Neuronal substrates characterizing two stages in visual object recognition

AbstractVisual object recognition is classically believed to involve two stages: a perception stage in which perceptual information is integrated, and a memory stage in which perceptual information is matched with an object's representation. The transition from the perception to the memory stage can be slowed to allow for neuroanatomical segregation using a degraded visual stimuli (DVS) task in which images are first presented at low spatial resolution and then gradually sharpened. In this functional magnetic resonance imaging study, we characterized these two stages using a DVS task based on the classic model. To separate periods that are assumed to dominate the perception, memory, and post-recognition stages, subjects responded once when they could guess the identity of the object in the image and a second time when they were certain of the identity. Activation of the right medial occipitotemporal region and the posterior part of the rostral medial frontal cortex was found to be characteristic of the perception and memory stages, respectively. Although the known role of the former region in perceptual integration was consistent with the classic model, a likely role of the latter region in monitoring for confirmation of recognition suggests the advantage of recently proposed interactive models

FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD

Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation in vitro. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases