Functional Deficiency of Interneurons and Negative BOLD fMRI Response
The functional deficiency of the inhibitory system typically appears during development and can progress to psychiatric disorders or epilepsy, depending on its severity, in later years. It is known that interneurons, the major source of GABAergic inhibition in the cerebral cortex, can make direct co...
| Main Authors: | , , , , , |
|---|---|
| 格式: | 文件 |
| 语言: | English |
| 出版: |
MDPI AG
2023-03-01
|
| 丛编: | Cells |
| 主题: | |
| 在线阅读: | https://www.mdpi.com/2073-4409/12/5/811 |
| _version_ | 1827752867490955264 |
|---|---|
| author | Daniil P. Aksenov Limin Li Natalya A. Serdyukova David A. Gascoigne Evan D. Doubovikov Alexander Drobyshevsky |
| author_facet | Daniil P. Aksenov Limin Li Natalya A. Serdyukova David A. Gascoigne Evan D. Doubovikov Alexander Drobyshevsky |
| author_sort | Daniil P. Aksenov |
| collection | DOAJ |
| description | The functional deficiency of the inhibitory system typically appears during development and can progress to psychiatric disorders or epilepsy, depending on its severity, in later years. It is known that interneurons, the major source of GABAergic inhibition in the cerebral cortex, can make direct connections with arterioles and participate in the regulation of vasomotion. The goal of this study was to mimic the functional deficiency of interneurons through the use of localized microinjections of the GABA antagonist, picrotoxin, in such a concentration that it did not elicit epileptiform neuronal activity. First, we recorded the dynamics of resting-state neuronal activity in response to picrotoxin injections in the somatosensory cortex of an awake rabbit; second, we assessed the altered neuronal and hemodynamic responses to whisker stimulation using BOLD fMRI and electrophysiology recordings; third, we evaluated brain tissue oxygen levels before and after picrotoxin injection. Our results showed that neuronal activity typically increased after picrotoxin administration, the BOLD responses to stimulation became negative, and the oxygen response was nearly abolished. Vasoconstriction during the resting baseline was not observed. These results indicate that picrotoxin provoked imbalanced hemodynamics either due to increased neuronal activity, decreased vascular response, or a combination of both. |
| first_indexed | 2024-03-11T07:29:04Z |
| format | Article |
| id | doaj.art-b7d78f1a5cbf4a728d9c27f51511a529 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T07:29:04Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b7d78f1a5cbf4a728d9c27f51511a5292023-11-17T07:28:26ZengMDPI AGCells2073-44092023-03-0112581110.3390/cells12050811Functional Deficiency of Interneurons and Negative BOLD fMRI ResponseDaniil P. Aksenov0Limin Li1Natalya A. Serdyukova2David A. Gascoigne3Evan D. Doubovikov4Alexander Drobyshevsky5Department of Radiology, NorthShore University HealthSystem, Evanston, IL 60201, USADepartment of Radiology, NorthShore University HealthSystem, Evanston, IL 60201, USADepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USADepartment of Radiology, NorthShore University HealthSystem, Evanston, IL 60201, USADepartment of Radiology, NorthShore University HealthSystem, Evanston, IL 60201, USAPritzker School of Medicine, University of Chicago, Chicago, IL 60637, USAThe functional deficiency of the inhibitory system typically appears during development and can progress to psychiatric disorders or epilepsy, depending on its severity, in later years. It is known that interneurons, the major source of GABAergic inhibition in the cerebral cortex, can make direct connections with arterioles and participate in the regulation of vasomotion. The goal of this study was to mimic the functional deficiency of interneurons through the use of localized microinjections of the GABA antagonist, picrotoxin, in such a concentration that it did not elicit epileptiform neuronal activity. First, we recorded the dynamics of resting-state neuronal activity in response to picrotoxin injections in the somatosensory cortex of an awake rabbit; second, we assessed the altered neuronal and hemodynamic responses to whisker stimulation using BOLD fMRI and electrophysiology recordings; third, we evaluated brain tissue oxygen levels before and after picrotoxin injection. Our results showed that neuronal activity typically increased after picrotoxin administration, the BOLD responses to stimulation became negative, and the oxygen response was nearly abolished. Vasoconstriction during the resting baseline was not observed. These results indicate that picrotoxin provoked imbalanced hemodynamics either due to increased neuronal activity, decreased vascular response, or a combination of both.https://www.mdpi.com/2073-4409/12/5/811rabbitneurovascular couplingpicrotoxinsomatosensoryGABAexcitatory-inhibitory balance |
| spellingShingle | Daniil P. Aksenov Limin Li Natalya A. Serdyukova David A. Gascoigne Evan D. Doubovikov Alexander Drobyshevsky Functional Deficiency of Interneurons and Negative BOLD fMRI Response Cells rabbit neurovascular coupling picrotoxin somatosensory GABA excitatory-inhibitory balance |
| title | Functional Deficiency of Interneurons and Negative BOLD fMRI Response |
| title_full | Functional Deficiency of Interneurons and Negative BOLD fMRI Response |
| title_fullStr | Functional Deficiency of Interneurons and Negative BOLD fMRI Response |
| title_full_unstemmed | Functional Deficiency of Interneurons and Negative BOLD fMRI Response |
| title_short | Functional Deficiency of Interneurons and Negative BOLD fMRI Response |
| title_sort | functional deficiency of interneurons and negative bold fmri response |
| topic | rabbit neurovascular coupling picrotoxin somatosensory GABA excitatory-inhibitory balance |
| url | https://www.mdpi.com/2073-4409/12/5/811 |
| work_keys_str_mv | AT daniilpaksenov functionaldeficiencyofinterneuronsandnegativeboldfmriresponse AT liminli functionaldeficiencyofinterneuronsandnegativeboldfmriresponse AT natalyaaserdyukova functionaldeficiencyofinterneuronsandnegativeboldfmriresponse AT davidagascoigne functionaldeficiencyofinterneuronsandnegativeboldfmriresponse AT evanddoubovikov functionaldeficiencyofinterneuronsandnegativeboldfmriresponse AT alexanderdrobyshevsky functionaldeficiencyofinterneuronsandnegativeboldfmriresponse |