Summary: A new study reveals that the brain’s responsiveness and capacity for learning shift with the time of day, governed by molecules like adenosine that link metabolism, sleep, and neural signaling. Using optogenetics, researchers found that identical stimuli activated brain cells differently at sunrise versus sunset, suggesting that neuronal excitability and plasticity follow daily rhythms.
These fluctuations shape when the brain is most receptive to learning, adaptation, and rehabilitation. The findings could help optimize education, therapy, and brain-stimulation timing by aligning with natural circadian cycles.
Key Facts
- Daily Neural Rhythm: Brain activity and learning potential fluctuate based on time of day.
- Adenosine’s Role: The sleep-related molecule regulates when neurons are more or less excitable.
- Learning Window: For humans, learning and memory may peak during late-day twilight hours.
Source: Tohoku University
Our brains do not react in a fixed, mechanical way like electronic circuits. Even if we see the same scene every day on our commute to work, what we feel – and whether it leaves a lasting impression – depends on our internal state at that moment. For example, your commute may be a blur if you’re too tired to pay attention to your surroundings.
The 24-hour cycle that humans naturally follow is one of the factors that shapes the brain’s internal environment. These internal physiological cycles arise from the interplay between the body’s intrinsic circadian clock and the external light-dark cycle that synchronizes it.
Yet how such daily fluctuations influence brain chemistry and affect neuronal excitability and plasticity has remained largely unknown. Now, researchers at Tohoku University have directly observed time-of-day-dependent changes in neural signal responses in the brains of nocturnal rats.
The findings were published in Neuroscience Research on October 31, 2025.
Using optogenetics, the team activated neurons in the visual cortexes of rats and recorded the resulting electrical activity. This approach allowed precise quantification of neural responsiveness. They found that identical neural stimuli evoked different responses depending on the time of day.
Neural activity was reduced at sunrise and enhanced at sunset. Since rats are nocturnal, sunrise represents the period after a night of activity when they are preparing to sleep.
To explore the underlying mechanism explaining why this was occurring, the researchers looked at adenosine, a neuromodulator that accumulates during wakefulness and makes us feel sleepy. When the researchers blocked the action of adenosine, neural activity at sunrise became disinhibited and enhanced, showing that adenosine helps regulate cortical excitability across the day.
“Neural excitability is not constant; it depends on the brain’s internal state,” says Professor Ko Matsui of Tohoku University. “Our results show that even identical neurons can respond differently depending on the time of day, governed by molecules like adenosine that link metabolism, sleep, and neuronal signaling.”
The team also examined whether the brain’s capacity for long-term potentiation (LTP), a cellular basis of learning and memory, changes with time of day. This represents the brain’s potential for metaplasticity (the brain’s ability to adjust how easily its networks change). Remarkably, repetitive optical stimulation induced LTP-like enhancement at sunrise, but not at sunset.
This was unexpected, as it suggests that although sleep pressure and fatigue peak at sunrise, the brain’s metaplastic potential is heightened at this time. These findings indicate that the brain’s ability to reorganize itself follows a daily rhythm, with specific periods more favorable for learning and adaptation.
“These results imply that our brains have temporal windows that favor adaptability,” explains lead investigator Yuki Donen.
“Knowing when the brain is most receptive to changing could help optimize training, rehabilitation, and stimulation-based therapies.”
In humans, who are mainly active during daylight hours, the capacity for learning and memory formation may peak during the twilight period approaching sunset. In other words, the best time to study or learn something new may be before bedtime.
The study reveals how daily rhythms fine-tune the balance between excitability and plasticity in the cortex. Because adenosine levels and sleep pressure follow circadian patterns, this mechanism may synchronize brain adaptability with behavioral cycles such as rest and activity.
The research provides new insight into how the brain coordinates energy use, neural signaling, and learning capacity across the day.
Key Questions Answered:
A: They found that identical neural stimuli produce different responses depending on the time of day, revealing that brain excitability follows a daily rhythm.
A: Adenosine, a molecule that builds up during wakefulness, dampens neural activity; when its action was blocked, brain activity increased, showing it helps regulate cortical excitability.
A: It suggests our brains have daily “windows” of adaptability—times when learning and memory formation may be most effective, potentially near sunset for daytime-active humans.
About this synaptic plasticity and circadian rhythm research news
Author: Public Relations
Source: Tohoku University
Contact: Public Relations – Tohoku University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Diurnal modulation of optogenetically evoked neural signals” by Ko Matsui et al. Neuroscience Research
Abstract
Diurnal modulation of optogenetically evoked neural signals
Neural signal processing in the cerebral cortex is often regarded as robust and stereotyped; however, the brain’s internal environment undergoes dynamic fluctuations across the day. Whether these diurnal rhythms modulate cortical responsiveness and plasticity remains unclear.
Here, we examined diurnal modulation of neural responsiveness and plasticity in the primary visual cortex (V1). Using transgenic rats expressing channelrhodopsin-2 (ChR2), we optically stimulated V1 neurons with brief light pulses and recorded local field potentials (LFPs) over several days.
V1 responses to single-pulse stimulation showed clear diurnal variation, with delta- and gamma-band activity modulated in a time-of-day–dependent manner.
Administration of the adenosine A1 receptor antagonist DPCPX enhanced neural responses at Zeitgeber time (ZT) 0 (Sunrise) but not at ZT 12 (Sunset).
LTP-like potentiation was observed only when train stimulation was applied at Sunrise, indicating that plasticity is also gated by diurnal phase.
These findings demonstrate that both excitability and plasticity of V1 circuits are regulated by diurnal factors.
Although it remains unclear whether these effects are driven by intrinsic circadian rhythms or light/dark-triggered mechanisms, our results highlight that cortical processing is dynamically modulated across the day, with implications for sensory function, learning, and neuromodulatory regulation.
