Schmittmohr7169
When listening to speech, low-frequency cortical activity tracks the speech envelope. It remains controversial, however, whether such envelope-tracking neural activity reflects entrainment of neural oscillations or superposition of transient responses evoked by sound features. Recently, it is suggested that the phase of envelope-tracking activity can potentially distinguish entrained oscillations and evoked responses. Here, we analyze the phase of envelope-tracking in humans during passive listening, and observe that the phase lag between cortical activity and speech envelope tends to change linearly across frequency in the θ band (4-8 Hz), suggesting that the θ-band envelope-tracking activity can be readily modeled by evoked responses.GABAergic somatodendritic inhibition in the preBötzinger complex (preBötC), a medullary site for the generation of inspiratory rhythm, is involved in respiratory rhythmogenesis and patterning. Nevertheless, whether GABA acts distally on presynaptic terminals, evoking presynaptic inhibition is unknown. Here, we begin to address this problem by measuring presynaptic Ca2+ transients in preBötC neurons, under rhythmic and non-rhythmic conditions, with two variants of genetically encoded Ca2+ indicators (GECIs). Organotypic slice cultures from newborn mice, containing the preBötC, were drop-transduced with jGCaMP7s, or injected with jGCaMP7f-labeling commissural preBötC neurons. Then, Ca2+ imaging combined with whole-cell patch-clamp or field stimulation was obtained from inspiratory preBötC neurons. We found that rhythmically active neurons expressed synchronized Ca2+ transients in soma, proximal and distal dendritic regions, and punctate synapse-like structures. Expansion microscopy revealed morphologic characteristics of bona fide synaptic boutons of the en passant and terminal type. Under non-rhythmic conditions, we found that bath application of the GABAA receptor agonist muscimol, and local microiontophoresis of GABA, reduced action potential (AP)-evoked and field stimulus-evoked Ca2+ transients in presynaptic terminals in inspiratory neurons and commissural neurons projecting to the contralateral preBötC. In addition, under rhythmic conditions, network rhythmic activity was suppressed by muscimol, while the GABAA receptor antagonist bicuculline completely re-activated spontaneous activity. These observations demonstrate that the preBötC includes neurons that show GABAergic inhibition of presynaptic Ca2+ transients, and presynaptic inhibition may play a role in the network activity that underlies breathing.While humans and other mammals exhibit adaptation to odorants, the neural mechanisms and brain locations involved in this process are incompletely understood. One possibility is that it primarily occurs as a result of the interactions between odorants and odorant receptors on the olfactory sensory neurons in the olfactory epithelium. In this scenario, adaptation would arise as a peripheral phenomenon transmitted to the brain. An alternative possibility is that adaptation occurs because of processing in the brain. We made an initial test of these possibilities using a two-color imaging strategy to simultaneously measure the activity of the olfactory receptor nerve terminals (input to the bulb) and mitral/tufted cell apical dendrites (output from the bulb) in anesthetized and awake mice. Repeated odor stimulation at the same concentration resulted in a decline in the bulb output, while the input remained relatively stable. Thus, the mammalian olfactory bulb appears to participate in generating the perception of outstanding question. We carried out simultaneous imaging of the input to the olfactory bulb, and the output from the bulb to the rest of the brain. This comparison revealed that the sensory input from the nose provides a relatively stable representation of the odor environment, whereas robust adaptation occurred in the bulb output. This is the second perceptual calculation, done simultaneously, by the olfactory bulb.Throughout the nervous system, the organization of excitatory and inhibitory synaptic inputs within a neuron's receptive field shapes its output computation. In some cases, multiple motifs of synaptic organization can contribute to a single computation. Here, we compare two of these mechanisms performed by two morphologically distinct retinal direction-selective ganglion cells (DSGCs) directionally tuned inhibition and spatially offset inhibition. Using drifting stimuli, we found that DSGCs that have asymmetric dendrites exhibited stronger directionally tuned inhibition than symmetric DSGCs. Using stationary stimuli to map receptive fields, we found that DSGCs with both symmetric and asymmetric dendrites exhibited similar spatially offset inhibition. Interestingly, we observed that excitatory and inhibitory synapses for both cell types were locally correlated in strength. This result indicates that in the mouse retina, dendritic morphology influences the amount of tuned inhibition attained through asymmetric