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Curr Biol. 2015 Oct 5;25(19):2541-8. doi: 10.1016/j.cub.2015.08.022. Epub 2015 Sep 17.

Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.

Author information

1
Neuroscience Graduate Program, Vanderbilt International Scholar Program, Vanderbilt University, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA.
2
Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
3
Department of Cell and Developmental Biology, Vanderbilt University, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA.
4
Department of Physiology and Biophysics, Boston University Medical Campus, 700 Albany Street, Boston, MA 02118, USA.
5
Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. Electronic address: michael.francis@umassmed.edu.
6
Neuroscience Graduate Program, Vanderbilt International Scholar Program, Vanderbilt University, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA; Department of Cell and Developmental Biology, Vanderbilt University, 465 21(st) Avenue South, Nashville, TN 37240-7935, USA. Electronic address: david.miller@vanderbilt.edu.

Abstract

Neural circuits are actively remodeled during brain development, but the molecular mechanisms that trigger circuit refinement are poorly understood. Here, we describe a transcriptional program in C. elegans that regulates expression of an Ig domain protein, OIG-1, to control the timing of synaptic remodeling. DD GABAergic neurons reverse polarity during larval development by exchanging the locations of pre- and postsynaptic components. In newly born larvae, DDs receive cholinergic inputs in the dorsal nerve cord. These inputs are switched to the ventral side by the end of the first larval (L1) stage. VD class GABAergic neurons are generated in the late L1 and are postsynaptic to cholinergic neurons in the dorsal nerve cord but do not remodel. We investigated remodeling of the postsynaptic apparatus in DD and VD neurons using targeted expression of the acetylcholine receptor (AChR) subunit, ACR-12::GFP. We determined that OIG-1 antagonizes the relocation of ACR-12 from the dorsal side in L1 DD neurons. During the L1/L2 transition, OIG-1 is downregulated in DD neurons by the transcription factor IRX-1/Iroquois, allowing the repositioning of synaptic inputs to the ventral side. In VD class neurons, which normally do not remodel, the transcription factor UNC-55/COUP-TF turns off IRX-1, thus maintaining high levels of OIG-1 to block the removal of dorsally located ACR-12 receptors. OIG-1 is secreted from GABA neurons, but its anti-plasticity function is cell autonomous and may not require secretion. Our study provides a novel mechanism by which synaptic remodeling is set in motion through regulated expression of an Ig domain protein.

PMID:
26387713
PMCID:
PMC4596794
DOI:
10.1016/j.cub.2015.08.022
[Indexed for MEDLINE]
Free PMC Article

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