Summary: Neurons can rapidly rebalance their communication using a structural signal rather than electrical activity, overturning long-held assumptions about how synapses maintain stability. When receptors on the receiving side of a synapse were blocked, they physically reorganized, triggering the sending neuron to increase neurotransmitter release and preserve steady signaling.
This fast correction happened even when electrical activity was silenced, showing that structural cues alone can drive homeostatic adjustments. The findings provide new insight into how the brain protects movement, learning and memory when circuits become disrupted.
Key Facts:
- Rapid Structural Trigger: Neurons stabilize communication through physical reorganization of receptors, not electrical activity.
- DLG Required: The scaffold protein DLG is essential for this fast homeostatic response.
- Disease Insight: Failures in this mechanism may contribute to conditions such as epilepsy and autism.
Source: USC
Every movement you make and every memory you form depends on precise communication between neurons. When that communication is disrupted, the brain must rapidly rebalance its internal signaling to keep circuits functioning properly.
New research from the USC Dornsife College of Letters, Arts and Sciences shows that neurons can stabilize their signaling using a fast, physical mechanism — not the electrical activity scientists long assumed was required.
The discovery, supported by grants from the National Institutes of Health and published recently in Proceedings of the National Academy of Sciences, reveals a system that doesn’t depend on the flow of charged particles to maintain signaling when part of a synapse — the junction between neurons — suddenly stops working.
Maintaining this balance between neurons is essential for muscle control, learning and overall brain health. Failure to maintain this “homeostasis” has been linked to neurological conditions such as epilepsy and autism.
USC Dornsife researchers led by Dion Dickman, professor of biological sciences, set out to understand how neurons compensate when communication between them falters. Specifically, they wanted to know how the receiving side of a synapse detects a sudden loss of function and signals the sending neuron to increase its output to restore homeostasis.
Working with fruit flies, a standard model for studying the nervous system, the team blocked glutamate receptors on the receiving side of the synapse with a chemical known to shut them down, then used electrical recordings and high-resolution microscopy to observe how the synapse responded.
To identify the molecules responsible for triggering the response, the researchers used CRISPR gene-editing tools to remove specific structural proteins one by one and observe what changed in the cells.
This process of elimination revealed that the key trigger for the rapid adjustment is not the loss of electrical activity but the physical reorganization of a specific type of receptor. When these receptors were blocked, they rearranged themselves within the synapse, which set off a signaling process that instructed the sending neuron to release more neurotransmitter, helping maintain steady communication.
A scaffold protein called DLG proved essential for this response. When DLG was removed using CRISPR, the rapid compensation failed.
The researchers also showed that this fast signaling process continues even when all electrical synapse activity is silenced, indicating that the system relies on structural cues rather than electrical signals.
Understanding how synapses quickly adapt could help guide future research into treatments that strengthen neural resilience and ward off neurological diseases.
About the study
In addition to Dickman, study researchers include first author Chengjie Qiu, Sarah Perry, Christine Chen, Jiawen Chen, Jin Zhuang, Yifu Han and Pragya Goel, all of USC Dornsife.
Funding: The study was supported by National Institutes of Health grants NS091546 and NS26654.
Key Questions Answered:
A: A structural rearrangement of receptors at the synapse triggers increased neurotransmitter release.
A: No — the response occurs even when electrical synapse activity is completely silenced.
A: It identifies a fast, non-electrical pathway that helps circuits stay stable, offering new clues for treating disorders linked to synaptic imbalance.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurotransmission research news
Author: Darrin Joy
Source: USC
Contact: Darrin Joy – USC
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Nonionic signaling rapidly remodels postsynaptic DLG to induce retrograde homeostatic plasticity” by Dion Dickman et al. PNAS
Abstract
Nonionic signaling rapidly remodels postsynaptic DLG to induce retrograde homeostatic plasticity
Neural circuits must adapt to maintain stable communication. When a postsynaptic cell’s ability to receive signals is impaired, its presynaptic partner compensates by boosting neurotransmitter release.
This study uses the Drosophila neuromuscular junction (NMJ) to reveal how this retrograde signal is transmitted: It does not rely on altered ionic flow, but rather utilizes a nonionic mechanism.
Pharmacological blockade of postsynaptic receptors triggers a rapid structural reorganization of the synapse, a physical change that initiates retrograde signaling to instruct the presynaptic neuron to increase its output. Unexpectedly, the entire process occurs independently of synaptic activity.
Uncovering this activity-independent basis for homeostatic plasticity provides a framework for understanding how neural circuits remain resilient in health and disease.