wiring but does not dictate the synaptic organization of excitation relative to inhibition.In postdiction, the last stimulus of a sequence changes the perception of the preceding stimuli. Postdiction has been reported in all sensory modalities, but its neural underpinnings remain poorly understood. In the rabbit illusion, a sequence of nonequidistant stimuli presented isochronously is perceived as equidistantly spaced. This illusion might be driven by an internal prior favoring a constant-speed motion. Here, we hypothesized that prestimulus alpha oscillations (8-12 Hz), known to correlate with perceptual expectations and biases, would reflect the degree to which perceptual reports are influenced by a constant-speed prior. Human participants were presented with ambiguous visual sequences while being recorded simultaneously with MEG and EEG the same sequences yielded an illusory perception in about half the trials, allowing contrasting brain responses elicited by identical sequences causing distinct percepts. As a proxy of an individual's prior, we used the percentage of perceived illusion and the detection criterion, assuming that a strong constant-speed prior would result in a higher rate of illusory percepts. We found that high frontoparietal alpha power was associated with perceiving the sequence according to the individual's prior participants with high susceptibility to the illusion would report the illusion, while participants with low susceptibility would report the veridical sequence. Additionally, we found that prestimulus alpha phase in occipitoparietal regions dissociated illusion from no-illusion trials. We interpret our results as suggesting that alpha power reflects an individual's constant-speed prior, whereas alpha phase modulates sensory uncertainty.Full-band DC recordings enable recording of slow electrical brain signals that are severely compromised during conventional AC recordings. However, full-band DC recordings may be limited by the amplifier's dynamic input range and the loss of small amplitude high-frequency signals. Recently, Neuralynx has proposed full-band recordings with inverse filtering for signal reconstruction based on hybrid AC/DC-divider RRC filters that enable only partial suppression of DC signals. However, the quality of signal reconstruction for biological signals has not yet been assessed. Here, we propose a novel digital inverse filter based on a mathematical model describing RRC filter properties, which provides high computational accuracy and versatility. Second, we propose procedures for the evaluation of the inverse filter coefficients, adapted for each recording channel to minimize the error caused by the deviation of the real values of the RRC filter elements from their nominal values. We demonstrate that this approach enables near 99% reconstruction quality of high-potassium-induced cortical spreading depolarizations (SDs), endothelin-induced ischemic negative ultraslow potentials (NUPs), and whole-cell recordings of membrane potential using RRC filters. The quality of the reconstruction was significantly higher than with the existing inverse filtering procedures. Thus, RRC filters with inverse filtering are optimal for full-band EEG recordings in various applications.
The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood.
This community-based, case-control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006-2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 51 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression.
Compared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI 1.8 to 4.8) and 4.4 (95% CI 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI 2.1 to 50.3), 12.8 (95% CI 3.5 to 46.9) and 1.9 (95% CI 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR 5.8, 95% CI 2.2 to 15.2). Women with SSL were associated with higher risk (aOR 4.4; 95% CI 2.3 to 8.2) than men (aOR 1.7; 95% CI 0.8 to 3.8).
Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.
Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.The respiratory tract is constantly exposed to various airborne pathogens. Most vaccines against respiratory infections are designed for the parenteral routes of administration; consequently, they provide relatively minimal protection in the respiratory tract. A vaccination strategy that aims to induce the protective mucosal immune responses in the airway is urgently needed. The FcRn mediates IgG Ab transport across the epithelial cells lining the respiratory tract. E64d By mimicking this natural IgG transfer, we tested whether FcRn delivers vaccine Ags to induce a protective immunity to respiratory infections. In this study, we designed a monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain. The soluble trimeric HA-Fc were characterized by their binding with conformation-dependent HA Abs or FcRn. In wild-type, but not FcRn knockout, mice, intranasal immunization with HA-Fc plus CpG adjuvant conferred significant protection against lethal intranasal challenge with influenza A/PR/8/34 virus.