Activity-related Signals Research Articles

PTPN3 Could Βe a Therapeutic Target of Pancreatic Cancer.

Recently, protein tyrosine phosphatase non-receptor type 3 (PTPN3) has gained attention. However, the role of PTPN3 in cancer has not been fully elucidated. In the present study, we analyzed the role of PTPN3 in pancreatic cancer and investigated whether PTPN3 could be a new therapeutic target for pancreatic cancer. Two pancreatic ductal adenocarcinoma (PDAC) cell lines were used as target cells. Cell proliferation was investigated using cell counting and a xenograft mouse model. Migration and invasion were analyzed using Transwell inserts. Activation-related signaling molecules were examined by western blotting. PTPN3 contributes to the proliferation, migration, and invasion of PDAC cells in vitro. PTPN3 promotes tumor growth in a mouse xenograft model, an action mediated partially through the MAPK pathway. PTPN3 could be a new therapeutic target for pancreatic cancer.

Advances in research on the effects of platelet activation in acute lung injury (Review).

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency or failure caused by various factors inside and outside the lungs. ALI is associated with high morbidity and a poor prognosis in hospitalized patients. The lungs serve as a reservoir for platelet precursor megakaryocytes and are closely associated with platelets. Platelets not only play a central role in hemostasis, coagulation and wound healing, but can also act as inflammatory cells capable of stimulating non-hemostatic immune functions under inflammatory conditions, participating in the progression of various inflammatory diseases, and can result in tissue damage. Therefore, it was speculated that platelets may play an important role in the pathogenesis of ALI. In this review, the latest research progress on secretion of bioactive mediators from platelets, platelet activation-related signaling pathways, and the direct contact reactions between platelets and neutrophils with endothelial cells that result in ALI are described, providing evidence to support the importance of the consideration of platelets in the search for ALI interventional targets.

The CARMENES search for exoplanets around M dwarfs

Context. Stellar activity poses one of the main obstacles for the detection and characterisation of small exoplanets around cool stars, as it can induce radial velocity (RV) signals that can hide or mimic the presence of planetary companions. Several indicators of stellar activity are routinely used to identify activity-related signals in RVs, but not all indicators trace exactly the same activity effects, nor are any of them always effective in all stars. Aims. We evaluate the performance of a set of spectroscopic activity indicators for M dwarf stars with different masses and activity levels with the aim of finding a relation between the indicators and stellar properties. Methods. In a sample of 98 M dwarfs observed with CARMENES, we analyse the temporal behaviour of RVs and nine spectroscopic activity indicators: cross-correlation function (CCF) full-width-at-half-maximum (FWHM), CCF contrast, CCF bisector inverse slope (BIS), RV chromatic index (CRX), differential line width (dLW), and indices of the chromospheric lines Hα and calcium infrared triplet. Results. A total of 56 stars of the initial sample show periodic signals related to activity in at least one of these ten parameters. RV is the parameter for which most of the targets show an activity-related signal. CRX and BIS are effective activity tracers for the most active stars in the sample, especially stars with a relatively high mass, while for less active stars, chromospheric lines perform best. FWHM and dLW show a similar behaviour in all mass and activity regimes, with the highest number of activity detections in the low-mass, high-activity regime. Most of the targets for which we cannot identify any activity-related signals are stars at the low-mass end of the sample (i.e. with the latest spectral types). These low-mass stars also show the lowest RV scatter, which indicates that ultracool M dwarfs could be better candidates for planet searches than earlier types, which show larger RV jitter. Conclusions. Our results show that the spectroscopic activity indicators analysed behave differently, depending on the mass and activity level of the target star. This underlines the importance of considering different indicators of stellar activity when studying the variability of RV measurements. Therefore, when assessing the origin of an RV signal, it is critical to take into account a large set of indicators, or at least the most effective ones considering the characteristics of the star, as failing to do so may lead to false planet claims.

Illicit Alcohol: Public Health Risk of Methanol Poisoning and Policy Mitigation Strategies.

