The amygdaloid complex is involved in the """"""""processing"""""""" of multiple behaviors including fear, anxiety and learning and memory. There is also evidence that biochemical changes occur in the amygdala as a result of disease including schizophrenia, bipolar disease and cocaine and opiate abuse. The neuronal circuitry connecting various nuclei of the amygdala allowing internuclei communication has also been elucidated for aspects of fear conditioning. Given the central role of the amygdala in processing various types of CNS information an elucidation of the relative levels of mRNA abundance for the mRNAs that are present in the amygdala might provide insight into what neurochemical signals the amygdala responds to. Further since neuronal pathways have been dissected characterization of the expression profile in individual interconnected nuclei may provide information about how one region of the amygdala transfers information to another. We propose to generate molecular fingerprints of neurons within different regions of the amygdala using single cell and single nuclei aRNA amplification and microarray analysis in normal mice. Additionally we will determine how the profiles of these nuclei change in a mouse pharmacological model of bipolar disease involving amygdala response to withdrawal from lithium after chronic lithium treatment. As part of this proposal we propose to robotize the aRNA amplification procedure so that we can generate l000 individual sample templates each partitioned into an individual well in 96 well plates. While we are not proposing to perform 1000 microarray experiments (samples will be pooled as described in the text) having individual cells will permit each to be analyzed separately as required. In an effort to create a National resource of expression profiling data and amplified cells from the amygdala for use by other investigators the normal sample plates will be made available to anyone who requests them on a cost basis. The normal sample expression profiling data will be made available on a public website as soon as the data is confirmed by two array analyses. These data should be useful to investigators studying the amygdala as well as to """"""""bioinformaticists"""""""" who are in need of large data sets from multiple samples. Such large data sets should prove useful in the development of pattern search algorithms that are sorely needed to property analyze such complex gene expression data sets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH062813-01
Application #
6292163
Study Section
Special Emphasis Panel (ZMH1-BRB-P (02))
Program Officer
Baughman, Robert W
Project Start
2000-09-19
Project End
2002-08-31
Budget Start
2000-09-19
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$188,025
Indirect Cost
Name
University of Pennsylvania
Department
Pharmacology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hinkle, David A; Eberwine, James H (2003) Single-cell molecular biology: implications for diagnosis and treatment of neurologic disease. Biol Psychiatry 54:413-7