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Chen, A. B.

Publications and source records attributed to Chen, A. B..

2 recordsLinked to original sources

Encoding the expectation of a sensory stimulus

Most organisms possess an ability to differentiate unexpected or surprising sensory stimuli from those that are repeatedly encountered. How is this sensory computation performed? We examined this issue in the locust olfactory system. We found that odor-evoked responses in the antennal lobe (downstream to sensory neurons) systematically reduced upon repeated encounters of a temporally discontinuous stimulus. Rather than confounding information about stimulus identity and intensity, neural representations were optimized to encode equivalent stimulus-specific information with fewer spikes. Further, spontaneous activity of the antennal lobe network also changed systematically and became negatively correlated with the response elicited by the repetitive stimulus (i.e. a negative image). Notably, while response to the repetitive stimulus reduced, exposure to an unexpected/deviant cue generated undamped and even exaggerated spiking responses in several neurons. In sum, our results reveal how expectation regarding a stimulus is encoded in a neural circuit to allow response optimization and preferential filtering.

neuroscience

Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks

Poly(ADP ribose) polymerase inhibitors (PARPi) target cancer cells deficient in homology-directed repair of DNA double-strand breaks (DSBs). In preclinical models, PARPi resistance is tied to altered nucleolytic processing (resection) at the 5 ends of a DSB. For example, loss of 53BP1 or Rev7/MAD2L2/FANCV derepresses resection to drive PARPi resistance, although the mechanisms are poorly understood. Long-range resection can be catalyzed by two machineries: the exonuclease Exo1, or the combination of a RecQ helicase and Dna2. Here, we develop a single cell microscopy assay that allows the distinct phases and machineries of resection to be interrogated simultaneously in living S. pombe cells. Using this assay, we find that the 53BP1 orthologue and Rev7 specifically repress long-range resection through the RecQ helicase-dependent pathway, thereby preventing hyper-resection. These results suggest that \"rewiring\" of BRCA1-deficient cells to employ an Exo1-independent hyper-resection pathway is a driver of PARPi resistance.

genetics