Illicit (unrecorded) alcohol is a critical global public health issue because it is produced without regulatory and market oversight with increased risk of safety, quality and adulteration issues. Undertaking iterative research to draw together academic, contemporary and historic evidence, this paper reviews one specific toxicological issue, methanol, in order to identify the policy mitigation strategies of interest. A typology of illicit alcohol products, including legal products, illegal products and surrogate products, is created. A policy landscape matrix is produced that synthesizes the drivers of illicit alcohol production, distribution, sale and consumption, policy measures and activity related signals in order to inform policy development. The matrix illustrates the interaction between capabilities, motivations and opportunities and factors such as access, culture, community norms and behavior, economic drivers and knowledge and information and gives insight into mitigation strategies against illicit alcohol sale and consumption, which may prove of value for policymakers in various parts of the world.

Detection of Ventricular Fibrillation Based on Ballistocardiography by Constructing an Effective Feature Set.

Ventricular fibrillation (VF) is a type of fatal arrhythmia that can cause sudden death within minutes. The study of a VF detection algorithm has important clinical significance. This study aimed to develop an algorithm for the automatic detection of VF based on the acquisition of cardiac mechanical activity-related signals, namely ballistocardiography (BCG), by non-contact sensors. BCG signals, including VF, sinus rhythm, and motion artifacts, were collected through electric defibrillation experiments in pigs. Through autocorrelation and S transform, the time-frequency graph with obvious information of cardiac rhythmic activity was obtained, and a feature set of 13 elements was constructed for each 7 s segment after statistical analysis and hierarchical clustering. Then, the random forest classifier was used to classify VF and non-VF, and two paradigms of intra-patient and inter-patient were used to evaluate the performance. The results showed that the sensitivity and specificity were 0.965 and 0.958 under 10-fold cross-validation, and they were 0.947 and 0.946 under leave-one-subject-out cross-validation. In conclusion, the proposed algorithm combining feature extraction and machine learning can effectively detect VF in BCG, laying a foundation for the development of long-term self-cardiac monitoring at home and a VF real-time detection and alarm system.

Molecular subtypes based on ferroptosis-related genes and tumor microenvironment infiltration characterization in lung adenocarcinoma

ABSTRACT Recently, several molecular subtypes with different prognosis have been found in lung adenocarcinoma (LUAD). However, the characteristics of the ferroptosis molecular subtypes and the associated tumor microenvironment (TME) cell infiltration have not been fully studied in LUAD. Using 1160 lung adenocarcinoma samples, we explored the molecular subtypes mediated by ferroptosis-related genes, along with the associated TME cell infiltration. The ferroptosis score was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to quantify the ferroptosis characteristics of a single tumor. Three different molecular subtypes related to ferroptosis, with different prognoses, were identified in LUAD. Analysis of TME cell infiltration revealed immune heterogeneity among the three subtypes. Cluster A was characterized by immunosuppression and was associated with stromal activation. Cluster C was characterized by a large number of immune cells infiltrating the TME, promoting tumor immune response, and it was significantly enriched in immune activation-related signaling pathways. Relatively less infiltration of immune cells was a feature of cluster B. The ferroptosis score can predict tumor subtype, immunity and prognosis. A low ferroptosis score was characterized by immune activation and good prognosis, as seen in the cluster C subtype. Relative immunosuppression and poor prognosis were the characteristics of a high ferroptosis score, as seen in cluster A and B subtypes. At the same time, the anti-PD-1/L1 immunotherapy cohort demonstrated that a low ferroptosis score was associated with higher efficacy of immunotherapy. The ferroptosis score is a promising biomarker that could be of great significance to determine the prognosis, molecular subtypes, TME cell infiltration characteristics and immunotherapy effects in patients with LUAD.

TRPC1 Deletion Causes Striatal Neuronal Cell Apoptosis and Proteomic Alterations in Mice.

