Eilif Benjamin Muller

Assemblies, synapse clustering, and network topology interact with plasticity to explain structure-function relationships of the cortical connectome

András Ecker

Daniela Egas Santander

Marwan Abdellah

Jorge Blanco Alonso

Sirio Bolaños-Puchet

Giuseppe Chindemi

Dhuruva Priyan Gowri Mariyappan

James B. Isbister

James King

Pramod Kumbhar

Ioannis Magkanaris

Eilif Benjamin Muller

Michael W. Reimann

Synaptic plasticity underlies the brain’s ability to learn and adapt. While experiments in brain slices have revealed mechanisms and proto… (voir plus)cols for the induction of plasticity between pairs of neurons, how these synaptic changes are coordinated in biological neuronal networks to ensure the emergence of learning remains poorly understood. Simulation and modeling have emerged as important tools to study learning in plastic networks, but have yet to achieve a scale that incorporates realistic network structure, active dendrites, and multi-synapse interactions, key determinants of synaptic plasticity. To rise to this challenge, we endowed an existing large-scale cortical network model, incorporating data-constrained dendritic processing and multi-synaptic connections, with a calcium-based model of functional plasticity that captures the diversity of excitatory connections extrapolated to in vivo-like conditions. This allowed us to study how dendrites and network structure interact with plasticity to shape stimulus representations at the microcircuit level. In our exploratory simulations, plasticity acted sparsely and specifically, firing rates and weight distributions remained stable without additional homeostatic mechanisms. At the circuit level, we found plasticity was driven by co-firing stimulus-evoked functional assemblies, spatial clustering of synapses on dendrites, and the topology of the network connectivity. As a result of the plastic changes, the network became more reliable with more stimulus-specific responses. We confirmed our testable predictions in the MICrONS datasets, an openly available electron microscopic reconstruction of a large volume of cortical tissue. Our results quantify at a large scale how the dendritic architecture and higher-order structure of cortical microcircuits play a central role in functional plasticity and provide a foundation for elucidating their role in learning.

2025-07-03

eLife (publié)

doi.org

Learning to combine top-down context and feed-forward representations under ambiguity with apical and basal dendrites

Nizar Islah

Guillaume Etter

Mashbayar Tugsbayar

Busra Tugce Gurbuz

Blake Richards

Eilif Benjamin Muller

2025-06-23

Cerebral Cortex (New York, NY) (publié)

doi.org

arxiv.org

Top-down feedback matters: Functional impact of brainlike connectivity motifs on audiovisual integration

Mashbayar Tugsbayar

Mingze Li

Eilif Benjamin Muller

Blake Richards

Artificial neural networks (ANNs) are an important tool for studying neural computation, but many features of the brain are not captured by … (voir plus)standard ANN architectures. One notable missing feature in most ANN models is top-down feedback, i.e. projections from higher-order layers to lower-order layers in the network. Top-down feedback is ubiquitous in the brain, and it has a unique modulatory impact on activity in neocortical pyramidal neurons. However, we still do not understand its computational role. Here we develop a deep neural network model that captures the core functional properties of top-down feedback in the neocortex, allowing us to construct hierarchical recurrent ANN models that more closely reflect the architecture of the brain. We use this to explore the impact of different hierarchical recurrent architectures on an audiovisual integration task. We find that certain hierarchies, namely those that mimic the architecture of the human brain, impart ANN models with a light visual bias similar to that seen in humans. This bias does not impair performance on the audiovisual tasks. The results further suggest that different configurations of top-down feedback make otherwise identically connected models functionally distinct from each other, and from traditional feedforward-only models. Altogether our findings demonstrate that modulatory top-down feedback is a computationally relevant feature of biological brains, and that incorporating it into ANNs can affect their behavior and helps to determine the solutions that the network can discover.

2025-01-08

bioRxiv (prépublication)

doi.org

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

James B. Isbister

András Ecker

Christoph Pokorny

Sirio Bolaños-Puchet

Daniela Egas Santander

Alexis Arnaudon

Omar Awile

Natali Barros-Zulaica

Jorge Blanco Alonso

Elvis Boci

Giuseppe Chindemi

Jean-Denis Courcol

Tanguy Damart

Thomas Delemontex

Alexander Dietz

Gianluca Ficarelli

Michael Gevaert

Joni Herttuainen

Genrich Ivaska

Weina Ji … (voir 22 de plus)

Daniel Keller

James King

Pramod Kumbhar

Samuel Lapere

Polina Litvak

Darshan Mandge

Eilif Benjamin Muller

Fernando Pereira

Judit Planas

Rajnish Ranjan

Maria Reva

Armando Romani

Christian Rössert

Felix Schürmann

Vishal Sood

Aleksandra Teska

Anil Tuncel

Werner Van Geit

Matthias Wolf

Henry Markram

Srikanth Ramaswamy

Michael W. Reimann

Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which are challenging to study in vivo… (voir plus). Large-scale, biophysically detailed models offer a tool which can complement laboratory approaches. We present a model comprising eight somatosensory cortex subregions, 4.2 million morphological and electrically-detailed neurons, and 13.2 billion local and mid-range synapses. In silico tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. The model reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, how cortical activity is shaped by high-dimensional connectivity motifs in local and mid-range connectivity, and spatial targeting rules by inhibitory subpopulations. The latter was facilitated using a rewired connectome which included specific targeting rules observed for different inhibitory neuron types in electron microscopy. The model also predicted the role of inhibitory interneuron types and different layers in stimulus encoding. Simulation tools and a large subvolume of the model are made available to enable further community-driven improvement, validation and investigation.

2024-12-13

bioRxiv (prépublication)

doi.org

Specific inhibition and disinhibition in the higher-order structure of a cortical connectome

Michael W. Reimann

Daniela Egas Santander

András Ecker

Eilif Benjamin Muller

Neuronal network activity is thought to be structured around the activation of assemblies, or low-dimensional manifolds describing states of… (voir plus) activity. Both views describe neurons acting not independently, but in concert, likely facilitated by strong recurrent excitation between them. The role of inhibition in these frameworks – if considered at all – is often reduced to blanket inhibition with no specificity with respect to which excitatory neurons are targeted. We analyzed the structure of excitation and inhibition in the MICrONS 1mm3 dataset, an electron microscopic reconstruction of a piece of cortical tissue. We found that excitation was structured around a feed-forward flow in non-random motifs of seven or more neurons. This revealed a structure of information flow from a small number of sources to a larger number of potential targets that became only visible when larger motifs were considered instead of individual pairs. Inhibitory neurons targeted and were targeted by neurons in specific sequential positions of these motifs. Additionally, disynaptic inhibition was strongest between target motifs excited by the same group of source neurons, implying competition between them. The structure of this inhibition was also highly specific and symmetrical, contradicting the idea of non-specific blanket inhibition. None of these trends are detectable in only pairwise connectivity, demonstrating that inhibition is specifically structured by these large motifs. Further, we found that these motifs represent higher order connectivity patterns which are present, but to a lesser extent in a recently released, detailed computational model, and not at all in a distance-dependent control. These findings have important implications for how synaptic plasticity reorganizes neocortical connectivity to implement learning and for the specific role of inhibition in this process.

2024-11-11

Cerebral Cortex (New York, NY) (publié)

doi.org

Community-based reconstruction and simulation of a full-scale model of the rat hippocampus CA1 region

Armando Romani

Alberto Antonietti

Davide Bella

Julian Budd

Elisabetta Giacalone

Kerem Kurban

Sára Sáray

Marwan Abdellah

Alexis Arnaudon

Elvis Boci

Cristina Colangelo

Jean-Denis Courcol

Thomas Delemontex

András Ecker

Joanne Falck

Cyrille Favreau

Michael Gevaert

Juan B. Hernando

Joni Herttuainen

Genrich Ivaska … (voir 28 de plus)

Lida Kanari

Anna-Kristin Kaufmann

James King

Pramod Kumbhar

Sigrun Lange

Huanxiang Lu

Carmen Alina Lupascu

Rosanna Migliore

Fabien Petitjean

Judit Planas

Pranav Rai

Srikanth Ramaswamy

Michael W. Reimann

Juan Luis Riquelme

Nadir Román Guerrero

Ying Shi

Vishal Sood

Mohameth François Sy

Werner Van Geit

Liesbeth Vanherpe

Tamás F. Freund

Audrey Mercer

Eilif Benjamin Muller

Felix Schürmann

Alex M. Thomson

Michele Migliore

Szabolcs Káli

Henry Markram

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive fun… (voir plus)ctions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

2024-11-01

PLoS Biology (publié)

doi.org

Community-based reconstruction and simulation of a full-scale model of the rat hippocampus CA1 region

Armando Romani

A. Antonietti

Davide Bella

Julian Budd

Elisabetta Giacalone

Kerem Kurban

Sára Sáray

Marwan Abdellah

Alexis Arnaudon

Elvis Boci

Cristina Colangelo

Jean-Denis Courcol

Thomas Delemontex

András Ecker

Joanne Falck

Cyrille Favreau

Michael Gevaert

Juan B. Hernando

Joni Herttuainen

Genrich Ivaska … (voir 28 de plus)

