Summary: Why does motor coordination continue to improve well into adulthood, even though the brain’s motor circuits appear fully developed by early adolescence? A new study has found the missing link: astrocytes. These star-shaped “support” cells undergo a critical transition during late adolescence, taking over the regulation of inhibitory signaling (GABA) in the cerebellum.
By shifting from neuron-driven to astrocyte-driven “tonic inhibition,” the brain allows different muscle groups to operate more independently. This “cellular handoff” is what finally enables the complex, flexible, and precise movements—like athletic agility or fine craftsmanship—that define adult physical capability.
Key Facts
- The Adolescent Shift: In early adolescence, motor inhibition is driven by neurons; by adulthood, astrocytes take over as the primary source of GABA through Best1 channels.
- Increased Independence: This astrocyte-driven signaling reduces “interference” between different groups of neurons, allowing the brain to coordinate separate body parts with much higher precision.
- The “Tonic” Background: Unlike quick bursts of signaling, astrocytes provide “tonic inhibition”—a persistent, always-on background signal that stabilizes the entire motor network.
- Best1 Gene Link: Mice lacking the Best1 gene failed to develop advanced motor coordination, remaining “stuck” with the simpler, more rigid movement patterns of younger animals.
- New Perspective: This study shifts the focus of brain development from a neuron-only model to a “neuron-astrocyte interaction” model, opening new doors for treating motor disorders and designing robotics.
Source: Institute for Basic Science
A new study reveals that astrocytes—star-shaped support cells traditionally viewed as passive partners of neurons—play a previously underappreciated role in the maturation of coordinated movement.
A research team led by Director C. Justin LEE and Senior Research Fellow HONG Sungho of the Center for Memory and Glioscience within the Institute for Basic Science (IBS), in collaboration with Professor Erik DE SCHUTTER from the Compational Neuroscience Unit at the Okinawa Institute of Science and Technology (OIST), Japan, has uncovered how astrocytes regulate inhibitory signaling in the cerebellum during development, enabling the emergence of flexible and precise motor coordination.
Motor coordination allows animals and humans to combine movements of different body parts in a flexible manner, especially when navigating complex or changing environments. Although this ability continues to improve throughout development and typically reaches its peak in adulthood, the neural circuits responsible for coordination—particularly those in the cerebellum—are thought to reach structural maturity relatively early in life. This discrepancy has long raised an unresolved question: why does motor coordination continue to improve after cerebellar circuits appear fully developed?
To investigate this puzzle, the researchers examined cerebellar granule cells, which represent one of the most abundant neuron populations in the brain. These cells are regulated by tonic inhibition, a persistent “always-on” form of inhibitory signaling mediated by the neurotransmitter GABA. Unlike transient synaptic inhibition, tonic inhibition provides a continuous regulatory background that stabilizes neuronal excitability and supports reliable information processing.
Using electrophysiological recordings, the team measured tonic inhibitory currents in granule cells from young mice (3-4 weeks old) and adult mice (8-12 weeks old). Surprisingly, the overall strength of tonic inhibition remained largely unchanged between the two age groups. However, a closer analysis revealed a major shift in the source of the inhibitory signal.
In younger animals, tonic inhibition was primarily generated by GABA released from inhibitory neurons, which diffuses beyond synaptic sites and accumulates in the surrounding extracellular space. In contrast, in adult animals the dominant source of tonic inhibition became astrocyte-derived GABA, released through Bestrophin-1 (Best1) channels.
Further experiments showed that this transition is closely associated with changes in GABA transport dynamics. In adult mice, the activity of GABA transporters (GATs)—proteins responsible for removing GABA from the extracellular space—increases substantially.
This enhanced clearance reduces the effectiveness of neuron-derived spillover GABA, thereby shifting the balance toward astrocytes, which continuously supply GABA independently of synaptic activity.
To explore how this cellular transition influences information processing at the circuit level, the researchers constructed a large-scale computational model of the cerebellar neural network comprising approximately one million neurons, incorporating physiological data from their experiments.
