Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS
IntroductionOverreliance on habit is linked with disorders, such as drug addiction and obsessive-compulsive disorder, and there is increasing interest in the use of repetitive transcranial magnetic stimulation (rTMS) to alter neuronal activity in the relevant pathways and for therapeutic outcomes. I...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncir.2023.1179096/full |
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| author | Maitri Tomar Maitri Tomar Jennifer Rodger Jennifer Rodger Jessica Moretti Jessica Moretti |
| author_facet | Maitri Tomar Maitri Tomar Jennifer Rodger Jennifer Rodger Jessica Moretti Jessica Moretti |
| author_sort | Maitri Tomar |
| collection | DOAJ |
| description | IntroductionOverreliance on habit is linked with disorders, such as drug addiction and obsessive-compulsive disorder, and there is increasing interest in the use of repetitive transcranial magnetic stimulation (rTMS) to alter neuronal activity in the relevant pathways and for therapeutic outcomes. In this study, we researched the brains of ephrin-A2A5−/− mice, which previously showed perseverative behavior in progressive-ratio tasks, associated with low cellular activity in the nucleus accumbens. We investigated whether rTMS treatment had altered the activity of the dorsal striatum in a way that suggested altered hierarchical recruitment of brain regions from the ventral striatum to the dorsal striatum, which is linked to abnormal habit formation.MethodsBrain sections from a limited number of mice that underwent training and performance on a progressive ratio task with and without low-intensity rTMS (LI-rTMS) were taken from a previous study. We took advantage of the previous characterization of perseverative behavior to investigate the contribution of different neuronal subtypes and striatal regions within this limited sample. Striatal regions were stained for c-Fos as a correlate of neuronal activation for DARPP32 to identify medium spiny neurons (MSNs) and for GAD67 to identify GABA-ergic interneurons.Results and discussionContrary to our hypothesis, we found that neuronal activity in ephrin-A2A5−/− mice still reflected the typical organization of goal-directed behavior. There was a significant difference in the proportion of neuronal activity across the striatum between experimental groups and control but no significant effects identifying a specific regional change. However, there was a significant group by treatment interaction which suggests that MSN activity is altered in the dorsomedial striatum and a trend suggesting that rTMS increases ephrin-A2A5−/− MSN activity in the DMS. Although preliminary and inconclusive, the analysis of this archival data suggests that investigating circuit-based changes in striatal regions may provide insight into chronic rTMS mechanisms that could be relevant to treating disorders associated with perseverative behavior. |
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| language | English |
| last_indexed | 2024-03-13T05:26:21Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Neural Circuits |
| spelling | doaj.art-5835d81161534f7b88bf16bb2e69b7ea2023-06-15T05:48:00ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102023-06-011710.3389/fncir.2023.11790961179096Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMSMaitri Tomar0Maitri Tomar1Jennifer Rodger2Jennifer Rodger3Jessica Moretti4Jessica Moretti5School of Biological Sciences, University of Western Australia, Crawley, WA, AustraliaBrain Plasticity Lab, Perron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaSchool of Biological Sciences, University of Western Australia, Crawley, WA, AustraliaBrain Plasticity Lab, Perron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaSchool of Biological Sciences, University of Western Australia, Crawley, WA, AustraliaBrain Plasticity Lab, Perron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaIntroductionOverreliance on habit is linked with disorders, such as drug addiction and obsessive-compulsive disorder, and there is increasing interest in the use of repetitive transcranial magnetic stimulation (rTMS) to alter neuronal activity in the relevant pathways and for therapeutic outcomes. In this study, we researched the brains of ephrin-A2A5−/− mice, which previously showed perseverative behavior in progressive-ratio tasks, associated with low cellular activity in the nucleus accumbens. We investigated whether rTMS treatment had altered the activity of the dorsal striatum in a way that suggested altered hierarchical recruitment of brain regions from the ventral striatum to the dorsal striatum, which is linked to abnormal habit formation.MethodsBrain sections from a limited number of mice that underwent training and performance on a progressive ratio task with and without low-intensity rTMS (LI-rTMS) were taken from a previous study. We took advantage of the previous characterization of perseverative behavior to investigate the contribution of different neuronal subtypes and striatal regions within this limited sample. Striatal regions were stained for c-Fos as a correlate of neuronal activation for DARPP32 to identify medium spiny neurons (MSNs) and for GAD67 to identify GABA-ergic interneurons.Results and discussionContrary to our hypothesis, we found that neuronal activity in ephrin-A2A5−/− mice still reflected the typical organization of goal-directed behavior. There was a significant difference in the proportion of neuronal activity across the striatum between experimental groups and control but no significant effects identifying a specific regional change. However, there was a significant group by treatment interaction which suggests that MSN activity is altered in the dorsomedial striatum and a trend suggesting that rTMS increases ephrin-A2A5−/− MSN activity in the DMS. Although preliminary and inconclusive, the analysis of this archival data suggests that investigating circuit-based changes in striatal regions may provide insight into chronic rTMS mechanisms that could be relevant to treating disorders associated with perseverative behavior.https://www.frontiersin.org/articles/10.3389/fncir.2023.1179096/fullhabit formationdorsal striatumnucleus accumbensrTMSephrinc-Fos |
| spellingShingle | Maitri Tomar Maitri Tomar Jennifer Rodger Jennifer Rodger Jessica Moretti Jessica Moretti Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS Frontiers in Neural Circuits habit formation dorsal striatum nucleus accumbens rTMS ephrin c-Fos |
| title | Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS |
| title_full | Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS |
| title_fullStr | Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS |
| title_full_unstemmed | Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS |
| title_short | Dorsal striatum c-Fos activity in perseverative ephrin-A2A5−/− mice and the cellular effect of low-intensity rTMS |
| title_sort | dorsal striatum c fos activity in perseverative ephrin a2a5 mice and the cellular effect of low intensity rtms |
| topic | habit formation dorsal striatum nucleus accumbens rTMS ephrin c-Fos |
| url | https://www.frontiersin.org/articles/10.3389/fncir.2023.1179096/full |
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