Pyramidal cell activity levels affect the polarity of activity-induced gene transcription changes in interneurons Article Swipe
R. Ryley Parrish
,
Neela K. Codadu
,
Claudia Racca
,
Andrew J. Trevelyan
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1152/jn.00287.2018
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1152/jn.00287.2018
Changes in gene expression are an important mechanism by which activity levels are regulated in the nervous system. It is not known, however, how network activity influences gene expression in interneurons; since they themselves provide negative feedback in the form of synaptic inhibition, there exists a potential conflict between their cellular homeostatic tendencies and those of the network. We present a means of examining this issue, utilizing simple in vitro models showing different patterns of intense network activity. We found that the degree of concurrent pyramidal activation changed the polarity of the induced gene transcription. When pyramidal cells were quiescent, interneuronal activation led to an upregulation of glutamate decarboxylase 1 ( GAD1) and parvalbumin ( Pvalb) gene transcriptions, mediated by activation of the Ras/extracellular signal-related kinase mitogen-activated protein kinase (Ras/ERK MAPK) pathway. In contrast, coactivation of pyramidal cells led to an ionotropic glutamate receptor N-methyl-d-aspartate 2B-dependent decrease in transcription. Our results demonstrate a hitherto unrecognized complexity in how activity-dependent gene expression changes are manifest in cortical networks. NEW & NOTEWORTHY We demonstrate a novel feedback mechanism in cortical networks, by which glutamatergic drive, mediated through the Ras/ERK MAPK pathway, regulates gene transcription in interneurons. Using a unique feature of certain in vitro epilepsy models, we show that without this glutamatergic feedback, intense activation of interneurons causes parvalbumin and glutamate decarboxylase 1 mRNA expression to increase. If, on the other hand, pyramidal cells are coactivated with interneurons, this leads to a downregulation of these genes.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1152/jn.00287.2018
- https://journals.physiology.org/doi/pdf/10.1152/jn.00287.2018
- OA Status
- hybrid
- Cited By
- 15
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2885963964
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2885963964Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1152/jn.00287.2018Digital Object Identifier
- Title
-
Pyramidal cell activity levels affect the polarity of activity-induced gene transcription changes in interneuronsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-08-15Full publication date if available
- Authors
-
R. Ryley Parrish, Neela K. Codadu, Claudia Racca, Andrew J. TrevelyanList of authors in order
- Landing page
-
https://doi.org/10.1152/jn.00287.2018Publisher landing page
- PDF URL
-
https://journals.physiology.org/doi/pdf/10.1152/jn.00287.2018Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://journals.physiology.org/doi/pdf/10.1152/jn.00287.2018Direct OA link when available
- Concepts
-
Glutamatergic, Parvalbumin, Biology, Cell biology, Neuroscience, MAPK/ERK pathway, Interneuron, Glutamate receptor, Glutamate decarboxylase, Signal transduction, Inhibitory postsynaptic potential, Receptor, Genetics, Biochemistry, EnzymeTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
15Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2024: 1, 2023: 2, 2022: 1, 2020: 3Per-year citation counts (last 5 years)
- References (count)
-
43Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.interneurons. | 193 |
| abstract_inverted_index.interneurons; | 30 |
| abstract_inverted_index.transcription | 191 |
| abstract_inverted_index.downregulation | 240 |
| abstract_inverted_index.signal-related | 124 |
| abstract_inverted_index.transcription. | 94, 148 |
| abstract_inverted_index.transcriptions, | 117 |
| abstract_inverted_index.Ras/extracellular | 123 |
| abstract_inverted_index.mitogen-activated | 126 |
| abstract_inverted_index.activity-dependent | 158 |
| abstract_inverted_index.N-methyl-d-aspartate | 144 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5056097437 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 4 |
| corresponding_institution_ids | https://openalex.org/I78577930, https://openalex.org/I84884186 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5099999904632568 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.74025116 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |