Research Career Programs

Project Summary This application describes a 5-year plan to investigate the neural dynamics that underpin distortion in memory, integrating computational modeling approaches with functional neuroimaging (fMRI) and non-invasive brain stimulation techniques (TMS). The candidate, a cognitive neuroscientist with a background in memory consolidation and experience in fMRI and TMS methods, seeks new training in computational modeling and model-based fMRI analysis under the mentorship of Dr. Anna Schapiro and Dr. Sharon Thompson-Schill.

PROJECT SUMMARY Significance: Neural circuit assembly requires activity-dependent refinement of circuit architecture (e.g. plasticity) to produce stereotyped behavior. Neurons are particularly susceptible to functional and structural plasticity during early developmental windows called critical periods. It is clear that failure to terminate critical period plasticity adversely affects mature circuit function in both animal models and humans (e.g. autism and epilepsy), yet the mechanisms that close critical periods are largely unknown.

Project Summary/Abstract Alternative splicing of pre-mRNAs is extensively employed by the nervous system to expand the transcriptomic manifold. Regulated in specific cellular contexts by multiple RNA-binding proteins (RBPs), this process is a major contributor to cellular identity that acts orthogonally to transcriptional regulation and has been implicated in many neurodevelopmental disorders.

Project Summary/Abstract: Glial cells collectively outnumber neurons in the vertebrate brain, but mechanistic understanding of their molecular subtypes and functions is lacking. Ependymal cells, ciliated epithelial cells that line the brain ventricles and produce laminar flow of cerebral spinal fluid (CSF) with their many motile cilia, are one such enigmatic group of glia. Relatively little is known about them, even compared to other glial cell types.

PROJECT SUMMARY Insufficient sleep, sleep disorders, and resulting problems with health and cognition are increasingly common in the United States. Many sleep disorders may be associated with abnormal sleep homeostasis: an innate regulatory process that balances sleep need, sleep intensity, and sleep amount as a function of prior time spent awake. Sleep homeostasis requires a feedback circuit to maintain the system within defined limits. However, the cellular components and protein signaling pathways of this feedback circuit remain incompletely defined.

PROJECT ABSTRACT The nervous systems of animals are comprised of neurons connected by a large number of synapses. The resulting neural networks underlie animal behavior and contribute to the storage of learned information in many species. In humans, the miswiring of neural networks likely results in disorders of behavior, learning, and thought. For all these reasons, understanding the development, organization, and disruptions in neural circuits is vital. The goal of connectomics is to produce and study the maps of neuronal connections within nervous systems.

PROJECT SUMMARY Stroke-causing illness, disability, and early death is set to double worldwide within the next 15 years. Despite physical therapy, about 50% of stroke survivors have impaired hand function, which strongly impacts activities of daily living and independence; novel treatment methods are urgently required.

PROJECT SUMMARY Attention is comprised of several component processes, including sustained attention, selective attention, and attentional flexibility. The first phase, the initial focusing of attention, precludes engagement of other components making it an important building block of many of our more complex behaviors.

PROJECT SUMMARY/ABSTRACT In order to understand neurological diseases, it is essential to identify the affected neuronal cell types, create model systems that accurately recapitulate normal function and disease phenotypes, and develop tools that allow cellular manipulations. Motor neurons in the spinal cord control body movement by communicating central motor commands with muscle targets.

Project Summary Cortical interneurons (cINs) are inhibitory cells that are born in surplus far from the cortex. During prenatal timepoints, cIN precursors migrate into the mouse visual cortex (V1) where only a fraction are selected to survive. Once integrated into the V1 circuit, cINs expressing parvalbumin (PV) or somatostatin (SST) trigger a temporally restricted period of plasticity that is required for normal visual experience. The underlying molecular factors and the role cellular activity plays in the selection of cIN survival and cIN-mediated plasticity are not fully understood.