Research Description:

Optimizing Neuronal Tracer Chemistry to Determine the Detailed Topography of Brain Circuits Related to Neglect

I will be examining the neuroanatomy of hemispatial neglect, a complex neurological condition caused by a stroke.

I have previously worked with Dr. Reep over the past two years to explore the neuroanatomical circuitry of neglect.  Dr. Reep and his colleagues have created a rodent model of neglect for neuroanatomical studies and to develop possible pharmacological treatments.  Dr. Reep has found that that the medial agranular cortex(AGm), posterior parietal cortex (PPC) and dorsocentral striatum (DCS) are the main regions involved in neglect in rodents.  The lateral posterior nuclei of the thalamus (LP) was found to have extensive reciprocal connections with AGm, PPC, and DCS (the human homologue of LP is involved in neglect).  In addition, a recent study that I was involved in found that different regions of LP project to AGm in a segregated fashion.   Part of my project will be to further analyze these possible segregations and to determine any physiological implications.

In addition to analyzing these pathways, I will optimize the chemistry of the neuronal tracer, Dextran Amine (DA).  Most neuroanatomical studies utilize neuronal tracers, which are basically a dye that is injected into a certain region of the brain and transported through neurons.  Theses tracers can be transported retrogradely or anterogradely, and the mechanisms of transport is very sensitive to buffer chemistry.  I will use eight different combinations of buffer chemistry, using either an acidic or neutral pH, acetate or phosphate buffer, and 5 or 10 day survival time.  During this project, I will perform a craniotomy on groups of eight rats and inject two different fluorescent colors of the tracer DA into AGm.  After 5 or 10 day survival time, the brains will be removed and visualized under a fluorescent microscope.  The double labeled injection into different regions of AGm allows visualization of any segregation.

After completing this project, I hope to provide other neuroscience researchers a definitive recipe for the best visualization of neuronal tracers, and using this double-labeling method will allow us to visualize the segmentation of LP