Current Opinion in Neurobiology最新文献

Neurodevelopmental disorders (NDDs) affect 15% of children and are usually associated with intellectual disability, seizures, and autistic behaviors, among other neurological presentations. Mutations in a wide spectrum of gene families alter key stages of human brain development, leading to defects in neural circuits or brain architecture. Studies in animal systems have provided important insights into the pathobiology of several NDDs. Human stem cell technologies provide a complementary system that allows functional manipulation of human brain cells during developmental stages that would otherwise be inaccessible during human fetal brain development. Therefore, stem cell-based models advance our understanding of human brain development by revealing human-specific mechanisms contributing to the broad pathogenesis of NDDs. We provide a comprehensive overview of the latest research on two and three-dimensional human stem cell-based models. First, we discuss convergent cellular and molecular phenotypes across different NDDs that have been revealed by human iPSC systems. Next, we examine the contribution of in vitro human neural systems to the development of promising therapeutic strategies. Finally, we explore the potential of stem cell systems to draw mechanistic insight for the study of sex dimorphism within NDDs.

Epigenetic regulation of the genome is required for cell-type differentiation during organismal development and is especially important to generate the panoply of specialized cell types that comprise the brain. Here, we review how progressive changes in the chromatin landscape, both in neural progenitors and in postmitotic neurons, orchestrate the timing of gene expression programs that underlie first neurogenesis and then functional neuronal maturation. We discuss how disease-associated mutations in chromatin regulators can change brain composition by impairing the timing of neurogenesis. Further, we highlight studies that are beginning to show how chromatin modifications are integrated at the level of chromatin architecture to coordinate changing transcriptional programs across developmental including in postmitotic neurons.

The problem of drug addiction has become a profound societal problem worldwide. A better understanding of the neurobiological basis of addiction and the discovery of more effective treatments are needed. Recent studies have shown that many mechanisms that underlie addiction exist in more primitive organisms, including the nematode Caenorhabditis elegans (C. elegans). C. elegans is also hypothesized to possess a functional opioid-like system, including the endogenous opioid-like peptide NLP-24 and opioid-like receptor NPR-17. Opioids, such as morphine, are thought to cause addiction-like behavior by activating dopamine nerves in C. elegans via the opioid-like system. Accumulating evidence suggests that C. elegans is an excellent animal model for identifying molecular mechanisms of addiction.

The primate brain has evolved specialized visual capacities to navigate complex physical and social environments. Researchers studying cortical circuits underlying these capacities have traditionally favored the use of simplified tasks and brief stimulus presentations in order to isolate cognitive variables with tight experimental control. As a result, operational theories about visual brain function have come to emphasize feature detection, hierarchical stimulus encoding, top-down task modulation, and functional segregation in distinct cortical areas. Recently, however, experimental paradigms combining natural behavior with electrophysiological recordings have begun to offer a distinctly different portrait of how the brain takes in and analyzes its visual surroundings. The present article reviews recent work in this area, highlighting some of the more surprising findings in domains of social vision and spatial navigation along with shifts in thinking that have begun to emanate from this approach.