An organism's ability to adapt to its environment is essential for its survival and results from modifications to its nervous system. These experience-dependent changes in the function of brain circuits contribute to many fundamental processes including development, learning, and memory. Long-term changes in the organization of the nervous system in response to experience depend in part on the set of genes expressed in neurons. However, the nervous system is made up of many different types of neurons. Whether changes in gene expression in response to experience are similar across different types of neurons or whether each type responds in its own way is not well understood. Furthermore, whether different types of experiences cause the same gene expression changes in a particular type of neuron is also not clear. This project will leverage several new developments to analyze the gene expression changes induced in single, identified neurons by changes in experience to address these questions. In addition, as the investigators develop and use powerful new techniques to address these questions at the resolution of single neurons, they will generate materials to train other scientists and students to analyze these types of data so that these techniques can be applied to other important biological questions. The results from these studies are expected to advance our knowledge of how the nervous system implements long term changes induced by experience to affect such fundamental processes as development, learning and memory.
Experience-dependent plasticity underlies many fundamental processes in the nervous system including development, learning, and memory. However, the molecular mechanisms underlying these changes remain poorly understood. Even less understood is the heterogeneity of cellular responses to induction of plasticity. This proposal addresses two fundamental questions: 1) Do different classes of cortical projection neuron engage similar plasticity mechanisms or exhibit cell type-specific transcriptional responses to experience-dependent plasticity? and 2) Does experience-dependent plasticity evoked by different sensory modalities engage similar molecular mechanisms or exhibit modality-specific transcriptional responses? Using single cell RNA-sequencing, the investigators will analyze the transcriptional profiles of distinct neuronal types within sensory cortex and identify common and cell type-specific molecular changes induced by well-established paradigms of experience-dependent plasticity. In addition, the investigators will develop a publicly accessible, interactive website to rapidly disseminate the gene expression data generated by the project to the broader scientific community, to educate scientists and other interested students in approaches for analyzing and interpreting these types of data in this rapidly developing field, and to share new analytical tools developed during the project. Together, these studies will generate mechanistic insights into the heterogeneity of the transcriptional responses to experience-dependent plasticity.
