NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE158838 Query DataSets for GSE158838
Status Public on Oct 04, 2020
Title Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network [CUT&RUN]
Organism Mus musculus
Experiment type Genome binding/occupancy 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.
 
Overall design CaMK2a-Cre; lox-STOP-lox-Sun1-GFP mice were intraperitoneally injected with kainic acid (KA) or phosphate buffered saline (PBS). After 2 hours, hippocampal CA1 tissue was dissected from these mice and dounce homogenized. Nuclei were isolated from tissue homogenates and used as input for flow cytometry to isolate CaMK2a+ nuclei, marked by Sun1-GFP. CaMK2a+ nuclei were used as input for CUT&RUN to profile c-Fos binding, with CUT&RUN for IgG used as a negative control. Three biological replicates for c-Fos and IgG CUT&RUN were performed.
 
Contributor(s) Yap E, Davis CP, 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
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM4811920 CUTRUN_CA1_CaMK2a_PBS1_Fos
GSM4811921 CUTRUN_CA1_CaMK2a_PBS1_IgG
GSM4811922 CUTRUN_CA1_CaMK2a_PBS2_Fos
This SubSeries is part of SuperSeries:
GSE158843 Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network
Relations
BioProject PRJNA666680
SRA SRP285939

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE158838_RAW.tar 1.1 Gb (http)(custom) TAR (of BED, BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap