8,953 research outputs found

    Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans

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    In the present study, we investigated changes in regional cerebral blood flow (rCBF) in humans during the progression from relaxed wakefulness through slow wave sleep (SWS). These changes were examined as a function of spindle (12-15 Hz) and delta (1.5-4.0 Hz) electroencephalographic (EEG) activity of SWS. rCBF was studied with positron emission tomography (PET) using the H215O bolus method. A maximum of six 60 sec scans were performed per subject during periods of wakefulness and stages 1-4 of SWS, as determined by on-line EEG monitoring. Spectral analysis was performed off-line on the EEG epochs corresponding to the scans for computation of activity in specific frequency bands. The relationship between EEG frequency band activity and normalized rCBF was determined by means of a voxel-by-voxel analysis of covariance. delta activity covaried negatively with rCBF most markedly in the thalamus and also in the brainstem reticular formation, cerebellum, anterior cingulate, and orbitofrontal cortex. After the effect of delta was removed, a significant negative covariation between spindle activity and the residual rCBF was evident in the medial thalamus. These negative covariations may reflect the disfacilitation and active inhibition of thalamocortical relay neurons in association with delta and spindles, as well as the neural substrates underlying the progressive attenuation of sensory awareness, motor responsiveness, and arousal that occur during SWS. delta activity covaried positively with rCBF in the visual and auditory cortex, possibly reflecting processes of dream-like mentation purported to occur during SW

    TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

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    The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCĪ²3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCĪ²3 and the TRPV1 channel; 2) serotonin, or a selective agonist, Ī±-methyl-serotonin (Ī±-Me-5-HT), requires the presence of PLCĪ²3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCĪ²3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD^+ neurons that represent ā‰ˆ90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1+ nociceptors led to a significant behavioral deficit for pruritogens, including Ī±-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways

    High affinity germinal center B cells are actively selected into the plasma cell compartment

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    A hallmark of T cellā€“dependent immune responses is the progressive increase in the ability of serum antibodies to bind antigen and provide immune protection. Affinity maturation of the antibody response is thought to be connected with the preferential survival of germinal centre (GC) B cells that have acquired increased affinity for antigen via somatic hypermutation of their immunoglobulin genes. However, the mechanisms that drive affinity maturation remain obscure because of the difficulty in tracking the affinity-based selection of GC B cells and their differentiation into plasma cells. We describe a powerful new model that allows these processes to be followed as they occur in vivo. In contrast to evidence from in vitro systems, responding GC B cells do not undergo plasma cell differentiation stochastically. Rather, only GC B cells that have acquired high affinity for the immunizing antigen form plasma cells. Affinity maturation is therefore driven by a tightly controlled mechanism that ensures only antibodies with the greatest possibility of neutralizing foreign antigen are produced. Because the body can sustain only limited numbers of plasma cells, this ā€œquality controlā€ over plasma cell differentiation is likely critical for establishing effective humoral immunity
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