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Neurotransmitter co-transmission: synaptic architectures, functional logic, and emerging tools.

Elif Tunc-Ozcan¹

¹Department of Neurosciences, University of New Mexico, Albuquerque, NM, United States.

Frontiers in Molecular Neuroscience

|July 3, 2026

Summary

Neurons use multiple neurotransmitters (co-transmission) for complex signaling, challenging the single-transmitter view. This versatile mechanism enhances neural circuit flexibility, precision, and context-dependence.

Keywords:

neurotransmission neurotransmitter co-release neurotransmitter co-transmission synaptic architectures synaptic plasticity

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Area of Science:

Neuroscience
Cellular Biology
Systems Neuroscience

Background:

Traditional neuroscience viewed neurons as single-transmitter systems.
Emerging evidence highlights neurotransmitter co-transmission as a fundamental principle.
Co-transmission involves complex synaptic architectures and distinct release rules.

Purpose of the Study:

To review the current understanding of neurotransmitter co-transmission.
To explore the organizational principles and functional implications of co-transmission.
To discuss challenges and future directions in studying multi-transmitter neurons.

Main Methods:

Integration of molecular profiling, electrophysiology, and high-resolution anatomy.
Utilizing optogenetics and genetically encoded neurotransmitter sensors.
Multimodal strategies to link synaptic architecture to release dynamics and circuit function.

Main Results:

Co-transmission expands signaling across multiple timescales.
It enhances target specificity and allows dynamic shifts in transmitter balance.
Distinct organizational modes impose specific rules for release and target engagement.

Conclusions:

Neurotransmitter co-transmission is a versatile mechanism enhancing neural circuit output flexibility and precision.
It challenges the canonical view of single-transmitter neurons.
Future research requires multimodal approaches to understand co-transmission in vivo.