During brain development, neural circuits face a fundamental challenge: they must remain flexible enough to learn from experience, yet stable enough to avoid runaway excitation or functional collapse. The brain solves this problem through homeostatic plasticity, a set of mechanisms that globally adjust synaptic and intrinsic properties to keep activity within a workable range. One of its best-known forms is synaptic scaling, in which neurons strengthen or weaken many excitatory synapses in concert when overall network activity changes.
Most classic studies of synaptic scaling rely on extreme manipulations—such as complete sensory deprivation or pharmacological silencing—that rarely occur in real life. In contrast, modern environments more commonly expose developing brains to prolonged artificial lighting, screens, and extended photoperiods, rather than total darkness. This discrepancy motivated a deceptively simple but surprisingly unexplored question:
What happens to developing brain circuits when the “day” itself is stretched?
Does persistent sensory drive engage a homeostatic program that actively weakens excitatory synapses to prevent overload—and if so, how is this state established and maintained?
Stretching the day in a developing brain
To address this question, we turned to Xenopus laevis tadpoles, whose optic tectum provides a powerful in vivo system for studying experience-dependent circuit development. This brain region integrates visual input, undergoes well-defined critical periods, and is highly accessible for electrophysiology and live imaging.
During a key developmental window, we manipulated the light cycle to create three conditions:
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12LE: standard 12 h light / 12 h dark
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20LE: prolonged light, 20 h light / 4 h dark
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4LE: reduced light, 4 h light / 20 h dark
We then followed synaptic and molecular changes longitudinally, examining tadpoles after 2, 5, and 8 days of exposure.
To enhance reproducibility and better match tadpole visual sensitivity, we used green light as the primary illumination. Tadpoles are particularly responsive in this wavelength range, allowing us to elicit reliable visually driven activity under controlled illuminance. This design created a simple, ecologically relevant manipulation that closely mirrors real-world changes in visual experience.
Weaker synapses, but a resilient circuit
The results challenged a naïve “more stimulation equals stronger synapses” intuition. As expected, excitatory synaptic strength normally declines as development progresses. However, prolonged light exposure accelerated and amplified this process. Tadpoles in the 20LE condition showed reduced mEPSC amplitudes and weaker visually evoked responses—clear hallmarks of global excitatory synaptic downscaling.
Yet the circuit did not become hypoactive. Instead, intrinsic neuronal excitability increased, effectively compensating for weaker synaptic input. In other words, the system rebalanced itself: synapses were scaled down, but neurons became more ready to fire, preserving functional output. This coordinated adjustment is a textbook example of homeostatic regulation operating at the level of the intact developing brain.
From light exposure to a lasting synaptic state
A central question then emerged: how does an external environmental variable—ambient light—produce a synaptic state that lasts for days?
Our data point to a two-layered mechanism:
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Epigenetic and transcriptional priming
Prolonged light increased histone acetylation in the optic tectum. This process was regulated by class I histone deacetylases, particularly HDAC2 and HDAC3, and was associated with transcriptional changes in genes encoding AMPA receptor subunits. This layer appears to “prime” neurons for a lower excitatory set point. -
Synaptic execution and consolidation
At the synapse, Rab5c-associated endocytosis and endosomal trafficking were upregulated, promoting AMPAR internalization and stabilizing reduced excitatory transmission. This trafficking machinery acts as the executor, translating transcriptional programs into durable synaptic change.
Together, these layers provide a mechanistic bridge from sustained sensory experience to persistent synaptic downscaling—linking chromatin remodeling to membrane trafficking within a living circuit.
A reversible, adaptive program
Importantly, these changes were not permanent. When tadpoles were returned from the prolonged-light condition to a standard light cycle, synaptic transmission and AMPAR expression recovered. This reversibility distinguishes homeostatic adaptation from developmental damage and highlights the brain’s remarkable capacity to recalibrate itself when environmental conditions change.
The ability to toggle this system on and off also provides a powerful experimental framework for dissecting how epigenetic regulation and synaptic trafficking divide labor—and cooperate—during circuit maturation.
What surprised us—and what comes next
Two findings point toward especially intriguing future directions. First, reduced light exposure (4LE) produced minimal homeostatic effects, despite the fact that classical visual deprivation paradigms robustly alter synaptic scaling. This suggests that prolonged stimulation and deprivation engage fundamentally different regulatory mechanisms, an idea that remains largely unexplored.
Second, while our study focused on excitatory synapses, the balance between excitation and inhibition is central to circuit stability. How inhibitory transmission adjusts—or fails to adjust—during prolonged-light-induced scaling remains an open and fascinating question. Understanding whether inhibitory circuits follow, oppose, or independently regulate this process will be critical for a complete picture of developmental homeostasis.
By simply lengthening the day, we uncovered a coordinated, reversible program that allows developing brain circuits to remain stable in a world of persistent sensory drive. In an era of artificial lighting and extended screen exposure, understanding how the brain adapts to prolonged stimulation may be more relevant than ever.