning functions. For instance, in primate cortical area MT, different classes of direction-selective cells have been identified and related either to motion integration, segmentation or transparency. Still, how such different tuning properties are constructed is unclear. The dominant theoretical viewpoint based on a linear-nonlinear feed-forward cascade does not account for their complex temporal dynamics and their versatility when facing different input statistics. Here, we demonstrate that a recurrent network model of visual motion processing can reconcile these different properties. Using a ring network, we show how excitatory and inhibitory interactions can implement different computational rules such as vector averaging, winner-take-all or superposition. The model also captures ordered temporal transitions between these behaviors. In particular, depending on the inhibition regime the network can switch from motion integration to segmentation, thus being able to compute either a single pattern motion or to superpose multiple inputs as in motion transparency. We thus demonstrate that recurrent architectures can adaptively give rise to different cortical computational regimes depending upon the input statistics, from sensory flow integration to segmentation.

Increasing evidence suggests that sensory stimulation not only changes the level of cortical activity with respect to baseline but also its structure. Despite having been reported in a multitude of conditions and preparations (for instance, as a quenching of intertrial variability, Churchland et al., 2010), such changes remain relatively poorly characterized. Here, we used optical imaging of voltage-sensitive dyes to explore, in V4 of an awake macaque, the spatiotemporal characteristics of both visually evoked and spontaneously ongoing neuronal activity and their difference. With respect to the spontaneous case, we detected a reduction in large-scale activity ([Formula: see text]) in the alpha range (5 to 12.5 Hz) during sensory inflow accompanied by a decrease in pairwise correlations. Moreover, the spatial patterns of correlation obtained during the different visual stimuli were on the average more similar one to another than they were to that obtained in the absence of stimulation. Finally, these observed changes in activity dynamics approached saturation already at very low stimulus contrasts, unlike the progressive, near-linear increase of the mean raw evoked responses over a wide range of contrast values, which could indicate a specific switching in the presence of a sensory inflow.

Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation., Objective: This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion., Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell activation, neutrophil accumulation, endothelial cell death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. Toll-like receptor 2 agonism activated luminal endothelial cells, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing endothelial cell injury and local thrombosis ( P <0.05)., Conclusions: These results implicate flow disturbance, neutrophils, and Toll-like receptor 2 signaling as mechanisms that contribute to superficial erosion, a cause of acute coronary syndrome of likely growing importance in the statin era., (© 2017 American Heart Association, Inc.)

Interacting with the natural environment leads to complex stimulations of our senses. Here we focus on the estimation of visual speed, a critical source of information for the survival of many animal species as they monitor moving prey or approaching dangers. In mammals, and in particular in primates, speed information is conceived to be represented by a set of channels sensitive to different spatial and temporal characteristics of the optic flow [1-5]. However, it is still largely unknown how the brain accurately infers the speed of complex natural scenes from this set of spatiotemporal channels [6-14]. As complex stimuli, we chose a set of well-controlled moving naturalistic textures called "compound motion clouds" (CMCs) [15, 16] that simultaneously activate multiple spatiotemporal channels. We found that CMC stimuli that have the same physical speed are perceived moving at different speeds depending on which channel combinations are activated. We developed a computational model demonstrating that the activity in a given channel is both boosted and weakened after a systematic pattern over neighboring channels. This pattern of interactions can be understood as a combination of two components oriented in speed (consistent with a slow-speed prior) and scale (sharpening of similar features). Interestingly, the interaction along scale implements a lateral inhibition mechanism, a canonical principle that hitherto was found to operate mainly in early sensory processing. Overall, the speed-scale normalization mechanism may reflect the natural tendency of the visual system to integrate complex inputs into one coherent percept., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Due to its inherent neural delays, the visual system has an outdated access to sensory information about the current position of moving objects. In contrast, living organisms are remarkably able to track and intercept moving objects under a large range of challenging environmental conditions. Physiological, behavioral and psychophysical evidences strongly suggest that position coding is extrapolated using an explicit and reliable representation of object's motion but it is still unclear how these two representations interact. For instance, the so-called flash-lag effect supports the idea of a differential processing of position between moving and static objects. Although elucidating such mechanisms is crucial in our understanding of the dynamics of visual processing, a theory is still missing to explain the different facets of this visual illusion. Here, we reconsider several of the key aspects of the flash-lag effect in order to explore the role of motion upon neural coding of objects' position. First, we formalize the problem using a Bayesian modeling framework which includes a graded representation of the degree of belief about visual motion. We introduce a motion-based prediction model as a candidate explanation for the perception of coherent motion. By including the knowledge of a fixed delay, we can model the dynamics of sensory information integration by extrapolating the information acquired at previous instants in time. Next, we simulate the optimal estimation of object position with and without delay compensation and compared it with human perception under a broad range of different psychophysical conditions. Our computational study suggests that the explicit, probabilistic representation of velocity information is crucial in explaining position coding, and therefore the flash-lag effect. We discuss these theoretical results in light of the putative corrective mechanisms that can be used to cancel out the detrimental effects of neural delays and illuminate the more general question of the dynamical representation at the present time of spatial information in the visual pathways., Competing Interests: The authors have declared that no competing interests exist.

