PROJECT SUMMARY
 Interrogation of basic biological phenomena in the post-genome era relies heavily on high-throughput. sensitive technologies that provide molecular profiles of cells and tissues. High-dimensionality molecular measurements (e.g.. levels of mRNAs for many/all genes) can be readily accomplished in bulk samples and down to the single-cell level. producing comprehensive (???omics) profiles for given samples that address research needs. However. such techniques necessarily ignore the tissue localization of gene products in order to produce the high-dimensionality data.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. CIPN is a common clinical problem; approximately 30-40% of patients receiving neurotoxic chemotherapy will suffer from this condition and. unfortunately. there is no preventive treatment for CIPN. Our recent study on neurodegeneration suggests that cell cycle re-entry in peripheral neurons play a critical role in the development of CIPN and targeting neuronal cell cycle machinery may be a highly effective therapy for CIPN. To test this idea.

Identification of the mechanism(s) responsible for drug reinforcement is a key step in understanding the mechanism of reinforcement learning. but has so far proven elusive.The dopamine neurons of the ventral tegmental area and substantia nigra pars compacta. located within the ventral mesencephalon. are a central locus for drug reinforcement.Even a single exposure to cocaine is sufficient to alter the biophysical properties of AMPA receptors (AMPARs) on dopamine neurons.

Core instrumentation for the Biology Core to expand the flow cytometry capabilities.

The purpose of this grant is for the purchase of a Confocal Microscope for Core Research Support project.

The major goal is to increase primate holding capacity for the P51 base grant.

Basic Research

Cortical function is characterized by the dynamic interplay of two major forces: excitation and inhibition. A current belief is that dysfunction of inhibition. mediated by local GABAergic interneurons. leads to a wide range of neurological diseases such as epilepsy. autism. schizophrenia. PTSD. A well-established principle of the cortical circuit organization is that inhibition is local while excitation is both local and long-range; however. this ignores that inhibition may be long-range as well.

Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as epilepsy and Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities.

Alzheimer's disease (AD) is increasing in number as the U.S. and global population gets older. Despite
 enormous effort and expense. treatment remains at best modestly effective and no new drugs have been approved
 since 2003 [1.2]. The increasing interest in drug discovery through repositioning old drugs for new therapeutic
 applications throw light in the treatment for neurodegenerative diseases including AD [3].