Level Of Spontaneous Activity Research Articles

Valproate-induced neurodevelopmental deficits in Xenopus laevis tadpoles.

Autism spectrum disorder (ASD) is increasingly thought to result from low-level deficits in synaptic development and neural circuit formation that cascade into more complex cognitive symptoms. However, the link between synaptic dysfunction and behavior is not well understood. By comparing the effects of abnormal circuit formation and behavioral outcomes across different species, it should be possible to pinpoint the conserved fundamental processes that result in disease. Here we use a novel model for neurodevelopmental disorders in which we expose Xenopus laevis tadpoles to valproic acid (VPA) during a critical time point in brain development at which neurogenesis and neural circuit formation required for sensory processing are occurring. VPA is a commonly prescribed antiepileptic drug with known teratogenic effects. In utero exposure to VPA in humans or rodents results in a higher incidence of ASD or ASD-like behavior later in life. We find that tadpoles exposed to VPA have abnormal sensorimotor and schooling behavior that is accompanied by hyperconnected neural networks in the optic tectum, increased excitatory and inhibitory synaptic drive, elevated levels of spontaneous synaptic activity, and decreased neuronal intrinsic excitability. Consistent with these findings, VPA-treated tadpoles also have increased seizure susceptibility and decreased acoustic startle habituation. These findings indicate that the effects of VPA are remarkably conserved across vertebrate species and that changes in neural circuitry resulting from abnormal developmental pruning can cascade into higher-level behavioral deficits.

Neuregulin 1 affects leptin levels, food intake and weight gain in normal-weight, but not obese, db/db mice

AimStudies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice. MethodsWeight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50μg/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks. ResultsLeptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment. ConclusionThe decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

Auto-inhibition at a ligand-gated ion channel: a cross-talk between orthosteric and allosteric sites.

A ligand is believed to produce either positive or negative responses, or to block both of them. However, an indole compound was found to promote both positive and negative effects at the 5-HT3 AB receptor, which displays a low level of spontaneous activity. The present study attempted to delineate the mechanisms underlying this phenomenon. The spontaneously active V291S 5-HT3 A receptor was used to explore the properties of 5-hydroxyindole (5-HoI) and 5-methoxyindole (5-MoI), structural analogues of 5-HT, either alone or in combination with orthosteric probes. Two types of efficacy switching were initiated by altering ligand structure and concentration. At lower concentrations, a subtle structural change at position 5 of the indole molecule resulted in opposite effects. 5-HoI apparently elicited partial allosteric inverse agonism, whereas 5-MoI induced allosteric agonism. Interestingly, at a higher concentration, these indoles produced distinct auto-inhibition, manifested as a switch from positive to negative effects. 5-HoI induced a transition from orthosteric agonism to allosteric inverse agonism, whereas 5-MoI produced a shift from allosteric agonism to orthosteric inverse agonism. The auto-inhibition appears to involve communication between orthosteric and allosteric sites of the active receptor conformation and/or between inactive and active conformations. An additive effect of orthosteric and allosteric inverse agonism and insensitivity of allosteric agonism to orthosteric antagonism were also demonstrated. Together, the results suggest that the moiety at position 5 of the indole structure is a critical determinant of a ligand's properties at the 5-HT3 A receptor, providing new insights into understanding ligand-receptor interactions.

Social isolation-induced increase in NMDA receptors in the hippocampus exacerbates emotional dysregulation in mice.

