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Barr, C.

Publications and source records attributed to Barr, C..

6 recordsLinked to original sources

Parvalbumin and somatostatin inhibitory microcircuits perform distinct roles in stereo matching

We readily perceive stereoscopic depth in correlated random dot stereograms (RDS), in which every dot presented to one eye has a matching dot in the other eye. In contrast, anti-correlated RDS, in which corresponding dots have opposite contrast polarity between the two eyes, do not evoke a perception of depth. Nevertheless, anti-correlated RDS still generate local same-polarity matches within the receptive fields of individual neurons. Inhibitory circuitry has been proposed to suppress these false matches and thereby prevent the perception of illusory depth. To investigate how inhibitory circuits in visual cortex contribute to this process, we measured disparity selectivity to correlated and anti-correlated RDS in two major classes of inhibitory neurons in mice: parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) neurons. We found that the disparity tuning of PV+ neurons was highly correlated with the average activity of surrounding neurons. In contrast, the disparity tuning of SST+ neurons was poorly predicted by local population activity, suggesting that PV+ and SST+ neurons integrate excitatory inputs through distinct mechanisms. Optogenetic suppression of PV+ or SST+ neurons further revealed divergent functional roles. Although both cell types contributed to sharpening selectivity for correlated RDS, only SST+ neurons reduced selectivity for anti-correlated RDS. These findings suggest that PV+ and SST+ circuits both enhance responses to correct binocular matches in correlated RDS, whereas SST+ circuits contribute to suppressing false matches in anti-correlated RDS.

neuroscience↗

Degraded mapping of disparity tuning in visual cortex explains deficits in binocular depth perception

Sensory cortex is highly organized, but the function of this organization is contentious. We show that closing one eye during the developmental critical period in juvenile mice (monocular deprivation) caused lasting impairments in binocular depth perception and disrupted cortical maps of binocular disparity tuning. In normal mice, disparity tuning was concentrated in the central visual field, particularly with respect to azimuth and in higher visual areas (HVAs). Additionally, neurons transitioned from encoding nearer to farther stereoscopic depths from the center toward the peripheral visual field, especially along elevation and within HVAs. Monocular deprivation did not reduce overall disparity selectivity across the neuronal population, but rather weakened the retinotopic and hierarchical organization of disparity tuning and reduced trial-to-trial reliability of neuronal responses. Analysis of single-trial responses from neurons tuned to near disparities showed that this reduced response reliability is sufficient to explain the impaired depth discrimination observed in deprived mice.

neuroscience↗

Interactions between saccades and smooth pursuit eye movements in marmosets

Animals use a combination of eye movements to track moving objects. These different eye movements need to be coordinated for successful tracking, requiring interactions between the systems involved. Here, we study the interaction between the saccadic and smooth pursuit eye movement systems in marmosets. Using a single target pursuit task, we show that saccades cause an enhancement in pursuit following a saccade. Using a two-target pursuit task, we show that this enhancement in pursuit is selective towards the motion of the target selected by the saccade, irrespective of any biases in pursuit prior to the saccade. These experiments highlight the similarities in the functioning of saccadic and smooth pursuit eye movement systems across primates. SIGNIFICANCE STATEMENTWe study the coordination between the smooth-pursuit and saccadic eye movement systems in marmosets using single and multiple object motions. We find that saccade to a target increases pursuit velocity towards the target. If multiple objects are visible, saccade choice makes pursuit more selective towards the saccade target. Our results show that coordination between different eye movement systems to successfully track moving objects is similar between marmosets and primates.

neuroscience↗

Targeted analysis of dyslexia-associated regions on chromosomes 6, 12 and 15 in large multigenerational cohorts

