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Jensen, D. R.

Publications and source records attributed to Jensen, D. R..

2 recordsLinked to original sources

Spatiotemporal Divergence Between Intrinsic And Evoked Cortical Activity Predicts Visual Detection.

The threshold for sensory detection varies with fluctuations in intrinsic cortical activity. When stimulus-encoding cortical populations are more excitable, stimuli elicit stronger neural responses that are more likely to be detected. However, the detection of a stimulus is also more likely when cortical populations are less excitable because there is less background "noise". Therefore, it is unclear how the variable states of intrinsic and sensory-evoked cortical activity and their interactions impact sensory detection. We hypothesize the answer depends on the spatiotemporal structure of intrinsic activity states across sensory encoding and non-encoding populations. To test this, we examined intrinsic and target-evoked population activity across cortical Area MT in common marmosets while they performed a threshold visual detection task. We compared detection performance based on target-evoked responses and the state of intrinsic activity in the larger surrounding population. We find that the intrinsic activity in the surrounding, non-encoding population predicted trial-by-trial detection performance better than the population encoding the target-evoked response. Furthermore, we find that the detection performance of the monkey was best predicted by the divergence in excitability between the encoding and surrounding non-encoding population. These findings suggest that, rather than a source of noise or irrelevant to sensory processing, the distributed spatiotemporal state of intrinsic activity directly influences how sensory signals are represented in cortical populations and can influence perceptual thresholds in visual detection. Significance StatementPrior research into how variability in neural activity impacts perception has often focused on neural populations that encode relevant sensory information. However, the role of variable intrinsic activity in nearby, non-encoding populations and their contribution to sensory representations is less well understood. We found that the state of intrinsic activity in non-encoding populations was a better predictor of performance on a threshold visual detection task than the evoked-response magnitude. These results suggest that the state activity in broader neural populations plays a larger role in sensory computations relevant to perceptual decisions than previously regarded.

neuroscience↗

Beyond Structural Bioinformatics for Genomics with Dynamics Characterization of an Expanded KRAS Mutational Landscape

ABSTRACTCurrent capabilities in genomic sequencing outpace functional interpretations. Our previous work showed that 3D protein structure calculations enhance mechanistic understanding of genetic variation in sequenced tumors and patients with rare diseases. The KRAS GTPase is among the critical genetic factors driving cancer and germline conditions. Because KRAS-altered tumors frequently harbor one of three classic hotspot mutations, nearly all studies have focused on these mutations, leaving significant functional ambiguity across the broader KRAS genomic landscape observed in cancer and non-cancer diseases. Herein, we extend structural bioinformatics with molecular simulations to study an expanded landscape of 86 KRAS mutations. We identify multiple coordinated changes strongly associated with experimentally established KRAS biophysical and biochemical properties. The patterns we observe span hotspot and non-hotspot alterations, which can all dysregulate Switch regions, producing mutation-restricted conformations with different effector binding propensities. We experimentally measured mutation thermostability and identified shared and distinct patterns with simulations. Our results indicate mutation-specific conformations which show potential for future research into how these alterations reverberate into different molecular and cellular functions. The data we present is not predictable using current genomic tools, demonstrating the added functional information derived from molecular simulations for interpreting human genetic variation. Key PointsPlease provide 3 bullet points summarizing the manuscripts contribution to the field (100 characters max per point) 1) We functionally grouped 86 distinct KRAS mutations using MD scores, demonstrating scalability for genomics 2) MD-based groups explain experimental differences and mechanistic information about mutant proteins 3) Demonstrated added functional information from simulations for interpreting human genetic variation

genomics↗