Transient receptor potential channel 1 (TRPC1) is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2′-deoxyguanosine (8-OHdG) staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased) in the stratum of TRPC1 knockout (TRPC1−/−) mice compared to that of wild type (WT) mice. Bioinformatics analysis showed these dysregulated proteins included: oxidative stress-related proteins, synaptic proteins, endoplasmic reticulum (ER) stress-related proteins and apoptosis-related proteins. STRING analysis showed these differential proteins have a well-established interaction network. Based on the proteomic data, we revealed by Western-blot analysis that TRPC1 deletion caused ER stress as evidenced by the dysregulation of GRP78 and PERK activation-related signaling pathway, and elevated oxidative stress as suggested by increased 8-OHdG staining, increased NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUV2) and decreased protein deglycase (DJ-1), two oxidative stress-related proteins. In addition, we also demonstrated that TRPC1 deletion led to significantly increased apoptosis in striatum with concurrent decrease in both 14–3–3Z and dynamin-1 (D2 dopamine (DA) receptor binding), two apoptosis-related proteins. Taken together, we concluded that TRPC1 deletion might cause striatal neuronal apoptosis by disturbing multiple biological processes (i.e., ER stress, oxidative stress and apoptosis-related signaling). These data suggest that TRPC1 may be a key player in the regulation of striatal cellular survival and death.

Bu-Shen-Tong-Luo decoction prevents bone loss via inhibition of bone resorption and enhancement of angiogenesis in ovariectomy-induced osteoporosis of rats

Ethnopharmacological relevanceGathering three ancient formulas, traditional Chinese medicine Bu-Shen-Tong-Luo decoction (BSTLD) has been used to treat postmenopausal osteoporosis (PMO) at the Jiangsu Province Hospital of Chinese Medicine for decades. However, the effect of BSTLD on angiogenesis and bone resorption as well as its possible mechanism are still unknown. Aim of the studyThis study was aimed to evaluate the preventive effect of BSTLD on ovariectomy-induced bone loss and vasculature disorder, and to investigate the possible bone protection mechanism of BSTLD in inhibiting bone resorption by enhancing angiogenesis signaling in ovariectomy-induced osteoporosis of rats. Materials and methodsThe animal experiment was divided into five groups. Rats underwent either sham surgery with intact ovaries (SHAM, n = 10) or bilateral ovariectomy (OVX, n = 40). OVX rats were randomly divided into four groups and gavaged by water (vehicle, 12 mL/kg, n = 10), BSTLD (6 g/kg, n = 10), BSTLD (12 g/kg, n = 10) and 17β-estradiol (E2, 100 μg/kg, n = 10) daily for 12 weeks, respectively. The bone loss and microstructure of the distal femur were observed using micro-computed tomography (μCT). The biomechanical parameters of the femur were detected using three-point bending tests. The distribution of osteoclasts and endothelial cells were analyzed by immunohistochemistry. The mRNA and protein levels of angiogenesis-related hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), as well as osteoclast activation-related signaling calcitonin receptor (CALCR), cathepsin K (CTSK), receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and β-catenin were assayed by RT-PCR or Western blot. ResultsBSTLD protected trabecular bone mass density and trabecular bone microstructure from ovariectomy-induced osteoporosis in rats. BSTLD significantly reduced mRNA and protein levels of calcitonin receptor and CTSK in femoral metaphysis and inhibited bone resorption in ovariectomized rats. Furthermore, BSTLD stabilized HIF-1α activity and subsequently increased VEGF expression to enhance angiogenesis and modulated RANKL/OPG signaling in this animal model. ConclusionsThese results demonstrated that BSTLD reduced osteoclasts activation and bone resorption in ovariectomy-induced osteoporosis. Bone protection by BSTLD may be associated with its stimulation of HIF-1α/VEGF angiogenesis signaling and suppression of RANKL/OPG ratio. This study may provide evidence that BSTLD treats postmenopausal osteoporosis, especially with micro-circulation complication.

The use of 1 H-NMR Metabolomics to Optimise the Extraction and Preliminary Identification of Anthelmintic Products from the Leaves of Lysiloma latisiliquum.

