Structural Remodeling of Active Zones Is Associated with Synaptic Homeostasis.
J Neurosci
; 40(14): 2817-2827, 2020 04 01.
Article
in En
| MEDLINE
| ID: mdl-32122953
ABSTRACT
Perturbations to postsynaptic glutamate receptors (GluRs) trigger retrograde signaling to precisely increase presynaptic neurotransmitter release, maintaining stable levels of synaptic strength, a process referred to as homeostatic regulation. However, the structural change of homeostatic regulation remains poorly defined. At wild-type Drosophila neuromuscular junction synapse, there is one Bruchpilot (Brp) ring detected by superresolution microscopy at active zones (AZs). In the present study, we report multiple Brp rings (i.e., multiple T-bars seen by electron microscopy) at AZs of both male and female larvae when GluRs are reduced. At GluRIIC-deficient neuromuscular junctions, quantal size was reduced but quantal content was increased, indicative of homeostatic presynaptic potentiation. Consistently, multiple Brp rings at AZs were observed in the two classic synaptic homeostasis models (i.e., GluRIIA mutant and pharmacological blockade of GluRIIA activity). Furthermore, postsynaptic overexpression of the cell adhesion protein Neuroligin 1 partially rescued multiple Brp rings phenotype. Our study thus supports that the formation of multiple Brp rings at AZs might be a structural basis for synaptic homeostasis.SIGNIFICANCE STATEMENT Synaptic homeostasis is a conserved fundamental mechanism to maintain efficient neurotransmission of neural networks. Active zones (AZs) are characterized by an electron-dense cytomatrix, which is largely composed of Bruchpilot (Brp) at the Drosophila neuromuscular junction synapses. It is not clear how the structure of AZs changes during homeostatic regulation. To address this question, we examined the structure of AZs by superresolution microscopy and electron microscopy during homeostatic regulation. Our results reveal multiple Brp rings at AZs of glutamate receptor-deficient neuromuscular junction synapses compared with single Brp ring at AZs in wild type (WT). We further show that Neuroligin 1-mediated retrograde signaling regulates multiple Brp ring formation at glutamate receptor-deficient synapses. This study thus reveals a regulatory mechanism for synaptic homeostasis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synapses
/
Synaptic Transmission
/
Homeostasis
/
Neuromuscular Junction
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Neurosci
Year:
2020
Document type:
Article
Affiliation country: