2014 — 2017 |
Baker, Michael Macagno, Eduardo [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Gap Junction Channel Composition and the Control of Neuronal Morphology and Connectivity @ University of California-San Diego
This project will generate new information on how an important family of proteins, the GAP Junction proteins, partakes in the assembly of a functional brain from its component parts, neurons and glial cells. These proteins join together to form electrical synapses, a major means of communication between nerve cells. During brain development, they help to define which cells can join together in functional circuits. Mutations in gap junction proteins can lead to devastating abnormalities in brain function. Experiments will be carried out in a simple animal with a simple brain, the medicinal leech, where interactions between small numbers of well-characterized nerve cells can be explored in greater depth, with diverse experimental approaches and tools. Since critical molecular mechanisms are highly conserved throughout evolution, these studies will advance the general understanding of how nervous systems are built, including those of more complex species, such as mammals. Additionally, leech neurobiology is ideally suited to undergraduate training, offering a strong foundation in molecular and cellular biology and electrophysiology. Student recruitment for this project will focus on Community College transfer students, particularly those from underrepresented groups, during the summer before they enter UCSD, to provide an early exposure to scientific research. Continuing their research experiences during their undergraduate careers, they will contribute to the badly needed increase of well-trained graduates in STEM fields.
The proposed studies will be based on recent findings that indicate that different types and distributions of gap junction proteins can regulate the shape and connectivity of individual leech neurons. Gap junction proteins belong to large gene families that form inter-cellular channels and allow direct exchange of ions and small molecules. Each channel is comprised of six protein subunits, and since many neurons express unique complements of multiple gap junction proteins that can form the channels, a cell's expression profile might function like lock-and-key recognition factors. This project will test how different gap junction proteins can affect the characteristic morphology and connectivity of identified neurons in the leech central nervous system. The expression and function of gap junction proteins will be modulated by gene knockdown and transgene expression in individual developing neurons, and morphological changes will be assayed by digitizing neuronal arbors using confocal microscopy and quantifying branch distribution, number and length. Intracellular dye-tracer injections and electrical recordings will detect changes in their connectivity.
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