Tannin-rich forages are recognised as an important alternative for the control of gastrointestinal nematodes in small ruminants. Lysiloma latisiliquum, a forage commonly consumed by goats and sheep, has shown anthelmintic activity when tested against Haemonchus contortus. However, to date, the metabolites responsible for the activity are not known. To use 1 H-NMR metabolomics in the extraction and identification of anthelmintic metabolites from L. latisiliquum. Eight different solvent systems were compared for the optimum extraction of anthelmintic metabolites from L. latisiliquum. 1 H-NMR spectra of the tannin-free extracts were measured in methanol-d4 using trimethylsilylpropanoic acid (TSP) as internal standard. Extracts were also evaluated for their anthelmintic activity using the larval exsheathment inhibition assay against H. contortus. These data were correlated by multivariate analysis [principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA)] and analysed. To validate the results obtained after the OPLS-DA, a bioassay-guided isolation of bioactive metabolites was conducted. The PCA of the 1 H-NMR data allowed the identification of hydrophilic solvents as those best suited for the extraction of anthelmintics from L. latisiliquum and indicated that the bioactive metabolites are high-polarity, glycosylated products. Similarly, OPLS-DA of the data enabled the detection of activity-related signals, assigned to the glycosylated metabolites quercitrin and arbutin obtained from the bioassay-guided purification of the extract. The results of this investigation confirm metabolomics as a useful tool in the detection of bioactive metabolites in plants without previous phytochemical studies. Copyright © 2017 John Wiley & Sons, Ltd.

System Study of Vascular Smooth Muscle Cell (VSMC) Activation-Related Signaling Pathways by Monocyte and Macrophage Cells

Background: The vessel stenosis and re-stenosis processes are mainly related to cellular and molecular events. The vascular smooth muscle cell (VSMC) activation is the basic element in these lesions. Based on monocyte and macrophage inflammatory responses and also VSMC motility, a complex protein network is dynamically proposed between these cells. The aim of this study was to highlight the protein communications involved in VSMC proliferation and migration signaling pathways. Keywords: Atherosclerosis, network, cluster, pathway, VSMC, macrophage, monocyte.

Chlamydia pneumoniae Infection Promotes Vascular Smooth Muscle Cell Migration through a Toll-Like Receptor 2-Related Signaling Pathway

The migration of vascular smooth muscle cells (VSMCs) from the media to the intima is proposed to be a key event in the development of atherosclerosis. Recently, we reported that Chlamydia pneumoniae infection is involved in VSMC migration. However, the exact mechanisms for C. pneumoniae infection-induced VSMC migration are not yet well elucidated. In this study, we examined the role of the Toll-like receptor 2 (TLR2) activation-related signaling pathway in VSMC migration induced by C. pneumoniae infection. An Affymetrix-based gene expression array was conducted to identify the changes of gene expression in rat primary VSMCs (rVSMCs) infected with C. pneumoniae. Both the microarray analysis and quantitative real-time reverse transcription (RT)-PCR revealed that TLR2 mRNA expression was strongly upregulated 12 h after C. pneumoniae infection. RT-PCR and Western blot analysis further showed that the expression levels of TLR2 mRNA and protein significantly increased at the different time points after infection. Immunocytochemical analysis suggested a TLR2 recruitment to the vicinity of C. pneumoniae inclusions. Cell migration assays showed that the TLR2-neutralizing antibody could significantly inhibit C. pneumoniae infection-induced rVSMC migration. In addition, C. pneumoniae infection stimulated Akt phosphorylation at Ser 473, which was obviously suppressed by the PI3K inhibitor LY294002, thereby inhibiting rVSMC migration caused by C. pneumoniae infection. Furthermore, both the infection-induced Akt phosphorylation and rVSMC migration were suppressed by the TLR2-neutralizing antibody. Taken together, these data suggest that C. pneumoniae infection can promote VSMC migration possibly through the TLR2-related signaling pathway.

