2004 — 2006 |
Brown, Solange P |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Local Excitatory Networks in the Neocortex
[unreadable] DESCRIPTION (provided by applicant): The goal of this proposal is to characterize local synaptic interactions among functionally identified pyramidal cells in the visual cortex. Specific populations of pyramidal cells will be retrogradely labeled with fluorescent markers injected at their long-range axonal targets. By recording simultaneously from multiple labeled neurons in brain slices, we will characterize local synaptic interactions among identified subtypes of pyramidal cells. We will address three specific questions: Aim 1, do pyramidal neurons that project to a common subcortical target selectively connect to each other? Aim 2, does the spatial extent of local connectivity differ among different types of pyramidal cells? Aim 3, do synapses exhibit similar forms of short-term plasticity when grouped as a homogeneous class of connections between functionally defined synaptic partners? The results of these experiments will test (a) whether pyramidal cells connect non-selectively to other neurons or (b) whether each class of pyramidal neuron targets specific partners, forming local excitatory networks within the cortex. These studies will allow us to analyze mouse models of diseases like epilepsy and autism thought to result from aberrant connectivity among neocortical neurons. [unreadable] [unreadable]
|
0.954 |
2016 — 2020 |
Brown, Solange P |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
The Functional Organization of the Claustrum @ Johns Hopkins University
PROJECT SUMMARY: Brown, Solange P., Johns Hopkins University The broad goal of this proposal is to understand the types of cortical information that are integrated within the claustrum, a poorly understood brain structure that forms extensive reciprocal connections with the cortex. Studies have correlated abnormalities in the size and the activity of the claustrum with neuropsychiatric symptoms in diseases like Alzheimer's disease and schizophrenia, but the function of the claustrum remains unclear. A number of theories have been proposed regarding the claustrum's role in sensory processing and cognition, but the paucity of information on its cellular and functional organization has made it difficult to validate any of these theories. The proposed study will elucidate the cellular and functional organization of the claustrum to test three major current hypotheses: 1) that the claustrum plays a role in multimodal sensory integration, 2) that the claustrum plays a role in the bilateral coordination of sensorimotor behaviors involved in the exploration of the environment, and 3) that the claustrum plays a role in top-down control of the cortical response to sensory input. To test these hypotheses, we will use an innovative combination of approaches including rabies-based trans-synaptic tracing approaches, unitary recordings of synaptic connections among retrogradely and genetically labeled neurons, optogenetic circuit-mapping techniques, and in vivo studies. By assessing these theories of claustral function, we will determine mechanisms by which the claustrum influences cortical activity in the healthy brain and provide important insights into its contributions to abnormalities in sensory processing and cognition in neurologic and psychiatric diseases.
|
1 |
2017 — 2021 |
Brown, Solange Goff, Loyal |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Cell-Type Specific Gene Expression Differences Induced by Experience-Dependent Plasticity @ Johns Hopkins University
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.
|
0.915 |