Moschonas, Eleni Haritomeni
(2024)
Cholinergic Neurotransmission During Performance of a Sustained Attention Task after
Traumatic Brain Injury.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Attentional deficits are prevalent following traumatic brain injury (TBI), and treatment options are limited due to an inadequate understanding of their etiology. Attentional functioning relies on an intact cholinergic network originating in the nucleus basalis of Meynert (nbM) and projecting to the medial prefrontal cortex (mPFC). In vivo microdialysis studies in non-TBI rats show task-evoked increases in acetylcholine (ACh) in the mPFC correlating with attentional performance, such studies are lacking in preclinical TBI models. It was hypothesized that TBI would decrease in vivo task-evoked release of ACh in the mPFC, correlating with impaired real-time performance on the 3-Choice Serial Reaction Time Test (3-CSRT) and with cholinergic neuron morphology reflective of a neurodegenerative phenotype in the nbM. Adult male rats (3-4 months old) trained in the 3-CSRT to the 2-s cue duration received either a moderate right controlled cortical impact or a Sham injury (n=10/group). On post-injury day (PID) 14, a guide cannula was surgically implanted in the right mPFC. At PID 21, dialysate samples were collected before and during 3-CSRT testing. Samples underwent analysis via high performance liquid chromatograph. After testing, rats underwent subsequent daily 3-CSRT testing for 5 days. At PID 26, cresyl violet staining was used to quantify cortical lesion volume and verify probe placement. Morphological assessments of cholinergic neurons in the contralateral and ipsilateral nbM were reconstructed and analyzed via Interactive Microscopy Image Analysis software (IMARIS). TBI rats exhibited significant deficits in sustained attention compared to their baseline performance and the Sham group. There were no differences in basal ACh efflux between Sham groups (p>0.05). After 3-CSRT onset, Sham rats showed a significant increase in task-related ACh release in the mPFC compared to both their baseline (p<0.05) and the TBI group (p<0.05). The TBI group did not exhibit a comparable increase in ACh release during the task. Morphological assessments revealed following TBI a significant reduction in soma area and volume in the ipsilateral nbM. In vivo sampling techniques such as microdialysis, provide increased temporal resolution and when combined with real-time behavioral performance can elucidate the correlative relationship between behaviorally-driven chemical dynamics.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Moschonas, Eleni Haritomeni | ehm18@pitt.edu | ehm18 | |
|
| ETD Committee: |
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| Date: |
11 November 2024 |
| Date Type: |
Publication |
| Defense Date: |
5 September 2024 |
| Approval Date: |
11 November 2024 |
| Submission Date: |
18 September 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
227 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Traumatic Brain Injury, Attention, Cholinergic, Acetylcholine, Microdialysis |
| Date Deposited: |
11 Nov 2024 20:37 |
| Last Modified: |
11 Nov 2024 20:37 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46976 |
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