Epidemiological studies have shown that early life adverse events have long-term effects on the susceptibility to subsequent stress exposure in adolescence, but the precise mechanism is unclear. In the present study, mice on postnatal day 21-28 were randomly assigned to either a group or isolated cages for 8 weeks. The socially isolated (SI) mice exhibited a higher level of spontaneous locomotor activity, a longer duration of immobility in the forced swimming test (FST), significantly less prepulse inhibition (PPI) and an increase in aggressive (but not attack) behavior. However, acute stress markedly exacerbated the attack counts of the SI mice but did not affect the group housing (GH) mice. SI mice exhibited higher synaptosomal NR2A and NR2B levels in the hippocampus as compared to the GH mice. Whole-cell patch clamp recordings of CA1 neurons in hippocampal slices showed that the SI mice exhibited a higher input-output relationship of NMDAR-EPSCs as compared to the GH mice. Application of the NR2B -specific antagonist ifenprodil produced a greater attenuating effect on NMDAR-EPSCs in slices from the SI mice. NMDAR EPSCs recorded from the SI mice had a slower deactivation kinetic. MK-801, CPP and ifenprodil, the NMDA antagonists, reversed acute stress-induced exaggeration of aggressive and depressive behaviors. Furthermore, acute stress-induced exacerbation of attack behavior in the SI mice was abolished after the knockdown of NR2B expression. These results suggest that social isolation-induced increased expression of NMDA receptors in the hippocampus involves stress exacerbation of aggressive behaviors. Amelioration of aggressive behaviors by NMDA antagonists may open a new avenue for the treatment of psychopathologies that involve outbursts of emotional aggression in neglected children.

Comparative Analysis of the Effects of Blockade of Striatal Metabotropic and Ionotropic Glutamate Receptors on Motor Behavior in Rats

Chronic experiments on rats addressed the effects of blockade of NMDA and metabotropic glutamate receptors in the neostriatum on conditioned reflex avoidance (in a shuttle box) and spontaneous (in an open field) behavior. Glutamate receptor antagonists were given bilaterally into the neostriatum, in some experiments with the GABAA receptor antagonist picrotoxin (2 μg), which impairs execution of conditioned reflex skills and produces choreomyoclonic hyperkinesia. The most effective agent in preventing the adverse effects of picrotoxin on behavior was the type 5 metabotropic receptor antagonist MTEP (3 μg), which when given into the neostriatum without picrotoxin had no effect on measures of avoidance behavior and did not alter the level of spontaneous motor activity. In contrast, the type 1 metabotropic receptor antagonist EMQMCM (3 μg) degraded measures of normal motor behavior (indicative of a sedative effect) but did not prevent the actions of picrotoxin. The NMDA receptor antagonist MK-801 (dizocilpine, 1 and 5 μg) decreased picrotoxin-induced hyperkinesia but had only mild effects on its adverse influence on conditioned reflex activity; given alone into the striatum, it decreased normal motor activity. Considering the distributions of the study receptors on neostriatal neuron membranes, it is suggested that the most effective action, on type 5 glutamate receptors, may be linked with their involvement in supporting the activity of the “indirect” efferent pathway, the activity of which is impaired in the hyperkinetic type of dysfunction of the extrapyramidal motor system in Huntington’s chorea in humans.

Emergence of Context-Dependent Variability across a Basal Ganglia Network

Context dependence is a key feature of cortical-basal ganglia circuit activity, and in songbirds the cortical outflow of a basal ganglia circuit specialized for song, LMAN, shows striking increases in trial-by-trial variability and bursting when birds sing alone rather than to females. To reveal where this variability and its social regulation emerge, we recorded stepwise from corticostriatal (HVC) neurons and their target spiny and pallidal neurons in Area X. We find that corticostriatal and spiny neurons both show precise singing-related firing across both social settings. Pallidal neurons, in contrast, exhibit markedly increased trial-by-trial variation when birds sing alone, created by highly variable pauses in firing. This variability persists even when recurrent inputs from LMAN are ablated. These data indicate that variability and its context sensitivity emerge within the basal ganglia network, suggest a network mechanism for this emergence, and highlight variability generation and regulation as basal ganglia functions.

Functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection in rats

Spinal cord injury may produce long-term reorganization of cortical circuits. Little is known, however, about the early neurophysiological changes occurring immediately after injury. On the one hand, complete thoracic spinal cord transection of the spinal cord immediately decreases the level of cortical spontaneous activity and increases the cortical responses to stimuli delivered to the forepaw, above the level of the lesion. On the other hand, a thoracic spinal cord hemisection produces an immediate cortical hyperexcitability in response to preserved spinothalamic inputs from stimuli delivered to the hindpaw, below the level of the lesion. Here we show that a thoracic spinal cord hemisection also produces a bilateral increase of the responses evoked in the forepaw cortex by forepaw stimuli, associated with a bilateral decrease of cortical spontaneous activity. Importantly, the increased cortical forepaw responses are immediate in the cortex contralateral to the hemisection (significant within 30min after injury), but they are progressive in the cortex ipsilateral to the hemisection (reaching significance only 2.5h after injury). Conversely, the decreased cortical spontaneous activity is progressive both ipsilaterally and contralaterally to the hemisection (again reaching significance only 2.5h after injury). In synthesis, the present work reports a functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection, which is likely important to fully understand the mechanisms underlying long-term cortical reorganization after incomplete spinal cord injuries.

Inhibition of striatal‐enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption

The STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61 ) inhibits the activity of the tyrosine kinase Fyn and dephosphorylates the GluN2B subunit of the NMDA receptor, whereas the protein kinase A phosphorylation of STEP61 inhibits the activity of the phosphatase (Pharmacol. Rev., 64, , p. 65). Previously, we found that ethanol activates Fyn in the dorsomedial striatum (DMS) leading to GluN2B phosphorylation, which, in turn, underlies the development of ethanol intake (J. Neurosci., 30, , p. 10187). Here, we tested the hypothesis that inhibition of STEP61 by ethanol is upstream of Fyn/GluN2B. We show that exposure of mice to ethanol increased STEP61 phosphorylation in the DMS, which was maintained after withdrawal and was not observed in other striatal regions. Specific knockdown of STEP61 in the DMS of mice enhanced ethanol-mediated Fyn activation and GluN2B phosphorylation, and increased ethanol intake without altering the level of water, saccharine, quinine consumption or spontaneous locomotor activity. Together, our data suggest that blockade of STEP61 activity in response to ethanol is sufficient for the activation of the Fyn/GluN2B pathway in the DMS. Being upstream of Fyn and GluN2B, inactive STEP61 in the DMS primes the induction of ethanol intake. We show that ethanol-mediated inhibition of STEP61 in the DMS leads to Fyn activation and GluN2B phosphorylation. (a) Under basal conditions, active STEP61 inhibits Fyn activity and dephosphorylates GluN2B. (b) Ethanol leads to the phosphorylation of STEP61 on a specific inhibitory site. The inhibition of STEP61 activity contributes to the activation of Fyn in response to ethanol, which, in turn, phosphorylates GluN2B. These molecular adaptations in the DMS promote ethanol drinking.

The health impact of sedentary behaviour in children and youth

Emerging evidence suggests that sedentary behaviour is independently associated with cardiometabolic disease risk in school-aged children and youth. This thesis includes 4 related studies in the pursuit of 2 objectives: (i) To determine the cross-sectional association of sedentary time, interruptions in sedentary time, sedentary bout length, and total movement variability with markers of cardiometabolic disease risk among children and youth; and (ii) to examine the impact of 1-day of prolonged sedentary behaviour, with and without interruptions or structured physical activity, on markers of cardiometabolic disease risk, hunger, food intake and spontaneous physical activity levels in children and youth. In Study 1, we found that interruptions in sedentary time and short bouts of sedentary time were beneficially associated with clustered cardiometabolic disease risk in boys and girls aged 8–11 years, independent of total sedentary time, moderate-and-vigorous physical activity (MVPA), and other confounders (all p < 0.05), while the opposite was true for screen-based sedentary behaviours. In Study 2, we found that movement variability (minute-to-minute changes in movement intensity) was negatively associated with clustered cardiometabolic disease risk and systolic blood pressure independent of MVPA, sedentary time and other covariates in a representative sample of American children and youth aged 12–17 years (all p < 0.05). In Studies 3 and 4, we found that prolonged sitting, with or without interruptions and structured MVPA, did not result in acute changes in markers of cardiometabolic disease risk or subsequent ad libitum food intake or physical activity levels in healthy children aged 10–14 years (all p ≥ 0.05). Taken together, the studies that make up this thesis suggest that optimal levels of cardiometabolic disease risk are most likely to be seen in children who limit their time engaging in screen-based sedentary behaviours, who frequently interrupt their sedentary time, and who have high levels of variability in their movement behaviours.

The Health Impact of Sedentary Behaviour In Children and Youth

Emerging evidence suggests that sedentary behaviour is independently associated with cardiometabolic disease risk in school-aged children and youth. This thesis includes 4 related studies in the pursuit of 2 objectives: (i) To determine the cross-sectional association of sedentary time, interruptions in sedentary time, sedentary bout length, and total movement variability with markers of cardiometabolic disease risk among children and youth; and (ii) to examine the impact of 1-day of prolonged sedentary behaviour, with and without interruptions or structured physical activity, on markers of cardiometabolic disease risk, hunger, food intake and spontaneous physical activity levels in children and youth. In Study 1, we found that interruptions in sedentary time and short bouts of sedentary time were beneficially associated with clustered cardiometabolic disease risk in boys and girls aged 8–11 years, independent of total sedentary time, moderate-and-vigorous physical activity (MVPA), and other confounders (...

Hyperactivity and alterations in iron homeostasis in mu opioid receptor knockout mice: possible implications for restless legs syndrome/Willis-Ekbom disease

Introduction Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a neurological disorder that is manifested generally at rest by an urge to move and is often accompanied by unpleasant sensations in the legs. Studies have demonstrated that the degree of opioid receptor binding is inversely proportional to the severity of RLS symptoms and there is a decrease in thalamic beta-endorphin and met- enkephalin, which are endogenous opioid peptides, in RLS patients. Furthermore, μ - opioid receptor agonists have been used to treat RLS patients. In this study we examined the relevance of the mu opioid receptor to RLS. Materials and methods To test the hypothesis that the μ -opioid receptor plays a role in RLS pathophysiology we have taken advantage of a previously generated μ -opioid receptor knockout (KO) mouse. We analyzed the KO mice for RLS-like phenotypes, including spontaneous activity levels, voluntary wheel running levels during the day and night, and sleep structure. Additionally, we measured the levels of neurotransmitters and their metabolites in the striatum using high performance liquid chromatography. Lastly, we examined the KO mice and mice treated with a potent irreversible antagonist for the μ -opioid receptor for alterations in iron homeostasis in the brain, liver, spleen, and serum using atomic absorption spectroscopy, colorimetric assays, and Western blot analysis. Results We have found that mice deficient for the μ -opioid receptor have increased wheel running activity during the rest phase, parallel to human RLS. Furthermore, we have found that loss of the μ -opioid receptor or pharmacological blockade of the mu opioid receptor using an antagonist leads to alterations in iron homeostasis in the periphery, in particular in the serum and spleen. However, we did not observe any alterations in the dopaminergic, serotonergic, or iron systems in the striatum of the μ -opioid receptor KO mice. Conclusion Taken together, while the μ -opioid receptor knockout mice do not match human RLS perfectly, they do have sleep period hyperactivity as expected of an animal model of RLS. Furthermore, the data suggest an interesting role of the mu opioid receptor in iron homeostasis that will need to be investigated in detail in future studies. Acknowledgements We thank Chad C. Cheetham, Atbin Doroodchi, Miki Jinno, Ning Peng, and J. Michael Wyss for their technical assistance and stimulating discussions. This work was supported by the National Institutes of Health (grants NS37409, NS47466, NS47692, NS54246, NS57098, NS65273, NS72872 and NS74423) and startup funds from the Departments of Neurology at UAB and UF.

Mechanisms underlying obesity resistance associated with high spontaneous physical activity

Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXRs) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the OX1R and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity-resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in obesity-resistant rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in the mediation of SPA and running wheel activity.

Children and youth do not compensate for an imposed bout of prolonged sitting by reducing subsequent food intake or increasing physical activity levels: a randomised cross-over study

The behavioural impact of an imposed bout of prolonged sitting is yet to be investigated in the paediatric population. The objective of the present study was to determine the acute effect of prolonged sitting on ad libitum food intake and spontaneous physical activity (PA) levels in healthy children and youth. A total of twenty healthy youth (twelve males and eight females) aged 10-14 years, with a mean BMI of 18·6 (sd 4·3) kg/m², were exposed to three experimental conditions in a random order: (1) a day of uninterrupted sitting (Sedentary); (2) a day of sitting interrupted with a 2 min light-intensity walk break every 20 min (Breaks); (3) a day of sitting interrupted with a 2 min light-intensity walk break every 20 min as well as 2 × 20 min of moderate-intensity PA (Breaks+PA). Food intake (ad libitum buffet meal) and PA (accelerometry for 24 h) were assessed following exposure to each experimental condition. Despite significant differences in sedentary behaviour and activity levels during the three in-laboratory sessions (all P< 0·01), we did not observe any differences in ad libitum food intake immediately following exposure to each experimental condition or any changes in the levels of sedentary behaviour or PA in the 24 h following exposure to each experimental condition (all P>0·25). These findings suggest that children and youth may not compensate for an imposed bout of sedentary behaviour by reducing subsequent food intake or increasing PA levels.

An Optimal Power-Law for Synchrony and Lognormally Synaptic Weighted Hub Networks

Details about the structure of a network model are revealed at the spontaneous spike activity level, in which the power-law of synchrony is optimized to that observed in the CA3 hippocampal slice cultures. The network model is subject to spike noise with exponentially distributed interspike intervals. The excitatory (E) and/or inhibitory (I) neurons interact through synapses whose weights show a log-normal distribution. The spike behavior observed in the network model with the appropriate log-normal distributed synaptic weights fits best to that observed in the experiment. The best-fit is then achieved with high activities of I neurons having a hub-like structure, in which the I neurons, subject to optimized spike noise, are intensively projected from low active E neurons.

Positive effect of the use of accelerometry on lifestyle awareness of overweight hypertensive patients.

Sedentary habits are strongly associated with increase of cardiovascular risk factors. The present study aimed to verify the role of accelerometry in identifying sedentary behavior, and the possible short term positive effect of this intervention on some anthropometric variables in a group of patients with cardiovascular risks factors. To quantify daily Spontaneous Motor Activity (SMA) levels and identify sedentary behavior, an accelerometer was employed, in addition to a simple questionnaire, in a group of overweight, hypertensive subjects. A personalized unsupervised 3 month long physical exercise program was planned. After this time, acceleroometry was again undertaken to analyze the impact of the intervention on some life style parameters, including the number of the steps taken daily, and Physical Activity Level (PAL). In addition, body water balance, weight, and Body Mass Index (BMI) were also evaluated. Assessment of physical activity by accelerometry identifies sedentary behaviors in a larger number of individuals. After three months of regular unsupervised aerobic exercise, PAL improved from 1.56 ±0.1 to 1.68±0.2 with P<0.005, weight (kg) reduced from 85.13 ± 20 to 83.10 ± 19 (P<0.05), BMI from 29.58 to 28.7 (P<0.05). Accelerometry allows to objectify PAL, and can be used to monitor improvement of variables strongly related to cardiovascular risk.

GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzed Cebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

Spontaneous Calcium Transients in Human Neural Progenitor Cells Mediated by Transient Receptor Potential Channels

