Regulation of subfornical organ neurons by the cytokine interleukin-6
| dc.contributor.author | Morelli, Tessa | |
| dc.contributor.examiningcommittee | Fuat, Balci (Biological Sciences) | |
| dc.contributor.examiningcommittee | Mizuno, Tooru (Max Rady Faculty of Medicine) | |
| dc.contributor.supervisor | Fry, Mark | |
| dc.date.accessioned | 2023-08-30T19:49:05Z | |
| dc.date.available | 2023-08-30T19:49:05Z | |
| dc.date.issued | 2023-07-05 | |
| dc.date.submitted | 2023-08-15T16:37:23Z | en_US |
| dc.degree.discipline | Biological Sciences | en_US |
| dc.degree.level | Master of Science (M.Sc.) | |
| dc.description.abstract | Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of both the central nervous system and the immune system. The subfornical organ (SFO) is a sensory circumventricular organ that senses circulating signaling molecules involved in autonomic cardiovascular regulation. In our study, we examined whether IL-6 modulated electrophysiological properties of SFO neurons, and explored possible mechanisms. We prepared coronal brain slices containing SFO from male Sprague-Dawley rats and performed whole-cell patch clamp recordings on neurons. Current clamp findings revealed that application of IL-6 caused depolarisation in 37.9% of neurons (n=11; mean ± SEM, 8.8 ± 2.7 mV) and hyperpolarisation in 24.2% of neurons (n=7; -7.4 ± 1.4 mV), whereas the membrane potential of remaining neurons was unaffected (n=11; 0.3 ± 0.4 mV). These effects remained in the presence of tetrodotoxin (n=8; 62.5% depolarised, 12.5% hyperpolarised, 25% non-responders), and with both tetrodotoxin and kynurenic acid (n=8; 25% depolarised, 12.5% hyperpolarised, 62.5% non-responders), suggesting IL-6 modulates the SFO through direct post-synaptic transmission. Our study showed a decrease in input resistance with a reversal potential of effect of -76.18 ± 5.08 mV in neurons that depolarised suggesting the modulation of K+ channels in response to IL-6. Conversely, we found an increase in input resistance with a reversal potential of effect of -62.67 ± 4.87 mV in neurons that had a membrane hyperpolarisation suggesting additional modulation of a nonselective cation current. Voltage-clamp experiments found that the majority of cells that responded to IL-6 displayed the characterization of non-inactivating potassium current. Our results are consistent with previous literature that showed intravenous injection of IL-6 caused activation of SFO neurons, but our data additionally suggests that IL-6 hyperpolarises the membrane potential of an additional subset of SFO neurons through axonal projections other than the paraventricular nucleus. These results indicate that IL-6 modulates electrical properties of SFO neurons, however, the mechanisms that underly the hyperpolarisation and depolarisation need further characterization. Taken together, our study shows that IL-6 affects the excitability of SFO neurons which is important when aiming to understand inflammation caused by IL-6 release during homeostatic challenges. | |
| dc.description.note | October 2023 | |
| dc.description.sponsorship | University of Manitoba | |
| dc.identifier.uri | http://hdl.handle.net/1993/37519 | |
| dc.language.iso | eng | |
| dc.rights | open access | en_US |
| dc.subject | electrophysiology | |
| dc.subject | patch-clamp | |
| dc.subject | SFO | |
| dc.subject | IL-6 | |
| dc.title | Regulation of subfornical organ neurons by the cytokine interleukin-6 | |
| dc.type | master thesis | en_US |
| local.subject.manitoba | no | |
| oaire.awardTitle | NSERC Canada Graduate Scholarship – Master (CGS-M) | |
| oaire.awardURI | https://www.nserc-crsng.gc.ca/Students-Etudiants/Guides-Guides/TriRTA-TriBFR_eng.asp | |
| project.funder.identifier | https://doi.org/10.13039/501100000038 | |
| project.funder.name | Natural Sciences and Engineering Research Council of Canada |