Every time we walk into a room, meet a stranger, or recall the face of a loved one, our brain makes a choice. It must decide whether to rely on past experience or to integrate fresh information from the present. Remarkably, this decision does not follow a single fixed route. Instead, the brain changes its communication pathways on demand, like a vast city rerouting traffic to avoid congestion or to reach a new destination more quickly.
A recent international study led by Claudio Mirasso at the Institute for Cross-Disciplinary Physics and Complex Systems (IFISC) and Santiago Canals at the Institute for Neurosciences (IN) has uncovered how the brain accomplishes this flexibility. Their findings, published in PLoS Computational Biology, reveal that the brain achieves this adaptability by fine-tuning the balance between two powerful inhibitory circuits that regulate the way neurons communicate.
This discovery brings us closer to understanding not just how we remember, but how we think, adapt, and learn when faced with novelty.
The Rhythms of the Brain
The human brain is an orchestra of rhythms. Neurons fire in patterns that create waves of electrical activity, known as brain oscillations. These rhythms can be fast, like gamma waves that ripple dozens of times per second, or slow, like theta waves that cycle a few times each second.
Traditionally, neuroscientists believed that slower rhythms acted as conductors, setting the beat for faster activity. But the new research challenges this view. Instead, it shows that the relationship is bidirectional: fast and slow rhythms can shape each other, depending on the context and the type of inhibition dominating the circuit.
This interaction between rhythms is not just a background hum—it is the mechanism that determines whether the brain leans on memory or welcomes new sensory input.
Memory Versus Novelty
The hippocampus, a seahorse-shaped structure deep in the brain, plays a central role in memory and navigation. It is the hub where external sensory information meets stored experiences. Using computational models and experimental data from rats, the researchers showed how hippocampal circuits shift their communication style depending on whether an environment is familiar or new.
In a familiar setting, the brain takes the fast lane. Neurons favor direct communication between the entorhinal cortex—a region that processes sensory information—and the hippocampus. This mode streamlines the reactivation of established memories, allowing us to quickly recognize familiar faces or retrace well-known routes.
But in unfamiliar situations, the brain changes gears. Communication becomes more integrative, combining memory reactivation with fresh sensory inputs. This helps update memory stores with new information, essential for adapting to change or learning something new.
These two modes are not rigid categories. Instead, the brain slides smoothly between them, guided by the strength of synaptic connections and the balance of inhibitory circuits.
The Inhibitory Balance
The key to this flexibility lies in inhibition—the brain’s way of controlling and shaping neural activity. Inhibitory neurons act like gatekeepers, preventing overstimulation and guiding the flow of information.
The study identified two distinct modes of inhibition. In one, feedforward inhibition allows fast gamma activity to shape slower theta rhythms. In the other, feedback inhibition lets theta rhythms guide gamma oscillations. By shifting the balance between these modes, the brain decides which inputs to prioritize: familiar memories or new sensory experiences.
This dual mechanism explains how the same circuits can adapt to different cognitive demands without the need for entirely separate pathways. It is like a switchboard that dynamically reroutes signals depending on the situation.
Beyond Memory: A General Principle of Cognition
Although the research focused on memory and navigation, its implications reach much further. The same mechanism may underlie other cognitive functions, such as attention. Human studies already show patterns that align with the computational models, suggesting that this dynamic interplay of brain rhythms is a general principle of information processing.
By balancing different forms of inhibition, the brain can flexibly direct the flow of information within its complex network. This not only explains how we learn and remember but also unifies competing theories about how brain rhythms interact. Rather than being dictated solely by external inputs or local dynamics, rhythms emerge from the conversation between both.
Implications for Health and Disease
Understanding these mechanisms is more than a scientific triumph—it could pave the way for new medical breakthroughs. Disorders such as epilepsy, addiction, and Alzheimer’s disease involve disruptions in the brain’s inhibitory balance. By studying how healthy circuits shift between modes, researchers hope to uncover strategies to restore flexibility when it is lost.
If we can learn how to gently recalibrate the balance of inhibition, we may be able to design therapies that help the brain regain its ability to prioritize information effectively. From improving memory in dementia to refining treatments for psychiatric disorders, the possibilities are profound.
A Brain Built to Adapt
At its heart, this research tells a story about adaptability. The brain is not a rigid machine locked into fixed routes of communication. It is a living network that bends and flexes, choosing the best path for the situation at hand.
When we walk into a familiar room, it calls upon memory. When we step into unknown territory, it opens its circuits to novelty. This delicate dance between old and new, between stability and change, is what allows us to thrive in a world that is both predictable and surprising.
The study by Mirasso, Canals, and their collaborators does more than explain a neurological mechanism. It reminds us of the essence of human cognition: the ability to balance what we know with what we discover. In this balance lies our capacity to learn, to adapt, and to imagine.
More information: Dimitrios Chalkiadakis et al, The role of feedforward and feedback inhibition in modulating theta-gamma cross-frequency interactions in neural circuits, PLOS Computational Biology (2025). DOI: 10.1371/journal.pcbi.1013363