It is well known that chronic hypertension is accompanied by several functional deficits in the central nervous system and peripheral tissues, most of which are corrected by exercise training. However, the biological mechanisms underlying these effects are not yet well understood. In the present chapter we summarize recent experimental evidence on cellular/molecular mechanisms supporting not only the deleterious effects of hypertension on autonomic control and peripheral circulatory deficits, but also their reversion by low to moderate aerobic exercise training. Interestingly, both hypertension and aerobic training exert their effects by acting exactly on the same pathways/mechanisms but in opposed directions.

Animals exploit antagonistic interactions for sensory processing and these can cause oscillations between competing states. Ambiguous sensory inputs yield such perceptual multistability. Despite numerous empirical studies using binocular rivalry or plaid pattern motion, the driving mechanisms behind the spontaneous transitions between alternatives remain unclear. In the current work, we used a tristable barber pole motion stimulus combining empirical and modeling approaches to elucidate the contributions of noise and adaptation to underlying competition. We first robustly characterized the coupling between perceptual reports of transitions and continuously recorded eye direction, identifying a critical window of 480 ms before button presses, within which both measures were most strongly correlated. Second, we identified a novel nonmonotonic relationship between stimulus contrast and average perceptual switching rate with an initially rising rate before a gentle reduction at higher contrasts. A neural fields model of the underlying dynamics introduced in previous theoretical work and incorporating noise and adaptation mechanisms was adapted, extended, and empirically validated. Noise and adaptation contributions were confirmed to dominate at the lower and higher contrasts, respectively. Model simulations, with two free parameters controlling adaptation dynamics and direction thresholds, captured the measured mean transition rates for participants. We verified the shift from noise-dominated toward adaptation-driven in both the eye direction distributions and intertransition duration statistics. This work combines modeling and empirical evidence to demonstrate the signal-strength-dependent interplay between noise and adaptation during tristability. We propose that the findings generalize beyond the barber pole stimulus case to ambiguous perception in continuous feature spaces.

Autism has been considered as a deficit in prediction of the upcoming event or of the sensory consequences of our own movements. To test this hypothesis, we recorded eye movements from high-functioning autistic adolescents and from age-matched controls during a blanking paradigm. In this paradigm, adolescents were instructed to follow a moving target with their eyes even during its transient disappearance. Given the absence of visual information during the blanking period, eye movements during this period are solely controlled on the basis of the prediction of the ongoing target motion. Typical markers of predictive eye movements such as the number and accuracy of predictive saccades and the predictive reacceleration before target reappearance were identical in the two populations. In addition, the synergy of predictive saccades and smooth pursuit observed during the blanking periods, which is a marker for the quality of internal models about target/eye motions, was comparable between these two populations. These results suggest that, in our large population of high-functioning autistic adolescent, both predictive abilities and internal models are left intact in Autism, at least for low-level sensorimotor transformations., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Humans are highly sensitive to symmetry. During scene exploration, the area of the retina with dense light receptor coverage acquires most information from relevant locations determined by gaze fixation. We characterized patterns of fixational eye movements made by observers staring at synthetic scenes either freely (i.e., free exploration) or during a symmetry orientation discrimination task (i.e., active exploration). Stimuli could be mirror-symmetric or not. Both free and active exploration generated more saccades parallel to the axis of symmetry than along other orientations. Most saccades were small (<2°), leaving the fovea within a 4° radius of fixation. Analysis of saccade dynamics showed that the observed parallel orientation selectivity emerged within 500 ms of stimulus onset and persisted throughout the trials under both viewing conditions. Symmetry strongly distorted existing anisotropies in gaze direction in a seemingly automatic process. We argue that this bias serves a functional role in which adjusted scene sampling enhances and maintains sustained sensitivity to local spatial correlations arising from symmetry., (Copyright © 2016 the American Physiological Society.)

