Project description:To validate the sequence motifs identified by our multi-task learning model MTtrans, a new 5' UTR library with around 8,000 synthetic 5'UTRs was built to express EGFP. The reads count was used as a proxy of translation rate here to validate the estimated regulatory effect of motifs that we inferred from multiple datasets, proving the robustness of the sequence motifs.
Project description:While motor cortex is crucial for the learning of precise and reliable movements, whether astrocytes contribute to its plasticity and function during motor learning is unknown. Here we report that primary motor cortex (M1) astrocytes in mice show gene expression changes associated with learning a cued lever-push task, including changes in glutamate transport genes
Project description:To identify novel miRNAs involved in the regulation of learning and memory formation, we used the Morris water maze task to distinguish inbred wild-type C57BL/6J mice with good or poor learning and memory capability. C57BL/6J mice which undergo water maze task were sacrificed immediately after training. The hippocampus was harvested for miRNAs expression analysis with miRNA array (Phalanx Mouse & Rat miRNA OneArray® 2.0, annotation based on: miRBase release 15). These differentially expressed miRNAs were applied for further investigation.
Project description:A comprehensive landscape of epigenomic events regulated by the Reelin signaling through activation of specific cohort of cis-regulatory enhancer elements (LRN-enhancers), which involves the proteolytical processing of the LRP8 receptor by the gamma-secretase activity and is required for learning and memory behavior All ChIP-Seq experiments were designed to understand the unique signature and function of LRN-enhancers in signaling pathways of learning and memory.
Project description:Cellular diversification is a fundamental feature of the brain that is critical for physiological functions of the nervous system including perception, motor control, and learning and memory. Advances in single cell RNA-sequencing have led to characterization of transcriptomic profiles of distinct major types of neurons in the brain. However, how transcriptomic profiles diversify within a specific population of neurons and their links to function remain poorly understood. Purkinje neurons represent some of the most iconic cells in the brain with decades of research characterizing their anatomy, cell biology, physiology, and roles in plasticity, learning and memory, as well as in diseases of the nervous system. In this study, we deployed an approach of isolating nuclei tagged in specific cell types followed by cell sorting and single nuclear RNA sequencing to profile Purkinje neurons and their response to motor activity and learning in adult mice. We uncovered the molecular map of two major subpopulations of Purkinje neurons, identified by the hallmark genes Aldoc and Plcb4, which bear distinct transcriptomic features. Remarkably, Plcb4+, but not Aldoc+, Purkinje neurons display robust plasticity of gene expression in mice subjected to sensorimotor and learning experience with downregulation of gene clusters related to chromatin regulation and synaptic organization and upregulation of gene clusters related to neuronal activity and synaptic transmission and neuron-immune interactions. Using in vivo calcium imaging and optogenetics perturbation approaches, we show that activation of Plcb4+ Purkinje neuron plays a crucial role in associative motor learning. Upon integrating single nuclear RNA-seq datasets with weighted gene network analysis, we also identify a motor activity and learning specific gene module that includes components of the FGFR2-SOS1-MAPK signaling pathway in Plcb4+ Purkinje neurons. Knockout of FGFR2 in Plcb4+ Purkinje neurons in adult mice by a CRISPR approach dramatically disrupts motor learning. Our findings provide a platform for identification of subpopulations of neurons and define how diversification of Purkinje neurons in the cerebellum links to their responses to motor learning. Our study, and by extension similar studies in the human brain, will provide the foundation for understanding the selective vulnerability of Plcb4+ Purkinje neurons to neurological diseases.
Project description:Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions. RNA profiles from cognitively unimpaired and impaired aged rats were compared under 2 conditions: spatial learning task and a non-spatial learning task.