Jimenez, Daniel A.
(2013)
COMPETITIVE CELL-SPECIFIC INTEGRATION AND SURVIVAL OF ADULT-BORN NEURONS IN THE MOUSE OLFACTORY BULB.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
In several areas of the adult brain, notably the olfactory bulb, new neurons are generated and integrated into existing mature circuits. This observation raises questions about how an ongoing developmental process shapes adult brain circuitry and opens potential treatment avenues for neurological disorders such as traumatic brain injury, ischemia, depression, and degenerative diseases. In the networks where adult neurogenesis occurs, the integration of adult-born neurons is modulated by activity. The experiments in this dissertation are designed to address the hypothesis that adult-born neurons integrate into mature circuits in a competitive, activity-dependent manner.
Specifically, we sought to address the question of whether activity in adult-born neurons directly causes enhanced survival of particular active newborn neurons in a cell-autonomous fashion, or whether survival is a competitive process in which the most active cells in the network have the highest chance of survival. To differentiate between these two hypotheses required manipulating activity both of the adult-born neurons and other neurons within the network. Here we used both virus-mediated reduction of cell intrinsic activity and reduced sensory stimuli to show that survival is a competitive process in which the most active cells in the network have the highest chance of survival. RNA-based knockdown of Na+ channels resulted in decreased survival of adult-born neurons from 10-21 d.p.i. We then investigated the role of circuit level activity by inducing sensory deprivation through naris occlusion. Adult-born neurons with normal cell-intrinsic activity showed a reduction in survival in a sensory deprived circuit. But, interestingly, adult-born neurons with reduced intrinsic excitability showed an increased rate of survival in a sensory deprived circuit. These results provide important insights into the role of activity in the integration and therapeutic potential of neural stem cells in mature functional brain circuits.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Member | Barth, Alison L. | albarth@andrew.cmu.edu | | | | Committee Chair | Urban, Nathan N. | nurban@cmu.edu | | | | Committee Member | Amara, Susan G. | | | | | Committee Member | Lillien, Laura E. | | | | | Committee Member | Lois, Carlos | | | | | Committee Member | Monaghan-Nichols, Paula | | | |
|
| Date: |
29 January 2013 |
| Date Type: |
Publication |
| Defense Date: |
5 May 2011 |
| Approval Date: |
29 January 2013 |
| Submission Date: |
6 December 2012 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
229 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Neuroscience |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Adult Neurogenesis, Neural Stem Cells, Activity Dependent Plasticity, Olfactory Bulb |
| Date Deposited: |
29 Jan 2013 19:00 |
| Last Modified: |
29 Jan 2018 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/16819 |
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