Dyslexia is a common specific learning disability with a strong genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date investigated only limited genomic variation within each locus with no confirmed pathogenic variants. In a collection of >2000 participants in families enrolled at three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate dyslexia risk genes (DNAAF4, CYP19A1, DCDC2, KIAA0319 and GRIN2B) for which prior evidence of association exists from more than one sample. For each of six dyslexia-related phenotypes we used both individual-single nucleotide polymorphism (SNP) and aggregate testing of multiple SNPs to evaluate evidence for association. We detected no promoter alterations and few potentially deleterious variants in the coding exons, none of which showed evidence of association with any phenotype. All genes except DNAAF4 provided evidence of association, corrected for the number of genes, for multiple non-coding variants with one or more phenotypes. Results for a variant in the downstream region of CYP19A1 and a haplotype in DCDC2 yielded particularly strong statistical significance for association. This haplotype and another in DCDC2 affected performance of real word reading in opposite directions. In KIAA0319, two missense variants annotated as tolerated/benign associated with poor performance on spelling. Ten non-coding SNPs likely affect transcription factor binding. Findings were similar regardless of whether phenotypes were adjusted for verbal IQ. Our findings from this large-scale sequencing study complement those from genome-wide association studies (GWAS), argue strongly against the causative involvement of large-effect coding variants in these five candidate genes, support an oligogenic etiology, and suggest a role of transcriptional regulation. Author SummaryFamily studies show that genes play a role in dyslexia and a small number of genomic regions have been implicated to date. However, it has proven difficult to identify the specific genetic variants in those regions that affect reading ability by using indirect measures of association with evenly spaced polymorphisms chosen without regard to likely function. Here, we use recent advances in DNA sequencing to examine more comprehensively the role of genetic variants in five previously nominated candidate dyslexia risk genes on several dyslexia-related traits. Our analysis of more than 2000 participants in families with dyslexia provides strong evidence for a contribution to dyslexia risk for the non-protein coding genetic variant rs9930506 in the CYP19A1 gene on chromosome 15 and excludes the DNAAF4 gene on the same chromosome. We identified other putative causal variants in genes DCDC2 and KIAA0319 on chromosome 6 and GRIN2B on chromosome 12. Further studies of these DNA variants, all of which were non-coding, may point to new biological pathways that affect susceptibility to dyslexia. These findings are important because they implicate regulatory variation in this complex trait that affects ability of individuals to effectively participate in our increasingly informatic world.

genetics↗

Mammals achieve common neural coverage of visual scenes using distinct sampling behaviors

Most vertebrates use head and eye movements to quickly change gaze orientation and sample different portions of the environment with periods of stable fixation. Visual information must be integrated across several fixations to construct a more complete perspective of the visual environment. In concert with this sampling strategy, neurons adapt to unchanging input to conserve energy and ensure that only novel information from each fixation is processed. We demonstrate how adaptation recovery times and saccade properties interact, and thus shape spatiotemporal tradeoffs observed in the motor and visual systems of different species. These tradeoffs predict that in order to achieve similar visual coverage over time, animals with smaller receptive field sizes require faster saccade rates. Indeed, we find comparable sampling of the visual environment by neuronal populations across mammals when integrating measurements of saccadic behavior with receptive field sizes and V1 neuronal density. We propose that these mammals share a common statistically driven strategy of maintaining coverage of their visual environment over time calibrated to their respective visual system characteristics.

neuroscience↗

Ocular following eye movements in marmosets follow complex motion trajectories

Ocular following eye movements help stabilize images on the retina and offer a window to study motion interpretation by visual circuits. We use these ocular following eye movements to study motion integration behavior in the marmosets. We characterize ocular following responses in the marmosets using different moving stimuli such as dot patterns, gratings, and plaids. The marmosets can accurately track motion along different directions and exhibit spatial frequency and speed sensitivity that closely matches the sensitivity reported in neurons from their motion selective area MT. Marmosets are also able to track the integrated motion of plaids, with tracking direction consistent with intersection of constraints model of motion integration. Marmoset ocular following responses are similar to responses in macaques and humans with certain species-specific differences in peak sensitivities. Such motion sensitive eye movement behavior in combination with direct access to cortical circuitry makes the marmoset model well suited to study the neural basis of motion integration. Significance statementOcular following is a reflexive eye tracking behavior in response to large visual field motion. It reflects the properties of underlying motion sensing circuits. One of the primary motion sensing areas in primates is area MT. In the primate species of marmosets, this and other cortical areas are easily accessible due to their lissencephalic brain. We demonstrate ocular following behavior in the marmosets for simple and complex motion trajectories and describe its characteristics. We then use ocular following to distinguish between different motion integration models. Our results show the utility of ocular following to study the neural basis for motion sensing in marmosets.

neuroscience↗