Summary: Researchers discovered how the brain flexibly switches communication pathways depending on context, balancing between memory recall and processing new information. The mechanism depends on the interaction of slow (theta) and fast (gamma) rhythms, regulated by distinct inhibitory circuits.
In familiar environments, neurons prioritize reactivating stored memory, while in novel contexts, memory is updated with new sensory inputs. This dynamic system may also apply to attention and could help explain rhythm disruptions seen in conditions like Alzheimer’s and epilepsy.
Key Facts
- Flexible Switching: Brain rhythms shift between memory recall and novelty processing.
- Inhibitory Balance: Feedforward vs. feedback inhibition defines communication mode.
- Clinical Potential: Insights may guide new therapies for Alzheimer’s, epilepsy, and addiction.
Source: UMH
When we recall something familiar or explore a new situation, the brain does not always use the same communication routes.
An international study led by Claudio Mirasso at the Institute for Cross-Disciplinary Physics and Complex Systems (IFISC), a joint center of the Spanish National Research Council (CSIC) and the University of the Balearic Islands (UIB), and Santiago Canals at the Institute for Neurosciences (IN), a joint center of the CSIC and the Miguel Hernández University (UMH) of Elche, has discovered how the brain flexibly changes its communication pathways by modulating the balance between two fundamental inhibitory circuits.
These results, recently published in PLoS Computational Biology, show that this flexibility depends on the balance between two types of inhibitory mechanisms, which regulate the interaction between slow (theta) and fast (gamma) rhythms.
Thanks to this mechanism, the brain can select different sources of information, such as sensory stimuli from the external environment or stored sensory experience from memory.
To reach these conclusions, the researchers combined computational models with experimental recordings in the hippocampus, a brain region crucial for memory and navigation. They observed that in familiar environments, where sensory experiences are already known, neurons favor a direct communication mode that facilitates transmission from the entorhinal cortex to the hippocampus.
In this mode, the reactivation of established memory is prioritized. By contrast, when facing novelty, the brain activates another mode that integrates memory reactivation with novel sensory inputs. In this mode, memory updating is prioritized.
Until now, it was thought that the phase of slow brain rhythms organized the amplitude of faster activity; however, this study demonstrates that the relationship is bidirectional:
“This work provides a mechanistic explanation of how the brain flexibly changes communication channels depending on the context,” says Dimitrios Chalkiadakis, first author of the study.
“By adjusting the balance between different types of inhibition, circuits define which inputs to prioritize, whether from memory-related pathways or from new sensory information,” highlights the researcher.
Through a theoretical framework integrating electrophysiological data from rats exploring new and familiar environments, the experts identified two modes of operation: in one, feedforward inhibition leads to gamma-to-theta interactions, while in the other, feedback inhibition produces theta-to-gamma interactions. Neuronal circuits in the brain naturally implement both modes of inhibitory connectivity.
The study shows that the transition between them is continuous, and prioritizing one or the other depends solely on the strength of synaptic connections between neurons in the circuit. This allows the mode of operation to be flexibly adjusted to context and cognitive demands.
Beyond memory
The study suggests that this flexible form of coordination between brain rhythms could extend to other cognitive functions, such as attention. In fact, recent work in humans shows patterns consistent with the computational model. This points to a general principle of the brain: the balance between inhibitory circuits is key to directing information within its complex network of connections.
“Our results help unify opposing views on how brain rhythms of different frequencies interact”, explains Mirasso.
“Rather than being purely local or inherited from earlier regions, these rhythms emerge from the interaction between external inputs and local inhibitory dynamics. This dual mechanism enables the brain to optimize information processing under different conditions,” adds Canals.
Beyond memory and navigation, the findings could extend to other cognitive functions. Looking ahead, the researchers intend to expand their model to include a greater diversity of neuronal types and architectures specific to each brain region.
The aim is to better understand how this balance is altered in pathologies such as epilepsy, addiction, or Alzheimer’s disease: “Studying these dynamics at a mechanistic level could ultimately inspire new therapeutic intervention strategies,” both authors conclude.
Funding: This work was made possible thanks to funding from the Spanish Ministry of Science, Innovation, and Universities through the R&D Project Program (Knowledge Generation and Research Challenges) and from the Spanish State Research Agency through the Severo Ochoa Centers of Excellence and the María de Maeztu Units of Excellence Program.
About this memory and neuroscience research news
Author: Angeles Gallar
Source: UMH
Contact: Angeles Gallar – UMH
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The role of feedforward and feedback inhibition in modulating theta-gamma cross-frequency interactions in neural circuits” by Claudio Mirasso et al. PLOS Computational Biology
Abstract
The role of feedforward and feedback inhibition in modulating theta-gamma cross-frequency interactions in neural circuits
Interactions among brain rhythms play a crucial role in organizing neuronal firing sequences during specific cognitive functions. In memory formation, the coupling between the phase of the theta rhythm and the amplitude of gamma oscillations has been extensively studied in the hippocampus.
Prevailing perspectives suggest that the phase of the slower oscillation modulates the fast activity. However, recent metrics, such as Cross-Frequency Directionality (CFD), indicate that these electrophysiological interactions can be bidirectional.
Using a computational model, we demonstrate that feedforward inhibition modeled by a theta-modulated ING (Interneuron Network Gamma) mechanism induces fast-to-slow interactions, while feedback inhibition through a theta-modulated PING (Pyramidal Interneuron Network Gamma) model drives slow-to-fast interactions.
Importantly, in circuits combining both feedforward and feedback motifs, as commonly found experimentally, directionality is flexibly modulated by synaptic strength within biologically realistic ranges.
A signature of this interaction is that fast-to-slow dominance in feedforward motifs is associated with gamma oscillations of higher frequency, and vice versa.
Using previously acquired electrophysiological data from the hippocampus of rats freely navigating in a familiar environment or in a novel one, we show that CFD is dynamically regulated and linked to the frequency of the gamma band, as predicted by the model.
Finally, the model attributes each theta-gamma interaction scheme, determined by the balance between feedforward and feedback inhibition, to distinct modes of information transmission and integration, adding computational flexibility.
Our results offer a plausible neurobiological interpretation for cross-frequency directionality measurements associated with the activation of different underlying motifs that serve distinct computational needs.
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