Small molecule profiling and imaging of the zebra finch song system

Amaya, Kensey R.

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Description

Title

Small molecule profiling and imaging of the zebra finch song system

Author(s)

Amaya, Kensey R.

Issue Date

2010-05-14T20:49:46Z

Director of Research (if dissertation) or Advisor (if thesis)

Clayton, David F.

Doctoral Committee Chair(s)

Cameron, Jo Ann

Committee Member(s)

• Clayton, David F.
• Sweedler, Jonathan V.
• Ceman, Stephanie S.
• Bellini, Michel

Department of Study

Cell & Developmental Biology

Discipline

Cell and Developmental Biology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• ToF-SIMS
• metabolomics
• songbird
• brain

Abstract

The ability of songbirds to communicate though learned vocalization and the discovery of discreet interconnected “song nuclei” involved in vocal learning has made them a valuable model to study the neuronal mechanisms behind learning and memory. This dissertation focuses on studying small molecules (i.e. lipids and metabolites) in the zebra finch song system, a songbird. I will use analytical tools and methods to detect and image the spatial distribution of small molecules (e.g. lipids) across the song system. In addition I will investigate changes in small molecules in the auditory lobule, a brain region involved in interpreting and processing auditory inputs, in response to song stimulation. Applying advances in Time of Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) small molecules (e.g. fatty acids) are detected and high spatial resolution images (2.3 μm) are generated, forming 11.5 megapixel chemical images using a sagittal brain section collected from an adult male zebra finch. ToF-SIMS analysis reveals a heterogeneous distribution of small molecules across the brain section corresponding to different anatomical structures, including two song nuclei that are important in song-motor control. Expanding upon the ToF-SIMS results I increase the number of identifiable small molecules; and expand the number of brain regions to include all of the major song nuclei in the zebra finch brain. Using ToF-SIMS and applying multivate statistical methods (e.g. principle component analysis) I show chemical differences between functionally distinct and tissue specific brain areas; as well as at different developmental stages in the male songbird brain. Metabolites are a diverse group of small molecules that act as end products and intermediates in biochemical pathways such as signaling molecules (i.e. dopamine), amino acids (i.e. glutamate) and in energy metabolism (i.e. glucose). Metabolomic studies focusing on the auditory lobule, a brain region involved in the acquisition, processing, and interpreting of auditory inputs, exhibited unique metabolomic profiles between birds exposed to novel song exposure, habituation song, and silence. Biochemical pathways involved in sugar metabolism (e.g. glycolysis), RNA synthesis, and GHB metabolism exhibit overall changes upon novel song stimulation compared to silent control birds. Integrating genomic data and metabolomic data suggests other biochemical pathways are responding to song stimulation. This dissertation reveals the heterogeneous distribution of small molecules across the major song nuclei in the zebra finch brain and at different developmental stages and the metabolomic response to song. These experiments serve as a stating point to study the role lipids play in the development of the song system and learning and memory. It also serves as a starting point to conduct more rigorous metabolomic studies and integrating metabolomic, genomic, and proteomic information to better study song response in the zebra finch brain.

Graduation Semester

2010-05

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Copyright and License Information

Copyright 2010 Kensey R. Amaya

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