Large, Adam
(2017)
THE ROLE OF SOMATOSTATIN-EXPRESSING INTERNEURONS IN ANTERIOR PIRIFORM CORTEX.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
At first approximation, the anterior piriform cortex (APC) appears to be a homogenous structure in terms of connectivity and sensory processing. Feedforward excitatory afferent input innervates the APC uniformly throughout the cortex, as does the local recurrent excitatory input. Odors are represented by a distributed ensemble of neurons spread throughout the APC, showing no obvious columnar structure or topography. Still, this supposed homogeneity belies the abundant diversity of inhibitory processes that may underlie sensory processing of the piriform cortex. Unfortunately, current understanding of inhibitory interneurons and their function is fairly coarse, limiting our ability to model olfactory processing. Our research was focused on clarifying the quality of inhibition in anterior piriform cortex, specifically focusing on Layer 3 somatostatin-expressing interneurons, which mediate recurrent, feedback inhibition. We first characterized the types of inhibition seen in the APC and their potential functions. Using electrical stimulation of APC fiber tracts, we measured the relative balance of feedforward and recurrent excitation and inhibition onto the three major classes of excitatory cells in piriform cortex to understand the relative roles for each type of input onto piriform principal cells. Then, we characterized the electrophysiological and functional properties of interneurons in APC, including somatostatin cells, to better understand the diversity of cells in olfactory cortex. Finally, we were interested in the role of inhibition in mediating principal cell activity. To do this, we used a novel technology - Targeted Recombination of Active Populations (TRAP) - to molecularly label active neurons during exploration of a novel odor environment. We found that neurons responding to an odor are not distributed uniformly across the APC, but rather on a gradient along the rostrocaudal axis. Using optogenetics, we found a spatial bias of inhibition onto pyramidal cells that corroborated the TRAP data, as well as discovering a subclass of interneurons that receive an opposing rostrocaudal bias of inhibition - suggesting a possible role for disinhibition in sensory processing. We determined that somatostatin cells are poised to mediate asymmetric inhibition onto interneurons, and therefore asymmetric disinhibition onto pyramidal cells.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID  |
|---|
| Committee Chair | Urban, Nathan | nurban@pitt.edu | nurban | UNSPECIFIED | | Committee Member | Oswald, Anne-Marie | amoswald@pitt.edu | amoswald | UNSPECIFIED | | Committee Member | Doiron, Brent | bdoiron@pitt.edu | bdoiron | UNSPECIFIED | | Committee Member | Barrionuevo, German | german@pitt.edu | german | UNSPECIFIED | | Committee Member | Kuhlman, Sandra | skuhlman@andrew.cmu.edu | UNSPECIFIED | UNSPECIFIED | | Committee Member | Dong, Yan | yandong@pitt.edu | yandong | UNSPECIFIED | | Committee Member | Wilson, Donald | donald.wilson@nyumc.org | UNSPECIFIED | UNSPECIFIED |
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| ETD Committee: |
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| Date: |
10 May 2017 |
| Date Type: |
Submission |
| Defense Date: |
7 April 2017 |
| Approval Date: |
26 June 2017 |
| Submission Date: |
13 April 2017 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
159 |
| 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: |
Neuroscience
Neural Circuits
Interneurons
Inhibition |
| Date Deposited: |
27 Jun 2017 00:09 |
| Last Modified: |
27 Jun 2017 00:09 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/31451 |
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