Huntington’s disease (HD) is the most common inherited neurodegenerative disorder, and is characterized by early and most dramatic loss of neurons in the caudate and putamen as well as a debilitating triad of cognitive, motor, and psychiatric symptoms. The huntingtin gene was first linked to HD over twenty years ago, yet to date there is neither a precise molecular explanation for the cell loss that is seen in human patients, nor a curative therapeutic. In my talk, I will describe our efforts over the last few years to advance our understanding of the mechanistic basis of HD. We have combined the use of cell type-specific gene expression profiling with in vivo genetic screening to reveal transcriptional pathways perturbed by mutant Huntingtin protein, as well as the genes that help neurons survive in HD.
Thesis Defense Seminar
The Datta lab studies how information from the outside world is detected, encoded in the brain, and transformed into meaningful behavioral outputs. We address this problem by characterizing the olfactory system, the sensory modality used by most animals to interact with their environment. Here, we describe a novel molecular and circuit mechanism that underlies odor perception, one that may be specialized for the detecting and processing of odors with innate meaning. We also describe recent experiments using a combination of volumetric population imaging in awake mice and behavioral analysis to explore odor codes in piriform cortex, the main cortical center devoted to olfaction in the mammalian brain; these experiments identify an invariant representation for odor space in cortex, thereby suggesting mechanisms through which the olfactory system can link chemically-related odors to similar behaviors and perceptual qualities both within and across individuals.
This seminar has been canceled.
Thesis Defense Seminar
Among our senses, mechanical-sensing is the least well understood in part due to the difficulties in identifying and studying mechanical-sensitive channels that mediate the fist step of mechano-sensing. A group of Drosophila sensory neurons known as dendritic arborization (da) neurons have been used extensively for studying dendrite morphogenesis. It turns out that all da neurons are mechanical-sensitve and they are well suited for studying mechanical-sensitive channels such as Piezo, NompC and TMC. I will discuss our recent progress in this research area. There is also increasing evidence that mechano-sensitive channels play significant roles in several developmental processes. I will talk about their roles in axon/dendrite regeneration.
Neural circuitry represents sensory input with patterns of activity within populations of individual neurons. These representations are transformed across brain areas into representations that drive adaptive behavior. The circuitry across which transformations occur often extend over many millimeters: the mesoscale level or organization. Imaging at the mesoscale with micron resolution, deep in brain tissue that badly scatters light, with subsecond time resolution is a challenging optical problem. Here, we used new multiphoton imaging technology to measure representations across multiple visual cortical areas simultaneously in mice. By measuring shared variability for pairs of neurons within or across cortical areas, we obtained measurements of correlational structure, which can constrain models of circuit connectivity and mechanisms for transforming neural representations. In the course of this work, we also uncovered new principles for the organization of spatiotemporal and orientation tuning among visual cortex neurons. Together, these findings are illuminating how visual stimuli are represented in primary and higher visual areas in mice, and how these areas can be connected to each other.