Challenges in the Development of Functional Assays of Membrane Proteins

Lipid bilayers are natural barriers of biological cells and cellular compartments. Membrane proteins integrated in biological membranes enable vital cell functions such as signal transduction and the transport of ions or small molecules. In order to determine the activity of a protein of interest at defined conditions, the membrane protein has to be integrated into artificial lipid bilayers immobilized on a surface. For the fabrication of such biosensors expertise is required in material science, surface and analytical chemistry, molecular biology and biotechnology. Specifically, techniques are needed for structuring surfaces in the micro- and nanometer scale, chemical modification and analysis, lipid bilayer formation, protein expression, purification and solubilization, and most importantly, protein integration into engineered lipid bilayers. Electrochemical and optical methods are suitable to detect membrane activity-related signals. The importance of structural knowledge to understand membrane protein function is obvious. Presently only a few structures of membrane proteins are solved at atomic resolution. Functional assays together with known structures of individual membrane proteins will contribute to a better understanding of vital biological processes occurring at biological membranes. Such assays will be utilized in the discovery of drugs, since membrane proteins are major drug targets.

Integrated MEG/fMRI Model Validated Using Real Auditory Data

The main objective of this paper is to present methods and results for the estimation of parameters of our proposed integrated magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) model. We use real auditory MEG and fMRI datasets from 7 normal subjects to estimate the parameters of the model. The MEG and fMRI data were acquired at different times, but the stimulus profile was the same for both techniques. We use independent component analysis (ICA) to extract activation-related signal from the MEG data. The stimulus-correlated ICA component is used to estimate MEG parameters of the model. The temporal and spatial information of the fMRI datasets are used to estimate fMRI parameters of the model. The estimated parameters have reasonable means and standard deviations for all subjects. Goodness of fit of the real data to our model shows the possibility of using the proposed model to simulate realistic datasets for evaluation of integrated MEG/fMRI analysis methods.

Integrated MEG and fMRI Model: Synthesis, Analysis, and Validation using Auditory Data

Event Abstract Back to Event Integrated MEG and fMRI Model: Synthesis, Analysis, and Validation using Auditory Data A. Babajani-Feremi1, J. E. Moran2 and Hamid Soltanian-Zadeh1, 3* 1 Image Analysis Lab., Radiology Department, Henry Ford Hospital, United States 2 Neuromagnetism Lab., Neurology Department, Henry Ford Hospital, United States 3 University of Tehran, Electrical and Computer Engineering Department, Iran We will present development and validation of an integrated model for magnetoencephalography (MEG) and functional Magnetic Resonance Imaging (fMRI). In the proposed model, neural activity is related to Post Synaptic Potentials (PSPs) which is the common link between MEG and fMRI. Each PSP is modeled by the direction and strength of its current flow which are treated as random variables. The overall neural activity in each voxel is used for equivalent current dipole in MEG and as input of extended Balloon model in fMRI. The model shows possibility of detecting activation by fMRI in a voxel while the voxel is silent for MEG and vice versa. Parameters of the model illustrate situations like closed field due to non-pyramidal cells, canceling effect of inhibitory PSP on excitatory PSP, and effect of synchronicity. In addition, the model shows that the crosstalk from neural activities of adjacent voxels in fMRI may result in the detection of activations in these voxels although they contain no neural activities. We use real auditory MEG and fMRI datasets from 7 normal subjects to estimate the parameters of the model. The MEG and fMRI data are acquired at different times but the stimulus profile is the same for both techniques. We use independent component analysis (ICA) to extract activation-related signal from the MEG data. The ICA component correlated with the stimulus is used to estimate the MEG parameters of the model. The temporal and spatial information of the fMRI datasets are used to estimate the fMRI parameters of the model. The parameters estimated for different subjects have reasonable means and standard deviations. Goodness of fit of the real data to the proposed model shows its ability to simulate realistic datasets for evaluation of integrated MEG and fMRI analysis methods. As such, the proposed model may play an important role in evaluating and comparing different analysis methods of MEG and fMRI. It may also be very useful in characterizing the upcoming combined methods for simultaneous analysis of MEG and fMRI. Conference: 10th International Conference on Cognitive Neuroscience, Bodrum, Turkey, 1 Sep - 5 Sep, 2008. Presentation Type: Oral Presentation Topic: Symposium 14: Multimodal Studies of Oscillations Citation: Babajani-Feremi A, Moran JE and Soltanian-Zadeh H (2008). Integrated MEG and fMRI Model: Synthesis, Analysis, and Validation using Auditory Data. Conference Abstract: 10th International Conference on Cognitive Neuroscience. doi: 10.3389/conf.neuro.09.2009.01.065 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 01 Dec 2008; Published Online: 01 Dec 2008. * Correspondence: Hamid Soltanian-Zadeh, University of Tehran, Electrical and Computer Engineering Department, Tehran, Iran, hszadeh@ut.ac.ir Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers A. Babajani-Feremi J. E Moran Hamid Soltanian-Zadeh Google A. Babajani-Feremi J. E Moran Hamid Soltanian-Zadeh Google Scholar A. Babajani-Feremi J. E Moran Hamid Soltanian-Zadeh PubMed A. Babajani-Feremi J. E Moran Hamid Soltanian-Zadeh Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Systematic investigation of balanced steady‐state free precession for functional MRI in the human visual cortex at 3 Tesla

