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Biomedical subjects

S L Bressler

Publications and source records attributed to S L Bressler.

14 recordsLinked to original sources

Mapping and expression of the ubiquitin-activating enzyme E1 (Ube1) gene in the mouse.

The nucleotide sequence of the human cDNA encoding ubiquitin-activating enzyme E1 is more than 99% identical with the human A1S9T cDNA, a gene that has been shown to complement the temperature-sensitive mutant mouse cell line, tsA1S9. The amino acid sequences of the proteins encoded by these two cDNA sequences are identical, and both cDNAs were previously shown to be located in the same region of the human X chromosome; thus, ubiquitin-activating enzyme E1 and A1S9T appear to be the same gene, designated UBE1. By in situ hybridization to metaphase chromosomes from male mice and by Southern blot analysis of male and female mouse DNA, we show that, in the mouse, a human UBE1 cDNA probe identified both X- and Y-linked loci. Ube1 is located at band A2 of the mouse X Chromosome (Chr) and Ube2 on the short arm of the Y Chr. This is in contrast to the situation in the human, where there is no evidence for Y-linked sequences related to UBE1. Mapping of the Ube1 gene in interspecific backcrosses between Mus spretus and C57BL/6 shows that the Ube1 locus maps close to Timp, in a conserved region of the mouse and human X Chrs that include Otc, Cybb, Syn1, Timp, and Araf. Expression of Ube1 on the inactive X Chr was examined to determine whether this gene is subject to X-Chr inactivation in the mouse, as there is previous evidence that the human UBE1 gene escapes, at least partially, X inactivation. Sequencing of reverse transcriptase polymerase chain reaction (RT-PCR) products from M. spretus, C57BL/6J, and T(X;16)16H x M. spretus F1 female mice indicates that the mouse Ube1 gene is subject to X-Chr inactivation in vivo. This represents a new example of differences between the sex chromosomes of mouse and human.

Animals

Inactivation of the Zfx gene on the mouse X chromosome.

ZFX, an X chromosome-linked gene encoding a zinc-finger protein, has previously been shown to escape X inactivation in humans. Here we report studies of the inactivation status of the homolog, Zfx, on the mouse X chromosome. We took advantage of both the preferential inactivation of the normal X chromosome in females carrying the T(X;16)16H translocation and the high degree of nucleotide sequence variation between the laboratory strain of mouse [corrected] and Mus spretus genomes. An EcoRV restriction fragment difference between laboratory strain of mouse [corrected] and M. spretus was detected after amplification of Zfx transcripts using the reverse transcription-polymerase chain reaction. Using this allelic variation, we assessed expression of the two Zfx genes in females carrying the T(X;16)16H translocation (from laboratory strain of mouse [corrected]) and an intact X chromosome (from M. spretus). Such females exhibit Zfx transcription from the active laboratory strain of mouse [corrected] chromosome but not from the inactive M. spretus chromosome. These results indicate that the mouse Zfx gene is subject to X inactivation.

Animals

Inactivation of the Rps4 gene on the mouse X chromosome.

The human RPS4X and RPS4Y genes, located on the X and Y chromosomes, appear to encode isoforms of ribosomal protein S4. Haploinsufficiency of these genes may contribute to the human phenotype known as Turner syndrome. Although RPS4X maps near the X-inactivation center, the gene is expressed on inactive human X chromosomes. We cloned Rps4, the mouse homolog of RPS4X. Exploiting allelic variation in Rps4, we examined transcription of the gene from active and inactive mouse X chromosomes in vivo, in female mice carrying an X-autosome translocation. We report that mouse Rps4, unlike human RPS4X, is subject to X inactivation. This finding may explain, at least in part, why the phenotypic consequences of X monosomy are less severe in mice than in humans.

Alleles

Effects of prolonged mental work on functional brain topography.

Topographic patterns of event-related covariance between electrodes were measured from subjects performing a difficult memory and fine-motor control task for 10-14 h. Striking changes occurred in the patterns after subjects performed the task for an average of 7-9 h, but before performance deteriorated. Pattern strength was reduced in a fraction-of-a-second-long response preparation interval over midline precentral areas and over the entire left hemisphere. By contrast, pattern strength in a succeeding response inhibition interval was reduced over all areas. The pattern changed least in an intervening interval associated with visual-stimulus processing. This suggests that, in addition to the well-known global reduction in neuroelectric signal strength, functional neural networks are selectively affected by sustained mental work in specific fraction-of-a-second task intervals.

Analysis of Variance

Changes in electrical activity of rabbit olfactory bulb and cortex to conditioned odor stimulation.

Rabbits with chronically implanted electrodes in olfactory bulb and cortex were classically conditioned to give an increase in relative frequency of sniffing to odor stimuli (CS+) reinforced with mild electric shock. Electroencephalographic high-frequency (35-85 Hz) bursts were recorded from an ensemble of nine bulbar depth electrodes and a second ensemble of 50 cortical surface electrodes. The olfactory cortex responded to the CS+ with sustained elevation of burst amplitude even though the olfactory bulb, from which it receives its primary centripetal input, underwent a marked decline in burst amplitude during the same time period. The amplitude reduction was not spatially uniform: The burst of the bulbar region that declined most in amplitude had the greatest phase lag with respect to the bulbar ensemble average burst. These effects were learning related because they did not occur for CS+ trials at the beginning of conditioning or for unreinforced control trials at any time.

Action Potentials

Relation of olfactory bulb and cortex. I. Spatial variation of bulbocortical interdependence.

