Oxford open neuroscience最新文献

Expectations, derived from previous experience, can help in making perception faster, more reliable and informative. A key neural signature of perceptual expectations is expectation suppression, an attenuated neural response to expected compared with unexpected stimuli. While expectation suppression has been reported using a variety of paradigms and recording methods, it remains unclear what neural modulation underlies this response attenuation. Sharpening models propose that neural populations tuned away from an expected stimulus are particularly suppressed by expectations, thereby resulting in an attenuated, but sharper population response. In contrast, dampening models suggest that neural populations tuned toward the expected stimulus are most suppressed, thus resulting in a dampened, less redundant population response. Empirical support is divided, with some studies favoring sharpening, while others support dampening. A key limitation of previous neuroimaging studies is the ability to draw inferences about neural-level modulations based on population (e.g. voxel) level signals. Indeed, recent simulations of repetition suppression showed that opposite neural modulations can lead to comparable population-level modulations. Forward models provide one solution to this inference limitation. Here, we used forward models to implement sharpening and dampening models, mapping neural modulations to voxel-level data. We show that a feature-specific gain modulation, suppressing neurons tuned toward the expected stimulus, best explains the empirical fMRI data. Thus, our results support the dampening account of expectation suppression, suggesting that expectations reduce redundancy in sensory cortex, and thereby promote updating of internal models on the basis of surprising information.

Unlike mammals, vertebrates such as fishes and frogs exhibit remarkable tissue regeneration including the central nervous system. Retina being part of the central nervous system has attracted the interest of several research groups to explore its regenerative ability in different vertebrate models including mice. Fishes and frogs completely restore the size, shape and tissue structure of an injured retina. Several studies have unraveled molecular mechanisms underlying retina regeneration. In teleosts, soon after injury, the Müller glial cells of the retina reprogram to form a proliferating population of Müller glia-derived progenitor cells capable of differentiating into various neural cell types and Müller glia. In amphibians, the transdifferentiation of retinal pigment epithelium and differentiation of ciliary marginal zone cells contribute to retina regeneration. In chicks and mice, supplementation with external growth factors or genetic modifications cause a partial regenerative response in the damaged retina. The initiation of retina regeneration is achieved through sequential orchestration of gene expression through controlled modulations in the genetic and epigenetic landscape of the progenitor cells. Several developmental biology pathways are turned on during the Müller glia reprogramming, retinal pigment epithelium transdifferentiation and ciliary marginal zone differentiation. Further, several tumorigenic pathways and gene expression events also contribute to the complete regeneration cascade of events. In this review, we address the various retinal injury paradigms and subsequent gene expression events governed in different vertebrate species. Further, we compared how vertebrates such as teleost fishes and amphibians can achieve excellent regenerative responses in the retina compared with their mammalian counterparts.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional modification that diversifies protein functions by recoding RNA or alters protein quantity by regulating mRNA level. A-to-I editing is catalyzed by adenosine deaminases that act on RNA. Millions of editing sites have been reported, but they are mostly found in non-coding sequences. However, there are also several recoding editing sites in transcripts coding for ion channels or transporters that have been shown to play important roles in physiology and changes in editing level are associated with neurological diseases. These editing sites are not only found to be evolutionary conserved across species, but they are also dynamically regulated spatially, developmentally and by environmental factors. In this review, we discuss the current knowledge of A-to-I RNA editing of ion channels and receptors in the context of their roles in physiology and pathological disease. We also discuss the regulation of editing events and site-directed RNA editing approaches for functional study that offer a therapeutic pathway for clinical applications.

The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general.

The brain represents an organ with a particularly high diversity of genes that undergo post-transcriptional gene regulation through multiple mechanisms that affect RNA metabolism and, consequently, brain function. This vast regulatory process in the brain allows for a tight spatiotemporal control over protein expression, a necessary factor due to the unique morphologies of neurons. The numerous mechanisms of post-transcriptional regulation or translational control of gene expression in the brain include alternative splicing, RNA editing, mRNA stability and transport. A large number of trans-elements such as RNA-binding proteins and micro RNAs bind to specific cis-elements on transcripts to dictate the fate of mRNAs including its stability, localization, activation and degradation. Several trans-elements are exemplary regulators of translation, employing multiple cofactors and regulatory machinery so as to influence mRNA fate. Networks of regulatory trans-elements exert control over key neuronal processes such as neurogenesis, synaptic transmission and plasticity. Perturbations in these networks may directly or indirectly cause neuropsychiatric and neurodegenerative disorders. We will be reviewing multiple mechanisms of gene regulation by trans-elements occurring specifically in neurons.

Memory is the brain faculty to store and remember information. It is a sequential process in which four different phases can be distinguished: encoding or learning, consolidation, storage and reactivation. Since the discovery of the first Drosophila gene essential for memory formation in 1976, our knowledge of its mechanisms has progressed greatly. The current view considers the existence of engrams, ensembles of neuronal populations whose activity is temporally coordinated and represents the minimal correlate of experience in brain circuits. In order to form and maintain the engram, protein synthesis and, probably, specific transcriptional program(s) is required. The immediate early gene response during learning process has been extensively studied. However, a detailed description of the transcriptional response for later memory phases was technically challenging. Recent advances in transcriptomics have allowed us to tackle this biological problem. This review summarizes recent findings in this field, and discusses whether or not it is possible to identify a transcriptional trace for memory.

The initiation of nascent projections, or neurites, from the neuronal cell body is the first stage in the formation of axons and dendrites, and thus a critical step in the establishment of neuronal architecture and nervous system development. Neurite formation relies on the polarized remodelling of microtubules, which dynamically direct and reinforce cell shape, and provide tracks for cargo transport and force generation. Within neurons, microtubule behaviour and structure are tightly controlled by an array of regulatory factors. Although microtubule regulation in the later stages of axon development is relatively well understood, how microtubules are regulated during neurite initiation is rarely examined. Here, we discuss how factors that direct microtubule growth, remodelling, stability and positioning influence neurite formation. In addition, we consider microtubule organization by the centrosome and modulation by the actin and intermediate filament networks to provide an up-to-date picture of this vital stage in neuronal development.

The balance between proliferation and quiescence of stem cells is crucial in maintaining tissue homeostasis. Neural stem cells (NSCs) in the brain have the ability to be reactivated from a reversible quiescent state to generate new neurons. However, how NSCs transit between quiescence and reactivation remains largely elusive. Drosophila larval brain NSCs, also known as neuroblasts, have emerged as an excellent in vivo model to study molecular mechanisms underlying NSC quiescence and reactivation. Here, we discuss our current understanding of the molecular mechanisms underlying the reactivation of quiescent NSCs in Drosophila. We review the most recent advances on epigenetic regulations and microtubule cytoskeleton in Drosophila quiescent NSCs and their cross-talk with signaling pathways that are required in regulating NSC reactivation.