Previous studies have applied balanced steady-state free precession (bSSFP) to functional brain imaging. Methods that exploit the strong frequency dependence of the MR signal in the bSSFP transition band are strongly affected by field inhomogeneity and frequency drifts. Recent bSSFP studies using "on-resonance" (in the bSSFP passband) acquisition claimed that higher sensitivity was achieved compared to traditional fMRI methods. However, the contrast mechanism that generates activation-related signal changes in bSSFP imaging is not yet fully understood. We performed a systematic study of on-resonance bSSFP signal behavior using a multiecho balanced SSFP sequence with different TRs at 3 Tesla. We conclude that intravoxel dephasing, or the off-resonance averaged steady state, dominates the bSSFP signal decay and determines the bSSFP fMRI contrast. Experimental findings were confirmed by simulations based on existing theories for signal formation around blood vessels in inhomogeneous tissues. The activation-induced signal change in on-resonance bSSFP increases with TE, and the TE dependence of the contrast-to-noise ratio (CNR) in bSSFP is similar to that in gradient echo-planar imaging (GE-EPI). However, GE-EPI has a significantly higher CNR efficiency.

Does Hypercapnia-Induced Cerebral Vasodilation Modulate the Hemodynamic Response to Neural Activation?

Increases in cerebral blood flow produced by vasoactive agents will increase blood oxygen level-dependent (BOLD) MRI signal intensity. The effects of such vasodilation on activation-related signal changes are incompletely characterized. The two signal changes may be simply additive or there may be more a complex interaction. To investigate this, BOLD MRI was performed in four normal male subjects using T2*-weighted echo planar imaging; brain volumes were acquired every 6.2 s, using a Siemens VISION scanner operating at 2 Tesla; each volume consisted of 64 sequential transverse slices (64 × 64 pixels per slice, 3 × 3 × 3 mm). Sixteen periods of visual stimulation were produced using a flickering checkerboard (8 Hz, 31 s On/31 s Off); this was coupled with five periods of hypercapnia (4% inspired CO2, 62 s On/124 s Off). Data were analyzed using SPM96. Mean signal intensity, calculated globally for the whole brain, closely mirrored changes in the partial pressure of end-tidal CO2 (PCO2), and hypercapnia was associated with widespread significant signal increases (P < 0.001), predominantly within grey matter. As expected, the visual stimulation produced significant signal changes within the occipital cortex (P < 0.001). Within the occipital cortex, no significant interactions (P > 0.001) between the effects of the visual stimulation and PCO2 were present. The increases in PCO2 imposed dynamically in the present study would increase cerebral blood flow by between 25 and 40%, an increase within the physiological range and comparable to that induced by neural activation. With this flow change the effects of vasodilation, on an activation-related signal change, are simply additive.

