New research provides evidence that the brain’s ability to process signals and adapt to new information fluctuates rhythmically over a 24-hour cycle. A study published in Neuroscience Research reveals that while fatigue appears to suppress immediate neural activity at the end of the active phase, this same period may heighten the brain’s capacity for learning and memory formation. These findings suggest that the brain creates specific temporal windows that are optimized for different types of neural processing.
Biological systems differ significantly from mechanical circuit boards because they do not always produce the same output from the same input. An electrical circuit is hard-wired to respond consistently. A brain, however, operates within a constantly changing internal environment. Factors such as metabolism, hormonal cycles, and sleep pressure shift throughout the day and night.
“Neural circuits do not operate like fixed electronic systems,” explained study authors Yoko Ikoma and Ko Matsui, who are both professors at Tohoku University. “Even when viewing the same scene, what we perceive or remember depends strongly on our internal state at that moment. These fluctuations in responsiveness and metaplasticity are thought to arise from daily shifts in ions and neuromodulatory molecules surrounding neurons.”
“Among the factors shaping this internal environment are physiological rhythms that follow a 24-hour cycle, controlled by the interplay between the circadian clock and the external light–dark cycle. Although these rhythms are known to affect many biological processes, how they influence brain chemistry, neuronal excitability, and plasticity has remained largely unclear.”
“Our study directly examined how time of day alters neural responsiveness in the brains of nocturnal rats. These findings help explain why perception, learning, and fatigue vary across the day in both animals and humans.”
To investigate these daily rhythms, the research team focused on the primary visual cortex. They utilized a specialized technique called optogenetics. This method involves the use of transgenic rats that express a light-sensitive protein named channelrhodopsin-2 in specific neurons.
By delivering precise pulses of blue light directly to the brain, the investigators could activate these neurons without using electrical current. This allowed them to avoid the electrical interference that often complicates traditional recording methods. They implanted electrodes to record local field potentials, which are electrical signals that represent the collective activity of groups of neurons.
The study employed a sample of male Wistar rats housed under a controlled 12-hour light and 12-hour dark cycle. Since rats are nocturnal animals, their active phase occurs during the dark hours. The researchers defined “sunrise” as the end of the rat’s active period and “sunset” as the beginning of their wakefulness.
The researchers delivered identical pulses of light to the visual cortex at various times over several days. They recorded the resulting neural activity to measure excitability. The data indicated a clear diurnal pattern in how the neurons reacted.
Despite the stimulus intensity remaining constant, the neural response varied depending on the time of day. The neural signals were strongest just before sunset, which corresponds to the time when the rats were waking up and feeling refreshed. On the other hand, the signals were weakest just before sunrise, after the rats had been active all night.
This fluctuation suggests that the visual cortex is less excitable and less responsive to immediate stimuli after a prolonged period of wakefulness. To understand the chemical mechanism driving this suppression, the team investigated the role of adenosine.
Adenosine is a neuromodulator that accumulates in the brain the longer an organism stays awake. It is widely recognized as a chemical signal for sleep pressure. As adenosine levels rise, an animal feels more tired. The researchers hypothesized that high levels of adenosine at the end of the night were responsible for dampening neural activity.
To test this, they administered a drug called DPCPX to the rats. This drug acts as an antagonist to adenosine A1 receptors, effectively blocking adenosine from binding to neurons. The team administered this blocker just before sunrise and recorded the neural responses again.
When the action of adenosine was blocked, the suppression of neural activity disappeared. The signals at sunrise became as strong as they were at other times of day. This experiment provides evidence that the natural buildup of adenosine during wakefulness acts as a brake on neural excitability.
“Our results show that daily rhythms fine-tune the balance between excitability and plasticity in the cortex,” Ikoma and Matsui told PsyPost. “Because adenosine levels and sleep pressure fluctuate with circadian and behavioral cycles, the brain’s adaptability appears to be aligned with these internal rhythms. This work provides new insight into how the brain coordinates energy use, neural signaling, and learning capacity over the course of the day.”
The investigation then shifted focus to metaplasticity. This term refers to the brain’s potential to undergo changes in synaptic strength. The researchers used a different stimulation pattern consisting of rapid, repetitive light pulses to mimic a learning event.
They applied this “train stimulation” at both sunrise and sunset to see if it would induce long-term potentiation. Long-term potentiation describes a persistent strengthening of synapses that is thought to underlie memory storage. The results revealed an unexpected paradox regarding brain function and fatigue.
At sunset, when the rats were fresh and neural excitability was high, the repetitive stimulation failed to induce significant plasticity. The brain circuits remained relatively stable. However, at sunrise, when the rats were tired and excitability was low, the same stimulation triggered a robust long-term potentiation effect.
“We examined whether the brain’s metaplastic potential—the ease with which synapses can be modified—changes with time of day,” the researchers explained. “Surprisingly, repetitive optical stimulation produced LTP-like enhancement at sunrise but not at sunset. Although sleep pressure and fatigue peak at sunrise, the brain’s capacity for reorganizing its networks was greatest at this time. This suggests that metaplasticity itself follows a daily rhythm, with distinct windows that favor learning and adaptation.”
For humans, who are diurnal, these findings imply a different optimal schedule than for nocturnal rats. The equivalent of the rat’s “sunrise” is the human evening, just before sleep. This is the time when human adenosine levels are typically highest following a day of activity.
The study suggests that the human brain might be most adaptable during the twilight period approaching bedtime. While a person might feel tired and less alert in the evening, their brain could be in a prime state to consolidate new information.
“Because rats are nocturnal, sunrise corresponds to the end of their active phase and the onset of their rest period,” Ikoma and Matsui noted. “In humans, the comparable window is likely before bedtime, near sunset. Thus, these findings do not imply that learning is best immediately after waking. Rather, they indicate that the brain may enter a state more conducive to memory formation as fatigue accumulates toward the end of the active period.”
The researchers propose that the daily rhythm fine-tunes the balance between stability and flexibility in the cortex. During the start of the day, the brain is excitable and ready to react to the environment. By the end of the day, the brain shifts into a state that favors internal reorganization and memory saving.
As with all research, there are limitations to consider. The research was conducted on the visual cortex, and it is not yet clear if the same rhythms govern other areas like the hippocampus or motor cortex. “Human studies will be required to determine whether daily fluctuations in fatigue and circadian timing also modulate learning capacity,” the researchers said.
Understanding these rhythms could have practical applications for education and rehabilitation. If the brain has specific windows for adaptability, therapies involving brain stimulation or skills training could be timed to coincide with these peaks.
“In experimental animals, shifts in brain chemistry and excitability can be measured precisely across the day,” Ikoma and Matsui said. “By selectively modifying these factors, we aim to identify which components are most critical in shaping daily fluctuations in neural activity. Future studies will also incorporate various behavioral tests to determine which aspects of information processing are most sensitive to time-of-day effects.”
“In humans, determining whether comparable patterns exist could deepen our understanding of how energy metabolism, neural signaling, and learning capacity are coordinated over the day. Ultimately, these insights could guide strategies for optimizing training, rehabilitation, and cognitive performance.
The study, “Diurnal modulation of optogenetically evoked neural signals,” was authored by Yuki Donen, Yoko Ikoma, and Ko Matsui.
