Literature context: ; RRID:AB_2301417 Bacterial and Virus Strains
The neonatal mammal faces an array of sensory stimuli when diverse neuronal types have yet to form sensory maps. How these inputs interact with intrinsic neuronal activity to facilitate circuit assembly is not well understood. By using longitudinal calcium imaging in unanesthetized mouse pups, we show that layer I (LI) interneurons, delineated by co-expression of the 5HT3a serotonin receptor (5HT3aR) and reelin (Re), display spontaneous calcium transients with the highest degree of synchrony among cell types present in the superficial barrel cortex at postnatal day 6 (P6). 5HT3aR Re interneurons are activated by whisker stimulation during this period, and sensory deprivation induces decorrelation of their activity. Moreover, attenuation of thalamic inputs through knockdown of NMDA receptors (NMDARs) in these interneurons results in expansion of whisker responses, aberrant barrel map formation, and deficits in whisker-dependent behavior. These results indicate that recruitment of specific interneuron types during development is critical for adult somatosensory function.
Literature context: cam Cat# ab34735; RRID:AB_2301417 Rabbit polyclonal anti-Cux1 San
Human brain evolution is associated with expansion and folding of the neocortex. Increased diversity in neural progenitor (NP) populations (such as basally located radial glia [RG], which reside in an enlarged outer subventricular zone [OSVZ]) likely contributes to this evolutionary expansion, although their characteristics and relative contributions are only partially understood. Through single-cell transcriptional profiling of sorted human NP subpopulations, we identified the primate-specific TMEM14B gene as a marker of basal RG. Expression of TMEM14B in embryonic NPs induces cortical thickening and gyrification in postnatal mice. This is accompanied by SVZ expansion, the appearance of outer RG-like cells, and the proliferation of multiple NP subsets, with proportional increases in all cortical layers and normal lamination. TMEM14B drives NP proliferation by increasing the phosphorylation and nuclear translocation of IQGAP1, which in turn promotes G1/S cell cycle transitions. These data show that a single primate-specific gene can drive neurodevelopmental changes that contribute to brain evolution.
Literature context: # ab34735 RRID:AB_2301417 STEM121 St
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration. Remarkably, cell death was dissociated from tangle formation in this natural 3D model of AD. Using genome-wide expression analysis, we observed upregulation of genes involved in myelination and downregulation of genes related to memory and cognition, synaptic transmission, and neuron projection. This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease.
Literature context: #ab34735, RRID:AB_2301417 Rabbit pol
Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2+ neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex.
Literature context: 828 (AB_443253), Satb2 ab34735 (AB_2301417), Ctip2 ab18465 (AB_2064130), T
SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.