We evaluated the effects of swimming training on nitric oxide (NO) modulation to glutamate microinjection within the rostral ventrolateral medulla (RVLM) in conscious freely moving rats. Male Wistar rats were submitted to exercise training (Tr) by swimming or kept sedentary (Sed) for 4 weeks. After the last training session, RVLM guide cannulas and arterial/venous catheters were chronically implanted. Arterial pressure (AP), heart rate (HR), and baroreflex control of HR (loading/unloading of baroreceptors) were recorded in conscious rats at rest. Pressor response to L-glutamate in the RVLM was compared before and after blockade of local nitric oxide (NO) production. In other Tr and Sed groups, brain was harvested for gene (qRT-PCR) and protein (immunohistochemistry) expression of NO synthase (NOS) isoforms and measurement of NO content (nitrite assay) within the RVLM. Trained rats exhibited resting bradycardia (average reduction of 9%), increased baroreflex gain (Tr: -4.41 ± 0.5 vs. Sed: -2.42 ± 0.31 b/min/mmHg), and unchanged resting MAP. The pressor response to glutamate was smaller in the Tr group (32 ± 4 vs. 53 ± 2 mmHg, p < 0.05); this difference disappeared after RVLM pretreatment with carboxy-PTIO (NO scavenger), Nw-Propyl-L-Arginine and L-NAME (NOS inhibitors). eNOS immunoreactivity observed mainly in RVLM capillaries was higher in Tr, but eNOS gene expression was reduced. nNOS gene and protein expression was slightly reduced (-29 and -9%, respectively, P > 0.05). Also, RVLM NO levels were significantly reduced in Tr (-63% vs. Sed). After microinjection of a NO-donor, the attenuated pressor response of L-glutamate in Tr group was restored. Data indicate that swimming training by decreasing RVLM NO availability and glutamatergic neurotransmission to locally administered glutamate may contribute to decreased sympathetic activity in trained subjects.

Neurons in the primary visual cortex are known for responding vigorously but with high variability to classical stimuli such as drifting bars or gratings. By contrast, natural scenes are encoded more efficiently by sparse and temporal precise spiking responses. We used a conductance-based model of the visual system in higher mammals to investigate how two specific features of the thalamo-cortical pathway, namely push-pull receptive field organization and fast synaptic depression, can contribute to this contextual reshaping of V1 responses. By comparing cortical dynamics evoked respectively by natural vs. artificial stimuli in a comprehensive parametric space analysis, we demonstrate that the reliability and sparseness of the spiking responses during natural vision is not a mere consequence of the increased bandwidth in the sensory input spectrum. Rather, it results from the combined impacts of fast synaptic depression and push-pull inhibition, the later acting for natural scenes as a form of "effective" feed-forward inhibition as demonstrated in other sensory systems. Thus, the combination of feedforward-like inhibition with fast thalamo-cortical synaptic depression by simple cells receiving a direct structured input from thalamus composes a generic computational mechanism for generating a sparse and reliable encoding of natural sensory events.

Introduction: The ability of continuous aerobic exercise training (AET) to increase baroreflex control and cardiac function in heart failure (HF) has been well described, but the comparison between continuous and interval AET on these functions is inconclusive., Objectives: To compare the effects of continuous and interval AET on cardiac function and baroreflex sensitivity (BrS) in an experimental model of HF., Methods: Rats were divided into the following groups: continuous training (HF-CT), intense interval training (HF-IIT), moderate interval training (HF-MIT), sedentary group (HF-SED), and sham sedentary (SHAM-SED). Animals underwent surgery to induce HF by ligation of the interventricular coronary artery. Six weeks after surgery, AET was started (8weeks, 3sessions/week). Echocardiography studies to assess cardiac function were performed before and after AET. At the end of the training protocols, the BrS index was assessed by stepwise intravenous infusions of sodium nitroprusside and phenylephrine., Results: All methods of exercise prevented the HF-induced increase in left ventricular diameter in diastole observed in the HF-SED rats (0.88±0.09 vs. 1.03±0.09cm; P<0.05), but only the HF-CT (28.5±6.3 vs. 39.2±12.7%; P<0.05) and HF-MIT (31.0±8.5 vs. 42.0±10.3%; P<0.05) groups exhibited an increase in ejection fraction. Nevertheless, the HF-CT group was the only group that showed a tachycardia reflex higher than that of the HF-SED group (0.87±0.34 vs. 0.20±0.05bpm/mmHg; P<0.05) and similar to that of the SHAM-SED group (1.04±0.11bpm/mmHg)., Conclusions: These results suggest that continuous and moderate interval training induced similar improvements in cardiac function but that only continuous training induced higher BrS in HF rats., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We investigated the patterns of fixational saccades in human observers performing two classical perceptual tasks: grating detection and discrimination. First, participants were asked to detect a vertical or tilted grating with one of three spatial frequencies and one of four luminance contrast levels. In the second experiment, participants had to discriminate the spatial frequency of two supra-threshold gratings. The gratings were always embedded in additive, high- or low-contrast pink noise. We observed that the patterns of fixational saccades were highly idiosyncratic among participants. Moreover, during the grating detection task, the amplitude and the number of saccades were inversely correlated with stimulus visibility. We did not find a systematic relationship between saccade parameters and grating frequency, apart from a slight decrease of saccade amplitude during grating discrimination with higher spatial frequencies. No consistent changes in the number and amplitude of fixational saccades with performance accuracy were reported. Surprisingly, during grating detection, saccade number and amplitude were similar in grating-with-noise and noise-only displays. Grating orientation did not affect substantially saccade direction in either task. The results challenge the idea that, when analyzing low-level spatial properties of visual stimuli, fixational saccades can be adapted in order to extract task-relevant information optimally. Rather, saccadic patterns seem to be overall modulated by task context, stimulus visibility and individual variability., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Exercise training (ExT) is recommended to treat hypertension along with pharmaceutical antihypertensive therapies. Effects of ExT in hypothalamic content of high mobility box 1 (HMGB1) and microglial activation remain unknown. We examined whether ExT would decrease autonomic and cardiovascular abnormalities in spontaneously hypertensive rats (SHR), and whether these effects were associated with decreased HMGB1 content, microglial activation, and inflammation in the hypothalamic paraventricular nucleus (PVN). Normotensive Wistar-Kyoto (WKY) rats and SHR underwent moderate-intensity ExT for 2 wk. After ExT, cardiovascular (heart rate and arterial pressure) and autonomic parameters (arterial pressure and heart rate variability, peripheral sympathetic activity, cardiac vagal activity, and baroreflex function) were measured in conscious and freely-moving rats through chronic arterial and venous catheterization. Cerebrospinal fluid, plasma, and brain were collected for molecular and immunohistochemistry analyses of the PVN. In addition to reduced heart rate variability, decreased vagal cardiac activity and increased mean arterial pressure, heart rate, arterial pressure variability, cardiac, and vasomotor sympathetic activity, SHR had higher HMGB1 protein expression, IκB-α phosphorylation, TNF-α and IL-6 protein expression, and microglia activation in the PVN. These changes were accompanied by higher plasma and cerebrospinal fluid levels of HMGB1. The ExT + SHR group had decreased expression of HMGB1, CXCR4, SDF-1, and phosphorylation of p42/44 and IκB-α. ExT reduced microglial activation and proinflammatory cytokines content in the PVN, and improved autonomic control as well. Data suggest that training-induced downregulation of activated HMGB1/CXCR4/microglia/proinflammatory cytokines axis in the PVN of SHR is a prompt neural adaptation to counterbalance the deleterious effects of inflammation on autonomic control., (Copyright © 2015 the American Physiological Society.)

Background & Purpose: Toll-like receptor 4 (TLR4) signaling induces tissue pro-inflammatory cytokine release and endoplasmic reticulum (ER) stress. We examined the role of TLR4 in autonomic dysfunction and the contribution of ER stress., Experimental Approach: Our study included animals divided in 6 experimental groups: rats treated with saline (i.v., 0.9%), LPS (i.v., 10mg/kg), VIPER (i.v., 0.1 mg/kg), or 4-PBA (i.p., 10 mg/kg). Two other groups were pretreated either with VIPER (TLR4 viral inhibitory peptide) LPS + VIPER (i.v., 0.1 mg/kg) or 4-Phenyl butyric acid (4-PBA) LPS + PBA (i.p., 10 mg/kg). Arterial pressure (AP) and heart rate (HR) were measured in conscious Sprague-Dawley rats. AP, HR variability, as well as baroreflex sensitivity (BrS), was determined after LPS or saline treatment for 2 hours. Immunofluorescence staining for NeuN, Ib1a, TLR4 and GRP78 in the hypothalamic paraventricular nucleus (PVN) was performed. TNF-α, TLR4 and GRP78 protein expression in the PVN were evaluated by western blot. Plasma norepinephrine levels were determined by ELISA., Key Results: Acute LPS treatment increased HR and plasma norepinephrine concentration. It also decreased HR variability and high frequency (HF) components of HR variability, as well BrS. Acute LPS treatment increased TLR4 and TNF-α protein expression in the PVN. These hemodynamic and molecular effects were partially abrogated with TLR4 blocker or ER stress inhibitor pretreatment. In addition, immunofluorescence study showed that TLR4 is co-localized with GRP78in the neurons. Further inhibition of TLR4 or ER stress was able to attenuate the LPS-induced microglia activation., Conclusions & Implications: TLR4 signaling promotes autonomic dysfunction, inflammation and microglia activation, through neuronal ER stress, in the PVN.

Multi-stable perception occurs when an image falling onto the retina has multiple incompatible interpretations. We probed this phenomenon in psychophysical experiments using a moving barber-pole visual stimulus configured as a square to generate three competing perceived directions, horizontal, diagonal and vertical. We characterised patterns in reported switching type and percept duration, classifying switches into three groups related to the direction cues driving such transitions i.e. away from diagonal, towards diagonal and between cardinals. The proportions of each class reported by participants depended on contrast. The two including diagonals dominated at low contrast and those between cardinals increased in proportion as contrast was increased. At low contrasts, the less frequent cardinals persisted for shorter than the dominant diagonals and this was reversed at higher contrasts. This observed asymmetry between the dominance of transition classes appears to be driven by different underlying dynamics between cardinal and the oblique cues and their related transitions. At trial onset we found that transitions away from diagonal dominate, a tendency which later in the trial reverses to dominance by transitions excluding the diagonal, most prominently at higher contrasts. Thus ambiguity is resolved over a contrast dependent temporal integration similar to, but lasting longer than that observed when resolving the aperture problem to estimate direction. When the diagonal direction dominates perception, evidence is found for a noisier competition seen in broader duration distributions than during dominance of cardinal perception. There remain aspects of these identified differences in cardinal and oblique dynamics to be investigated in future., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Understanding the novel signalling pathways involved in the pathogenesis of hypertension is vital for the development of effective therapeutic strategies. Recent evidence suggests a role for Toll-like receptor (TLR) 4 in the development of cardiovascular diseases. Although brain has been implicated in the pathogenesis of hypertension, the role of brain TLR4 in hypertension is largely unexplored. Therefore, we investigated the role of brain TLR4 in angiotensin (Ang) II-induced hypertension and whether central TLR4 blockade has cardioprotective effects in hypertension., Methods and Results: Hypertension was induced in male Sprague-Dawley rats by delivering AngII for 14 days. The rats were administered either specific TLR4 blocker, viral inhibitory peptide (VIPER), or control peptide, intracerebroventricularly. Blood pressure, and cardiac hypertrophy and function, was evaluated by radiotelemetry and echocardiography, respectively. Blood and paraventricular nucleus were collected for measurement of plasma norepinephrine (NE), tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and TLR4 expression, respectively. Heart was analysed for TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NFκB), and renin-angiotensin system (RAS) components. Hypertensive rats had dramatically increased TLR4 expression compared with normotensive rats. Central blockade of TLR4 delayed progression of hypertension and improved cardiac hypertrophy and function in hypertensive rats. TLR4 blockade significantly reduced myocardial TNF-α, IL-1β, iNOS levels, NFκB activity, and altered RAS components in hypertensive rats. These results were associated with reduced circulating NE levels in VIPER-treated hypertensive rats., Conclusion: These results provide mechanistic evidence that AngII-induced hypertensive effects are mediated, at least in part, by brain TLR4, and that brain TLR4 blockade attenuates AngII-induced hypertensive response, possibly via down-regulation of myocardial inflammatory molecules and sympathetic activity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Inflammation has been implicated in the pathophysiology of kidney disorders. Previous studies have documented the contributions of various inflammatory cascades in the development of kidney and other organ dysfunctions. The Toll-like receptor 4 (TLR4) inflammatory pathway is a major contributor of inflammation in the kidney. Interestingly, lipopolysaccharide (LPS), a specific ligand for TLR4, has been shown to induce acute kidney injury (AKI) in animal models. We have previously studied the beneficial effects of nonpharmacological agents, particularly blueberries (BB), in attenuating inflammation and oxidative stress. We hypothesize that BB protect against the LPS-induced AKI by inhibiting TLR4 activation and kidney injury markers. Twelve-week-old male Sprague-Dawley rats received a BB solution or saline intragastric gavage for 2 days. One group of BB and saline-gavaged animals was injected with LPS (10 mg/kg bw). Another group of rats was injected with VIPER (0.1 mg/kg iv), a TLR4-specific inhibitory peptide, 2 h before LPS administration. Compared to LPS-administered rats, the BB-pretreated animals exhibited improved glomerular filtration rate, elevated renal blood flow, and a reduced renal vascular resistance. In addition, a reduction in the rate of production of free radicals, namely total reactive oxygen species (ROS) and superoxide, was observed in the BB-supplemented LPS group. Gene and protein expressions for TLR4, proinflammatory cytokine, and acute kidney injury markers were also attenuated in animals that were pretreated with BB as measured by real time RT-PCR and Western blotting, respectively. These results in the BB-pretreated group were consistent with those in the VIPER-treated rats, and indicate that BB protects against AKI by inhibiting TLR4 and its subsequent effect on inflammatory and oxidative stress pathways., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-κB content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172±3 mmHg), pressure variability and heart rate (358±7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (-13%) at the 4th week, and, by reduced vasomotor component of pressure variability (-28%) and decreased mean arterial pressure (-7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro-inflammatory cytokines secretion within the hypothalamic paraventricular nucleus. These early adaptive responses precede the occurrence of training-induced resting bradycardia and blood pressure fall.

Perceptual multistability is a phenomenon in which alternate interpretations of a fixed stimulus are perceived intermittently. Although correlates between activity in specific cortical areas and perception have been found, the complex patterns of activity and the underlying mechanisms that gate multistable perception are little understood. Here, we present a neural field competition model in which competing states are represented in a continuous feature space. Bifurcation analysis is used to describe the different types of complex spatio-temporal dynamics produced by the model in terms of several parameters and for different inputs. The dynamics of the model was then compared to human perception investigated psychophysically during long presentations of an ambiguous, multistable motion pattern known as the barberpole illusion. In order to do this, the model is operated in a parameter range where known physiological response properties are reproduced whilst also working close to bifurcation. The model accounts for characteristic behaviour from the psychophysical experiments in terms of the type of switching observed and changes in the rate of switching with respect to contrast. In this way, the modelling study sheds light on the underlying mechanisms that drive perceptual switching in different contrast regimes. The general approach presented is applicable to a broad range of perceptual competition problems in which spatial interactions play a role.

Background: Aerobic interval exercise training has greater benefits on cardiovascular function as compared with aerobic continuous exercise training., Objective: The present study aimed at analyzing the effects of both exercise modalities on acute and subacute hemodynamic responses of healthy rats., Methods: Thirty male rats were randomly assigned into three groups as follows: continuous exercise (CE, n = 10); interval exercise (IE, n = 10); and control (C, n = 10). Both IE and CE groups performed a 30-minute exercise session. The IE group session consisted of three successive 4-minute periods at 60% of maximal velocity (Max Vel), with 4-minute recovery intervals at 40% of Max Vel. The CE group ran continuously at 50% of Max Vel. Heart rate (HR), blood pressure(BP), and rate pressure product (RPP) were measured before, during and after the exercise session., Results: The CE and IE groups showed an increase in systolic BP and RPP during exercise as compared with the baseline values. After the end of exercise, the CE group showed a lower response of systolic BP and RPP as compared with the baseline values, while the IE group showed lower systolic BP and mean BP values. However, only the IE group had a lower response of HR and RPP during recovery., Conclusion: In healthy rats, one interval exercise session, as compared with continuous exercise, induced similar hemodynamic responses during exercise. However, during recovery, the interval exercise caused greater reductions in cardiac workload than the continuous exercise.

Due to the aperture problem, the initial direction of tracking responses to a translating bar is biased towards the direction orthogonal to the bar. This observation offers a powerful way to explore the interactions between retinal and extraretinal signals in controlling our actions. We conducted two experiments to probe these interactions by briefly (200 and 400 ms) blanking the moving target (45° or 135° tilted bar) during steady state (Experiment 1) and at different moments during the early phase of pursuit (Experiment 2). In Experiment 1, we found a marginal but statistically significant directional bias on target reappearance for all subjects in at least one blank condition (200 or 400 ms). In Experiment 2, no systematic significant directional bias was observed at target reappearance after a blank. These results suggest that the weighting of retinal and extraretinal signals is dynamically modulated during the different phases of pursuit. Based on our previous theoretical work on motion integration, we propose a new closed-loop two-stage recurrent Bayesian model where retinal and extraretinal signals are dynamically weighted based on their respective reliabilities and combined to compute the visuomotor drive. With a single free parameter, the model reproduces many aspects of smooth pursuit observed across subjects during and immediately after target blanking. It provides a new theoretical framework to understand how different signals are dynamically combined based on their relative reliability to adaptively control our actions. Overall, the model and behavioral results suggest that human subjects rely more strongly on prediction during the early phase than in the steady state phase of pursuit.

During normal viewing, the continuous stream of visual input is regularly interrupted, for instance by blinks of the eye. Despite these frequents blanks (that is the transient absence of a raw sensory source), the visual system is most often able to maintain a continuous representation of motion. For instance, it maintains the movement of the eye such as to stabilize the image of an object. This ability suggests the existence of a generic neural mechanism of motion extrapolation to deal with fragmented inputs. In this paper, we have modeled how the visual system may extrapolate the trajectory of an object during a blank using motion-based prediction. This implies that using a prior on the coherency of motion, the system may integrate previous motion information even in the absence of a stimulus. In order to compare with experimental results, we simulated tracking velocity responses. We found that the response of the motion integration process to a blanked trajectory pauses at the onset of the blank, but that it quickly recovers the information on the trajectory after reappearance. This is compatible with behavioral and neural observations on motion extrapolation. To understand these mechanisms, we have recorded the response of the model to a noisy stimulus. Crucially, we found that motion-based prediction acted at the global level as a gain control mechanism and that we could switch from a smooth regime to a binary tracking behavior where the dot is tracked or lost. Our results imply that a local prior implementing motion-based prediction is sufficient to explain a large range of neural and behavioral results at a more global level. We show that the tracking behavior deteriorates for sensory noise levels higher than a certain value, where motion coherency and predictability fail to hold longer. In particular, we found that motion-based prediction leads to the emergence of a tracking behavior only when enough information from the trajectory has been accumulated. Then, during tracking, trajectory estimation is robust to blanks even in the presence of relatively high levels of noise. Moreover, we found that tracking is necessary for motion extrapolation, this calls for further experimental work exploring the role of noise in motion extrapolation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Predictive coding hypothesizes that the brain explicitly infers upcoming sensory input to establish a coherent representation of the world. Although it is becoming generally accepted, it is not clear on which level spiking neural networks may implement predictive coding and what function their connectivity may have. We present a network model of conductance-based integrate-and-fire neurons inspired by the architecture of retinotopic cortical areas that assumes predictive coding is implemented through network connectivity, namely in the connection delays and in selectiveness for the tuning properties of source and target cells. We show that the applied connection pattern leads to motion-based prediction in an experiment tracking a moving dot. In contrast to our proposed model, a network with random or isotropic connectivity fails to predict the path when the moving dot disappears. Furthermore, we show that a simple linear decoding approach is sufficient to transform neuronal spiking activity into a probabilistic estimate for reading out the target trajectory.

Moving objects generate motion information at different scales, which are processed in the visual system with a bank of spatiotemporal frequency channels. It is not known how the brain pools this information to reconstruct object speed and whether this pooling is generic or adaptive; that is, dependent on the behavioral task. We used rich textured motion stimuli of varying bandwidths to decipher how the human visual motion system computes object speed in different behavioral contexts. We found that, although a simple visuomotor behavior such as short-latency ocular following responses takes advantage of the full distribution of motion signals, perceptual speed discrimination is impaired for stimuli with large bandwidths. Such opposite dependencies can be explained by an adaptive gain control mechanism in which the divisive normalization pool is adjusted to meet the different constraints of perception and action.

In low-level sensory systems, it is still unclear how the noisy information collected locally by neurons may give rise to a coherent global percept. This is well demonstrated for the detection of motion in the aperture problem: as luminance of an elongated line is symmetrical along its axis, tangential velocity is ambiguous when measured locally. Here, we develop the hypothesis that motion-based predictive coding is sufficient to infer global motion. Our implementation is based on a context-dependent diffusion of a probabilistic representation of motion. We observe in simulations a progressive solution to the aperture problem similar to physiology and behavior. We demonstrate that this solution is the result of two underlying mechanisms. First, we demonstrate the formation of a tracking behavior favoring temporally coherent features independent of their texture. Second, we observe that incoherent features are explained away, while coherent information diffuses progressively to the global scale. Most previous models included ad hoc mechanisms such as end-stopped cells or a selection layer to track specific luminance-based features as necessary conditions to solve the aperture problem. Here, we have proved that motion-based predictive coding, as it is implemented in this functional model, is sufficient to solve the aperture problem. This solution may give insights into the role of prediction underlying a large class of sensory computations.

To efficiently drive many behaviors, sensory systems have to integrate the activity of large neuronal populations within a limited time window. These populations need to rapidly achieve a robust representation of the input image, probably through canonical computations such as divisive normalization. However, little is known about the dynamics of the corticocortical interactions implementing these rapid and robust computations. Here, we measured the real-time activity of a large neuronal population in V1 using voltage-sensitive dye imaging in behaving monkeys. We found that contrast gain of the population increases over time with a time constant of ~30 ms and propagates laterally over the cortical surface. This dynamic is well accounted for by a divisive normalization achieved through a recurrent network that transiently increases in size after response onset with a slow swelling speed of 0.007-0.014 m/s, suggesting a polysynaptic intracortical origin. In the presence of a surround, this normalization pool is gradually balanced by lateral inputs propagating from distant cortical locations. This results in a centripetal propagation of surround suppression at a speed of 0.1-0.3 m/s, congruent with horizontal intracortical axons speed. We propose that a simple generalized normalization scheme can account for both the dynamical contrast response function through recurrent polysynaptic intracortical loops and for the surround suppression through long-range monosynaptic horizontal spread. Our results demonstrate that V1 achieves a rapid and robust context-dependent input normalization through a timely push-pull between local and lateral networks. We suggest that divisive normalization, a fundamental canonical computation, should be considered as a dynamic process.

Choosing an appropriate set of stimuli is essential to characterize the response of a sensory system to a particular functional dimension, such as the eye movement following the motion of a visual scene. Here, we describe a framework to generate random texture movies with controlled information content, i.e., Motion Clouds. These stimuli are defined using a generative model that is based on controlled experimental parametrization. We show that Motion Clouds correspond to dense mixing of localized moving gratings with random positions. Their global envelope is similar to natural-like stimulation with an approximate full-field translation corresponding to a retinal slip. We describe the construction of these stimuli mathematically and propose an open-source Python-based implementation. Examples of the use of this framework are shown. We also propose extensions to other modalities such as color vision, touch, and audition.