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Single Cell Multiplex Reverse Transcription Polymerase Chain Reaction After Patch-clamp

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Published on: June 20, 2018

Genomic Decoding of Neuronal Depolarization by Stimulus-Specific NPAS4 Heterodimers.

G Stefano Brigidi¹, Michael G B Hayes², Nathaniel P Delos Santos³

¹Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0634, USA.

|October 5, 2019

Summary

This summary is machine-generated.

Neurons use distinct pathways to express the NPAS4 transcription factor in response to different electrical activities. This allows for tailored gene regulation based on action potentials (APs) and excitatory postsynaptic potentials (EPSPs).

Keywords:

ARNT ARNT2 CRISPR Cas9 NPAS4 dendrite genome hippocampus immediate early gene inducible transcription factor local translation

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Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

Cells regulate gene expression via inducible transcription factors (ITFs) in response to stimuli.
Neuronal depolarization, from action potentials (APs) and excitatory postsynaptic potentials (EPSPs), drives gene expression.
The distinct roles of APs and EPSPs in ITF-mediated genomic regulation remain unclear.

Purpose of the Study:

To investigate if distinct neuronal electrical activities are translated into specific genomic regulation modes by ITFs.
To elucidate the mechanisms by which NPAS4 expression is differentially regulated by APs and EPSPs.

Main Methods:

Utilized mouse hippocampal neurons.
Investigated spatially segregated and molecularly distinct induction mechanisms for NPAS4.
Analyzed stimulus-specific NPAS4 heterodimer formation and DNA binding patterns.

Main Results:

Action potentials and excitatory postsynaptic potentials trigger separate pathways for NPAS4 induction in hippocampal neurons.
These pathways lead to the formation of distinct NPAS4 heterodimers.
These heterodimers exhibit differential DNA binding, indicating stimulus-specific genomic regulation.

Conclusions:

NPAS4 differentially communicates neuronal spiking output and synaptic input to the nucleus.
This differential signaling enables gene regulation to be tailored to specific depolarizing activity types.
The somato-dendritic axis plays a role in activity-dependent gene expression regulation.