|
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)
|
|
This SubSeries is part of SuperSeries: |
GSE158843 |
Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network |
|
Relations |
BioProject |
PRJNA666680 |
SRA |
SRP285939 |