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| Status |
Public on Sep 01, 2024 |
| Title |
Activity-dependent history in hippocampal neurons dictates temporal dynamics of homeostatic synaptic scaling |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Neural circuits utilize a host of homeostatic plasticity mechanisms, including synaptic scaling, to maintain stability in circuits undergoing experience-dependent remodeling necessary for information processing. During synaptic scaling, compensatory adaptations in synaptic strength are induced after chronic manipulations in neuronal firing, but our understanding of this process is largely limited to its initial induction. How these homeostatic synaptic adaptations evolve when activity renormalizes and their impact on subsequent homeostatic compensation are both poorly understood. To examine these issues, we investigated whether a previous history of homeostatic scaling in networks of cultured hippocampal neurons altered their subsequent homeostatic responses to chronic activity manipulations. Unexpectedly, we found that a history of synaptic scaling strongly suppressed future scaling to the same, and even opposite, activity challenges. This history-dependent suppression was specific for future homeostatic compensation, as networks with a prior scaling history showed no deficits in the chemical induction of long-term potentiation (cLTP), a Hebbian form of synaptic plasticity. Hippocampal neurons with a prior scaling history exhibited normal engagement of activity-dependent signaling during subsequent activity challenges (as assessed by examination of the ERK/MAPK pathway) but demonstrated widespread alterations in activity-dependent transcriptional
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| Overall design |
To examine transcriptional dynamics directly, we employed bromouridine RNA sequencing (BrU-seq) to monitor newly generated transcripts over the first 4hrs of activity silencing. This genome-wide nascent transcript profiling technique provides an unbiased account of newly transcribed genes during TTX silencing of neurons. We prepared primary hippocampal and cortical neuron co-cultures from brain tissue isolated from P1-P2 rats and allowed them to mature for 14 days in vitro (DIV). We adopted the same paradigm we have used in functional studies, where neurons are treated with either vehicle or TTX from 0-24hrs, followed by a 48hr washout period, then either vehicle or TTX again for 4hrs. During the last 30mins of this second TTX treatment, we added BrU to the culture medium to label newly synthesized transcripts which are then isolated using magnetic beads coated with anti-BrU antibody and processed for next-generation sequencing.
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| Contributor(s) |
Chen A, Garay P, Iwase S, Sutton M |
| Citation missing |
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| Submission date |
Jul 28, 2021 |
| Last update date |
Sep 01, 2024 |
| Contact name |
Shigeki Iwase |
| E-mail(s) |
siwase@umich.edu
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| Organization name |
University of Michigan
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| Street address |
1241 E. Catherine St.
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| City |
Ann Arbor |
| ZIP/Postal code |
48108 |
| Country |
USA |
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| Platforms (1) |
| GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA750328 |
| SRA |
SRP330195 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180993_SELECTED_SUTTON_BRUSEQ_JULY2018.txt.gz |
268.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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