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| Status |
Public on Oct 04, 2020 |
| Title |
Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network [snRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Behavioral experiences activate the Fos transcription factor (TF) in sparse populations of neurons that are critical for encoding and recalling specific events. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. Additionally, it is unknown if Fos is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-expressing hippocampal CA1 pyramidal neurons by parvalbumin (PV)-interneurons (INs) is enhanced, while perisomatic inhibition by cholecystokinin (CCK)-INs is weakened. This bidirectional modulation of inhibition is specific to Fos-expressing neurons and is abolished when the function of the Fos TF complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling, and chromatin analyses, combined with electrophysiology reveal that Fos activates the transcription of Scg2 (secretogranin II), a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As PV- and CCK-INs mediate distinct features of pyramidal cell activity, the Scg2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to CA1 theta are significantly altered with loss of Scg2. Together these findings reveal an instructive role for Fos and Scg2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition from an initially broad to a selectively modulated state. The opposing plasticity mechanisms on distinct inhibitory pathways may support the consolidation of memories over time.
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| Overall design |
We performed single-nucleus RNA-sequencing in Fos/Fosb/Junb conditional knockout mice injected with Cre- or deltaCre-GFP AAVs to study the role of AP-1 factors in activity-dependent gene expression. These mice received either AAV Cre-GFP (Cre+) or deltaCre-GFP (Cre-) injected into one hippocampal CA1 hemisphere, leaving cells in the contralateral hemisphere non-transduced as a control. Mice were subjected to 4h of KA, and CA1 nuclei were isolated and subsequently sorted using the micro-fluidic-based 10X Genomics platform.
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| Contributor(s) |
Yap E, Greenberg ME |
| Citation(s) |
33299180 |
| |
| Submission date |
Sep 30, 2020 |
| Last update date |
Jan 03, 2021 |
| Contact name |
Michael E. Greenberg |
| Organization name |
Harvard Medical School
|
| Department |
Neurobiology
|
| Lab |
Greenberg
|
| Street address |
220 Longwood Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (10)
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| GSM4811944 |
Hippocampal cells WT non-transduced control_biorep1 |
| GSM4811945 |
Hippocampal cells Cre-injected_biorep1 |
| GSM4811946 |
Hippocampal cells WT non-transduced control_biorep2 |
| GSM4811947 |
Hippocampal cells Cre-injected_biorep2 |
| GSM4811948 |
Hippocampal cells WT non-transduced control_biorep3 |
| GSM4811949 |
Hippocampal cells Cre-injected_biorep3 |
| GSM4811950 |
Hippocampal cells Uninfected control_biorep1 |
| GSM4811951 |
Hippocampal cells DeltaCre-injected_biorep1 |
| GSM4811952 |
Hippocampal cells Uninfected control_biorep2 |
| GSM4811953 |
Hippocampal cells DeltaCre-injected_biorep2 |
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| This SubSeries is part of SuperSeries: |
| GSE158843 |
Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network |
|
| Relations |
| BioProject |
PRJNA666679 |
| SRA |
SRP285941 |
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