The flexible brain: How circuit excitability and plasticity shift across the day

(Press-News.org) 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.

END