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Large, Adam (2017) THE ROLE OF SOMATOSTATIN-EXPRESSING INTERNEURONS IN ANTERIOR PIRIFORM CORTEX. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Large, Adamlarge.adam.m@gmail.comaml142
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairUrban, Nathannurban@pitt.edunurbanUNSPECIFIED
Committee MemberOswald, Anne-Marieamoswald@pitt.eduamoswaldUNSPECIFIED
Committee MemberDoiron, Brentbdoiron@pitt.edubdoironUNSPECIFIED
Committee MemberBarrionuevo, Germangerman@pitt.edugermanUNSPECIFIED
Committee MemberKuhlman, Sandraskuhlman@andrew.cmu.eduUNSPECIFIEDUNSPECIFIED
Committee MemberDong, Yanyandong@pitt.eduyandongUNSPECIFIED
Committee MemberWilson, Donalddonald.wilson@nyumc.orgUNSPECIFIEDUNSPECIFIED
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairUrban, Nathannurban@pitt.edunurban
Committee MemberOswald, Anne-Marieamoswald@pitt.eduamoswald
Committee MemberDoiron, Brentbdoiron@pitt.edubdoiron
Committee MemberDong, Yanyandong@pitt.eduyandong
Committee MemberBarrionuevo, Germangerman@pitt.edugerman
Committee MemberKuhlman,
Committee MemberWilson,
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


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