Traces of extracellular electrical activity were simultaneously recorded from multiple electrode sites of the olfactory bulb and cortex of 10 alert, minimally restrained rabbits. Rhythmic bursts of 35-85 cps activity appeared concurrently in both structures on the inspiratory phase of a respiratory slow wave. Bulbocortical correlation was significantly higher during bursts than during interburst segments. Four conditions were expected to indicate interdependence of a bulbar and a cortical recording site: (1) a common bulbar and cortical burst frequency; (2) high bulbocortical burst correlation; (3) low bulbocortical burst phase dispersion; and (4) correlation between bulbar and cortical burst amplitudes. Pairs of sites were found which satisfied all 4 conditions. Mean bulbocortical correlation was inversely related to phase dispersion over all the site pairs examined. Significant variation in both correlation and phase dispersion was found with location of the recording sites in the bulb and in the cortex. Sites in the olfactory bulb thus differed significantly in their relation with cortical sites, and likewise, cortical sites differed significantly in their relation with bulbar sites. It is concluded that interdependence between the olfactory bulb and cortex can be detected in the relation of their field potentials and that the interdependence is spatially non-uniform.

Animals

Relation of olfactory bulb and cortex. II. Model for driving of cortex by bulb.

The major projection pathway of the olfactory bulb is by way of the lateral olfactory tract (LOT) to the olfactory cortex. Oscillatory bursts of extracellular potential appear during inspiration in both bulb and cortex. Based on anatomical and physiological considerations, a model was proposed, consisting of a bulbar transmitter, a conduction line representing axons in the LOT, and a cortical receiver. The model predicted the relation between phase and frequency of bulbar and cortical burst pairs, based on the expectation that the bulb drives the cortex. Experimental phase-frequency plots were computed from bursts of 9 bulbocortical electrode site pairs from each of 10 rabbits. For each site pair, the model predicted the expected range of the joint variation of phase and frequency, using the known distance between the bulbar and cortical sites. The model was highly successful (greater than 95% prediction accuracy) for one quarter of the total number of site pairs examined. The wide range of variation for the rest of the data suggested that higher order interactions are responsible for the phase relation between bulb and cortex. Convergence of input, independence of the cortical generator, cortical feedback to the bulb and synchronization by an outside source are all discussed as possible contributors to this variation.

Animals

Human neuroelectric patterns predict performance accuracy.

In seven right-handed adults, the brain electrical patterns before accurate performance differed from the patterns before inaccurate performance. Activity overlying the left frontal cortex and the motor and parietal cortices contralateral to the performing hand preceded accurate left- or right-hand performance. Additional strong activity overlying midline motor and premotor cortices preceded left-hand performance. These measurements suggest that brief, spatially distributed neural activity patterns, or "preparatory sets," in distinct cognitive, somesthetic-motor, and integrative motor areas of the human brain may be essential precursors of accurate visuomotor performance.

Adult

Improved event-related potential estimation using statistical pattern classification.

A new method of ERP estimation with minimal statistical assumptions is presented. A mathematical pattern classification procedure is used to select trials with discriminable event-related signals in a time interval of interest. A method of forming a reference 'baseline' is also presented. Stimulus-registered and response-registered 'enhanced' ERP averages computed from selected trials of a visuo-motor experiment show substantial enhancement of event-related signals, especially for channels with weak signals, while rejected trials have minimal event-related signals.

Adult

Event-related covariances during a bimanual visuomotor task. II. Preparation and feedback.

Event-related covariance (ERC) patterns were computed from pre-stimulus and feedback intervals of a bimanual, visuomotor judgment task performed by 7 right-handed men. Late contingent negative variation (CNV) ERC patterns that preceded subsequently accurate right- or left-hand responses differed from patterns that preceded subsequently inaccurate responses. Recordings from electrodes placed at left frontal, midline antero-central, and appropriately contralateral central and parietal sites were prominent in ERC patterns of subsequently accurate performances. This suggests that a distributed cortical 'preparatory network,' composed of distinct cognitive, integrative motor, somesthetic, and motor components, is essential for accurate visuomotor performance. ERC patterns related to feedback about accurate and inaccurate responses were similar to each other in the interval immediately after feedback onset, but began to differ in an interval spanning an early P300 peak. The difference became even greater in an interval spanning a late P300 peak. For both early and late P300 peaks, ERC patterns following feedback about inaccurate performance involved more frontal sites than did those following feedback about accurate performance. Together with the stimulus- and response-locked results presented in part I, results of this study on the preparatory and feedback periods suggest that ERCs show salient features of the rapidly shifting, functional cortical networks that are responsible for simple cognitive tasks. ERCs thus provide a new perspective on information processing in the human brain in relation to behavior--a perspective that supplements conventional EEG and ERP procedures.

Adult

Event-related covariances during a bimanual visuomotor task. I. Methods and analysis of stimulus- and response-locked data.

A new method that measures between-channel, event-related covariances (ERCs) from scalp-recorded brain signals has been developed. The method was applied to recordings of 26 EEG channels from 7 right-handed men performing a bimanual visuomotor judgment task that required fine motor control. Covariance and time-delay measures were derived from pairs of filtered, laplacian-derived, averaged wave forms, which were enhanced by rejection of outlying trials, in intervals spanning event-related potential components. Stimulus- and response-locked ERC patterns were consistent with functional neuroanatomical models of visual stimulus processing and response execution. In early post-stimulus intervals, ERC patterns differed according to the physical properties of the stimulus; in later intervals, the patterns differed according to the subjective interpretation of the stimulus. The response-locked ERC patterns suggested 4 major cortical generators for the voluntary fine motor control required by the task: motor, somesthetic, premotor and/or supplementary motor, and prefrontal. This new method may thus be an advancement toward characterizing, both spatially and temporally, functional cortical networks in the human brain responsible for perception and action.

Adult