Professor De Schutter explains: “Our simulations indicated that when tonic inhibition becomes increasingly astrocyte-driven, interactions between granule cell populations responding to different inputs become weaker. As a result, individual granule cell groups are able to process incoming signals more independently.”
Senior Research Fellow HONG Sungho, whose work on the topic began at OIST, adds: “This shift in network dynamics could provide a neural mechanism for more flexible motor coordination. As different groups of neurons representing movements of separate body parts interfere less with each other, the brain can more easily combine multiple movement strategies—such as switching between hopping, walking, or turning—to accomplish the same behavioral goal.”
The researchers then tested these predictions experimentally using a deep learning-based behavioral analysis system capable of reconstructing mouse posture in three dimensions during spontaneous movement. Adult mice exhibited a wider variety of limb coordination patterns compared with younger animals. However, this increased diversity of movement was absent in adult mice lacking the Best1 gene, which disrupts astrocyte-mediated tonic inhibition.
Detailed analysis revealed that both young mice and adult Best1-knockout mice showed more tightly coupled limb movements, indicating reduced independence between different body parts during locomotion. These findings confirm that astrocyte-driven tonic inhibition is a critical factor in the late-stage maturation of flexible motor coordination.
Director C. Justin LEE said, “This study expands the conventional neuron-centric understanding of brain development to encompass the perspective of neuron-astrocyte interactions,” and added, “A deeper understanding of astrocyte function could inform not only research into developmental and degenerative motor disorders, but also the design of movement control systems for robotics and physical AI inspired by brain principles.”
Key Questions Answered:
A: Because your “star cells” (astrocytes) have finally taken the wheel! During late adolescence, these cells start releasing a steady stream of a chemical called GABA. This acts like “noise-canceling headphones” for your motor circuits, letting different parts of your body move independently without getting their signals crossed.
A: Your movements stay “rigid.” The study found that without this astrocyte transition, adult mice moved like clumsy youngsters—their limbs were too tightly coupled, and they couldn’t switch between different types of movement (like walking vs. turning) as easily.
A: Potentially! Current AI and robotics often focus on “neurons” (processing units). By incorporating an “astrocyte” layer—a system that provides steady, background stabilization—engineers might be able to create robots with the same fluid, adaptive grace as a human athlete.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience research news
Author: William Suh
Source: Institute for Basic Science
Contact: William Suh – Institute for Basic Science
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Cerebellar tonic inhibition orchestrates the maturation ofinformation processing and motor coordination” by Jea Kwon, Sunpil Kim, Junsung Woo, Keiko Tanaka-Yamamoto, Oliver James, Erik De Schutter, Sungho Hong & C. Justin Lee. Experimental & Molecular Medicine
DOI:10.1038/s12276-026-01657-8
Abstract
Cerebellar tonic inhibition orchestrates the maturation ofinformation processing and motor coordination
Tonic inhibition in cerebellar granule cells is crucial for maintaining information coding fidelity during motor coordination. It arises through both activity-dependent and activity-independent mechanisms, and the interplay between these mechanisms changes with age.
However, specific molecular and cellular mechanisms and how their change affects network-level computation and motor behavior remain unclear.
Here we show that, while net tonic inhibitory current remains unchanged, the main source of tonic γ-aminobutyric acid switches from synaptic spillover (neuronal activity dependent) to astrocytic Best1 (activity independent) throughout adolescence (4–8 weeks) in mice.
Computational modeling based on experimental data demonstrated that this switch downregulates the internally generated network activity mediating mutual inhibition between granule cell clusters receiving different inputs, thereby enhancing their independence.
Consistent with simulations, three-dimensional posture analysis revealed an age-dependent increase in independent limb movements during spontaneous motion, which was impaired in Best1-knockout mice.
Our findings highlight the late-stage development of complex motor coordination driven by the emergence of astrocyte-mediated tonic inhibition.