Calcium signals affect many developmental processes, including proliferation, migration, survival, and apoptosis, processes that are of particular importance in stem cells intended for cell replacement therapies. The mechanisms underlying Ca(2+) signals, therefore, have a role in determining how stem cells respond to their environment, and how these responses might be controlled in vitro. In this study, we examined the spontaneous Ca(2+) activity in human neural progenitor cells during proliferation and differentiation. Pharmacological characterization indicates that in proliferating cells, most activity is the result of transient receptor potential (TRP) channels that are sensitive to Gd(3+) and La(3+), with the more subtype selective antagonist Ruthenium red also reducing activity, suggesting the involvement of transient receptor potential vanilloid (TRPV) channels. In differentiating cells, Gd(3+) and La(3+)-sensitive TRP channels also appear to underlie the spontaneous activity; however, no sub-type-specific antagonists had any effect. Protein levels of TRPV2 and TRPV3 decreased in differentiated cells, which is demonstrated by western blot. Thus, it appears that TRP channels represent the main route of Ca(2+) entry in human neural progenitor cells (hNPCs), but the responsible channel types are subject to substitution under differentiating conditions. The level of spontaneous activity could be increased and decreased by lowering and raising the extracellular K(+) concentration. Proliferating cells in low K(+) slowed the cell cycle, with a disproportionate increased percentage of cells in G1 phase and a reduction in S phase. Taken together, these results suggest a link between external K(+) concentration, spontaneous Ca(2+) transients, and cell cycle distribution, which is able to influence the fate of stem and progenitor cells.

Expression of c‐fos in hilar mossy cells of the dentate gyrus in vivo

Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. Therefore, adult male rats were perfused shortly after removal from their home cage and transfer to the laboratory. Remarkably, most c-fos immunoreactivity (ir) was in the hilus, especially temporal hippocampus. C-fos-ir hilar cells co-expressed GluR2/3, suggesting that they were MCs. C-fos-ir MCs were robust even when the animal was habituated to the investigator and laboratory where they were euthanized. However, c-fos-ir in dorsal MCs was reduced under these circumstances, suggesting that ventral and dorsal MCs are functionally distinct. Interestingly, there was an inverse relationship between MC and GC layer c-fos expression, with little c-fos expression in the GC layer in ventral sections where MC expression was strong, and the opposite in dorsal hippocampus. The results support the hypothesis that a subset of hilar MCs are spontaneously active in vivo and provide other DG neurons with tonic depolarizing input.

Influence of photoperiod in exercise performance and central nervous system activation

AimsIn the present study, we sought to investigate the relationship between photoperiodic daily fluctuations of internal body temperature (Tcore) with physical capacity (Workload) and neuronal activation induced by progressive treadmill exercise test.MethodsAnimals were subjected to protocols of progressive exercise test (n=11), resting on treadmill (n=12) or without prior manipulation (n=12) during dark and light phases. At the end of the last experimental session, the animals were perfused and the brains removed for immunohistchemical analysis of neuronal activation in the locus coeruleus (LC), paraventricular nucleus (PVN), supra‐optic nucleus (SO) and suprachiasmatic nucleus (SQN).ResultsWorkload was 23% higher in the light phase when compared to dark phase exercise (p&lt;0.001). PVN, SO and LC were strongly activated by exercise until fatigue independent of circadian phase (p&lt;0.001). The SQN was not activated neither by exercise nor time of the day. A strong correlation between the activation of PVN, SO and LC was found only during the dark phase of the photoperiod.ConclusionThereafter, the time of the day, possibly through its centrally mediated mechanisms favors physical performance during light phase independent of basal spontaneous locomotor activity levels. Besides, the SQN seemed to be resistant to exercise related disturbances.Research sponsored by CAPES, CNPq and FAPEMIG.

Alzheimer's disease-related changes in regional spontaneous brain activity levels and inter-region interactions in the default mode network

The degree of Granger causal modeling estimated influence for a brain region was reported to predict its blood oxygenation level-dependent (BOLD) activity level in the resting-state default mode network (DMN). Many brain disorders, such as Alzheimer's disease (AD), may alter the influence strength, activity levels, or both. Whether the relationship or prediction between these two will be affected under disease condition is unknown. In this study, the spontaneous brain activity, and inter-regional Granger causality connection were investigated over eight core DMN regions in AD patients in contrast to that in normal controls. Compared to normal control (NC), AD patients had both decreased BOLD activity level and Granger causal influence in medial prefrontal cortex and decreased activity level in inferior parietal cortex showed. However, the positive correlation between the BOLD activity level and the degree of the Granger causal modeling defined influence was found not altered by AD.