FMRI of Monkey Visual Cortex

While functional magnetic resonance imaging (fMRI) is now used widely for demonstrating neural activity-related signals associated with perceptual, motor, and cognitive processes in humans, to date this technique has not been developed for use with nonhuman primates. fMRI in monkeys offers a potentially valuable experimental approach for investigating brain function, which will complement and aid existing techniques such as electrophysiology and the behavioral analysis of the effects of brain lesions. There are, however, a number of significant technical challenges involved in using fMRI with monkeys. Here, we describe the procedures by which we have overcome these challenges to carry out successful fMRI experiments in an alert monkey, and we present the first evidence of activity-related fMRI signals from monkey cerebral cortex.

Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures

During brain development, spontaneous neuronal activity has been shown to play a crucial role in the maturation of neuronal circuitries. Activity-related signals may cause selective neuronal cell death and/or rearrangement of neuronal connectivity. To study the effects of sustained inhibitory activity on developing inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal rat telencephalon were used. In relatively immature cultures, muscimol (10 μM), a GABA A receptor agonist, induced a transient increase in apoptotic cell death, as evidenced by a cycloheximide-sensitive increase of free nucleosomes and an increased frequency of DNA double strand breaks (TUNEL labeling). Furthermore, muscimol caused an irreversible reduction of glutamic acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol-induced death of GABAergic neurons was attenuated by the GABA A receptor blockers bicuculline (100 μM) and picrotoxin (100 μM), by depolarizing potassium concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644 (2 μM). As compared to the cholinergic marker (choline acetyltransferase activity), glutamic acid decarboxylase activity was significantly more affected by various agents known to inhibit neuronal activity, including tetrodotoxin (1 μM), flunarizine (5 μM), MK 801 (50 μM) and propofol (40 μM). The present results suggest that the survival of a subpopulation of immature GABAergic neurons is dependent on sustained neuronal activity and that these neurons may undergo apoptotic cell death in response to GABA A autoreceptor activation.

Functional Magnetic Resonance Neuroimaging Data Acquisition Techniques

Functional MRI studies of human brain require rapid data acquisition techniques, to map dynamic changes with sufficient anatomical coverage. In addition, task activation studies employing functional MRI require a high scan sensitivity, in order to discriminate the small, activation-related signal changes from background noise. An overview is given of current fast scan methods, which are sensitized to detect susceptibility changes related to task-induced changes in blood oxygenation. Sources of artifacts are discussed, as well as their effect on image quality.

The astrocytic response to afferent activity blockade in chick nucleus magnocellularis is independent of synaptic activation, age, and neuronal survival

Astrocytes in nucleus magnocellularis (NM) of the chick respond to afferent activity blockade with increased immunoreactivity for glial fibrillary acidic protein (GFAP). NM neurons respond to the same manipulations with reduced protein synthesis, ribosomal dissociation, and subsequent death of a subset of these neurons. In the present study, we sought to evaluate the relationship between these neuronal and glial responses and to determine if similar activity-dependent mechanisms mediate them. We first examined the anatomical relationship between NM neurons and astrocytic processes by electron microscopy and GFAP immunostaining. Both methods showed that NM neurons deprived of activity for 6 hr were apposed by more glial processes than active NM neurons. However, we found no preferential positioning of GFAP-immunoreactive processes near neurons of the dying or surviving populations, and there were no differences in glial process apposition to dying versus surviving neurons at the EM level. To determine whether the astrocytic response is similar to the neuronal response in age dependence, GFAP immunoreactivity was analyzed in adult chickens following unilateral afferent activity blockade. Unlike the neuronal response to activity blockade, the astrocytic response is equally strong in adult animals. These results imply an independence of the neuronal and astrocytic responses to activity blockade, raising the possibility that these two cell types may be responding to different activity-related signals. This possibility was tested using an in vitro slice preparation. Unilateral stimulation of NM was provided in three ways: orthodromically, antidromically, and orthodromically in a low-calcium medium. The regulation of astrocytic GFAP immunoreactivity by these manipulations of activity was then analyzed. The results of these experiments show that, unlike neuronal protein synthesis, astrocytic GFAP immunoreactivity can be suppressed by either presynaptic or postsynaptic neuronal activity. Therefore, the astrocytes and neurons are regulated by different activity-dependent signals and, by the present measures, their responses to activity blockade appear independent of one another.