Salsovic, Joseph
(2023)
Somatosensory two-photon calcium imaging of nociceptive neuron populations in rodent ex vivo spinal cord.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Spinal dorsal horn disinhibition occurs in both development and painful neuropathies. In the naïve condition, heterogenous polymodal nociceptors of multiple tissue-types input into superficial lamina of the spinal dorsal horn, where local nociceptive neurons are controlled by inhibitory networks. However, it’s unknown how inhibitory networks carve out distinct excitatory population responses from these heterogenous peripheral inputs. To address this knowledge gap, we used two-photon calcium imaging of populations of excitatory neurons in the mouse superficial dorsal horn. We identify the cutaneous modalities and tissue-type convergence in populations of superficial excitatory neurons. We find that, in the naïve condition, a majority of superficial excitatory neurons are polymodal and respond to two or more modalities. These polymodal neurons however are a heterogenous group composed of neurons with distinct modality tunings. Next, we determine the level of tissue-type convergence in superficial excitatory neurons. We identify a population of neurons responsive to both cutaneous and musculoskeletal stimulation and find that they are mechanical, heat, and cold (MHC) responsive and mechanical-tuned. Finally, to determine the role of inhibitory networks in shaping these naïve populations, we pharmacologically instate spinal disinhibition and find an increase in polymodality with mechanical population tuning driven by low-threshold mechanical inputs. In summary, during disinhibition, heterogenous, multi-functional naïve populations with distinct modality tunings become strictly polymodal with mechanical tuning resulting in a loss of the neural organization that may drive normal pain percepts.
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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Unpublished |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 |
|---|
| Thesis Advisor | Koerber, H. Richard | | | | | Committee Chair | Ross, Sarah | | | | | Committee Member | Albers, Kathryn | | | | | Committee Member | Meriney, Stephen | | | | | Committee Member | Davis, Brian | | | | | Committee Member | Baccei, Mark | | | |
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| Date: |
15 September 2023 |
| Date Type: |
Publication |
| Defense Date: |
9 December 2022 |
| Approval Date: |
15 September 2023 |
| Submission Date: |
16 December 2022 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
180 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Somatosensory, Dorsal horn, disinhibition, polymodality, modality tuning, convergence, cutaneous, musculoskeletal, nociception, pain, multi-functionality |
| Date Deposited: |
15 Sep 2023 13:47 |
| Last Modified: |
15 Sep 2023 13:47 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44042 |
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