Circuit Diagrams

 DESCRIPTION (provided by applicant): The brain is a remarkably complex organ comprised of hundreds of unique cell types that are organized to form sophisticated neural circuits. Although we have made progress toward understanding brain function and development, it is clear there is still much to be learned. Currently, all genome-wide methods that could be brought to bear on functional studies of the brain are destructive, meaning that as a genomic analysis is performed on a population of cells, the cells are destroyed.

 DESCRIPTION (provided by applicant): Examining neural circuits crucially relies on the ability to activate or silence individual circuit components to subsequently assess their impact on other parts of the circuit and their influence on behavior. Recent refinements of viral tools for gene delivery have allowed optogenetic methods to target cells based on specific cell types, localization, and connectivity. The physiological dissection of targeted circuits has been extremely successful in the mouse brain, but remains of limited use in non-human primate brain.

 DESCRIPTION (provided by applicant): Understanding the computations that take place in brain circuits will require identifying the wiring diagrams of those circuits. In recent years seveal new methods have been developed to identify the brain's wiring diagrams. Each of these methods have some strengths and limitations. Importantly, there is no available anterograde monosynaptic tracer that can be used to regulate gene expression of synaptically connected neurons in species ranging from drosophila to mice.

Project Summary: Hippocampal sharp-wave ripples are 150-250 Hz oscillations during slow-wave sleep or immobility during which large populations of hippocampal neurons sequentially replay activity patterns that occurred during exploration of the environment. Disruption of ripples during wakefulness disrupts working memory.

Our research goal is to determine the factors that instruct the development of visual responses in the mammalian retina. In particular, we are studying the developmental period when the retina transitions from generating retinal waves to mediating visual responses by forming functional circuits. Utilizing a high-speed volumetric two-photon microscope will enable the first description of spontaneous firing patterns across identified microcircuits, such as those that mediate direction selectivity.

PROJECT SUMMARY / ABSTRACT Epilepsy is an often debilitating neurological condition affecting 3 million Americans and more than 50 million people across the globe. Focal epileptic seizures start in specific brain regions due to abnormal patterns of activity in very specific subpopulations of neurons.

PROJECT SUMMARY The execution of learned sequential motor behaviors, like those involved in playing a well learned tune on the piano, are thought to be supported by precise sequences of neuronal activity in the brain. However, probing the ties between sequential neuronal activity, neuronal connectivity and behavior is challenging without methods for simultaneously observing and controlling neuronal activity with spatial and temporal precision.

This project will transfer a computational modeling technology, "StimVision", from the McIntyre Lab at Case Western Reserve University to the deep brain stimulation (DBS) group at Massachusetts General Hospital (MGH). DBS is currently used to treat severe obsessive-compulsive disorder (OCD) through high-frequency electrical stimulation of the ventral internal capsule/ventral striatum (VC/VS). VC/VS is a complex brain region containing white matter tracts projecting to multiple frontal cortical regions.

Project Summary/Abstract The hippocampus is one of a select few brain regions that retain the ability to generate neurons in adulthood. Research in human patients and animal models suggests that increases and decreases in neurogenesis alter memory function and contribute to the etiology and treatment of emotional disorders. Despite almost 15 years of research linking adult neurogenesis to memory and emotional regulation, almost nothing is known about the circuit and coding mechanisms through which adult neurogenesis influences these processes.

Project Summary/Abstract Synaptic plasticity is thought to be a basis of learning and memory of the brain. Signaling mechanisms underlying synaptic and behavioral plasticity have been extensively studied with the aid of pharmacological and genetic manipulation of signaling. However, it has been difficult to assess the spatiotemporal aspects of signaling activity particularly.