The role of feedforward and feedback inhibition in modulating theta-gamma cross-frequency interactions in neural circuits
Chalkiadakis, D.; Sánchez-Claros, J.; López-Madrona, V. J.; Canals, S.; Mirasso, C. R.
PLoS Computational Biology 21, e1013363 (2025)
PLoS Computational Biology 21, e1013363 (2025)
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.
Related research projects
MdM-IFISC-2
Maria de Maeztu 2023-2026
I.P.: Ernesto Estrada, Ingo Fischer, Emilio Hernández-García, Rosa Lopez, Claudio Mirasso, Jose Javier Ramasco, Raúl Toral, Roberta Zambrini
After 15 years of its existence, IFISC can point to a proven track record of impactful research. The previous 2018-2022 MdM award has significantly enhanced the institute's capabilities, as demonstrated by an …
UpMEMO
Updating the brain’s memory base: computational perspective
I.P.: Claudio Mirasso
In this project we bring together systems neuroscience (Subproject 1, IP: Santiago Canals) and computational perspectives (Subproject 2, IP: Claudio Mirasso), to investigate how hippocampal (HC) dependent episodic memories are updated to …
Notícies relacionades
Brain rhythms reveal how neural circuits flexibly route information
16 setembre de 2025
The study, published in PLoS Computational Biology, shows that the balance between feedforward and feedback inhibition determines the directionality of interactions between theta and gamma brain rhythms, enabling flexible routing of information across neural circuits.The research is the result of …
Els ritmes cerebrals revelen com els circuits neuronals encaminen la informació de manera flexible
16 setembre de 2025
L’estudi, publicat a PLoS Computational Biology, mostra que l’equilibri entre la inhibició feedforward i feedback determina la direccionalitat de les interaccions entre els ritmes cerebrals theta i gamma, i permet encaminar la informació de manera flexible a través dels circuits …
Los ritmos cerebrales revelan cómo los circuitos neuronales dirigen la información con flexibilidad
16 setembre de 2025
El estudio, publicado en PLoS Computational Biology, muestra que el equilibrio entre la inhibición feedforward y la inhibición feedback determina la direccionalidad de las interacciones entre los ritmos cerebrales theta y gamma, permitiendo un enrutamiento flexible de la información a …