Lida Kanari

Anna-Kristin Kaufmann

James King

Pramod Kumbhar

Sigrun Lange

Huanxiang Lu

Carmen Alina Lupascu

Rosanna Migliore

Fabien Petitjean

Judit Planas

Pranav Rai

Srikanth Ramaswamy

Michael W. Reimann

Juan Luis Riquelme

Nadir Román Guerrero

Ying Shi

Vishal Sood

Mohameth François Sy

Werner Van Geit

Liesbeth Vanherpe

Tamás F. Freund

Audrey Mercer

Eilif Benjamin Muller

Felix Schürmann

Alex M. Thomson

Michele Migliore

Szabolcs Káli

Henry Markram

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive fun… (voir plus)ctions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

2024-11-01

PLoS Biology (publié)

doi.org

GitChameleon: Unmasking the Version-Switching Capabilities of Code Generation Models

Nizar Islah

Justine Gehring

Diganta Misra

Eilif Benjamin Muller

Irina Rish

Terry Yue Zhuo

Massimo Caccia

2024-11-01

arXiv (publié)

doi.org

arxiv.org

Seq-JEPA: Autoregressive Predictive Learning of Invariant-Equivariant World Models

Hafez Ghaemi

Eilif Benjamin Muller

Shahab Bakhtiari

Joint-embedding predictive architecture (JEPA) is a self-supervised learning (SSL) paradigm with the capacity of world modeling via action-c… (voir plus)onditioned prediction. Previously, JEPA world models have been shown to learn action-invariant or action-equivariant representations by predicting one view of an image from another. Unlike JEPA and similar SSL paradigms, animals, including humans, learn to recognize new objects through a sequence of active interactions. To introduce \emph{sequential} interactions, we propose \textit{seq-JEPA}, a novel SSL world model equipped with an autoregressive memory module. Seq-JEPA aggregates a sequence of action-conditioned observations to produce a global representation of them. This global representation, conditioned on the next action, is used to predict the latent representation of the next observation. We empirically show the advantages of this sequence of action-conditioned observations and examine our sequential modeling paradigm in two settings: (1) \emph{predictive learning across saccades}; a method inspired by the role of eye movements in embodied vision. This approach learns self-supervised image representations by processing a sequence of low-resolution visual patches sampled from image saliencies, without any hand-crafted data augmentations. (2) \emph{invariance-equivariance trade-off}; seq-JEPA's architecture results in automatic separation of invariant and equivariant representations, with the aggregated autoregressor outputs being mostly action-invariant and the encoder output being equivariant. This is in contrast with many equivariant SSL methods that expect a single representational space to contain both invariant and equivariant features, potentially creating a trade-off between the two. Empirically, seq-JEPA achieves competitive performance on both invariance and equivariance-related benchmarks compared to existing methods. Importantly, both invariance and equivariance-related downstream performances increase as the number of available observations increases.

2024-10-13

NeurIPS.cc/2024/Workshop/SSL (publié)

openreview.net

Seq-JEPA: Autoregressive Predictive Learning of Invariant-Equivariant World Models

Hafez Ghaemi

Eilif Benjamin Muller

Shahab Bakhtiari

Joint-embedding predictive architecture (JEPA) is a self-supervised learning (SSL) paradigm with the capacity of world modeling via action-c… (voir plus)onditioned prediction. Previously, JEPA world models have been shown to learn action-invariant or action-equivariant representations by predicting one view of an image from another. Unlike JEPA and similar SSL paradigms, animals, including humans, learn to recognize new objects through a sequence of active interactions. To introduce \emph{sequential} interactions, we propose \textit{seq-JEPA}, a novel SSL world model equipped with an autoregressive memory module. Seq-JEPA aggregates a sequence of action-conditioned observations to produce a global representation of them. This global representation, conditioned on the next action, is used to predict the latent representation of the next observation. We empirically show the advantages of this sequence of action-conditioned observations and examine our sequential modeling paradigm in two settings: (1) \emph{predictive learning across saccades}; a method inspired by the role of eye movements in embodied vision. This approach learns self-supervised image representations by processing a sequence of low-resolution visual patches sampled from image saliencies, without any hand-crafted data augmentations. (2) \emph{invariance-equivariance trade-off}; seq-JEPA's architecture results in automatic separation of invariant and equivariant representations, with the aggregated autoregressor outputs being mostly action-invariant and the encoder output being equivariant. This is in contrast with many equivariant SSL methods that expect a single representational space to contain both invariant and equivariant features, potentially creating a trade-off between the two. Empirically, seq-JEPA achieves competitive performance on both invariance and equivariance-related benchmarks compared to existing methods. Importantly, both invariance and equivariance-related downstream performances increase as the number of available observations increases.

2024-10-13

NeurIPS.cc/2024/Workshop/SSL (publié)

doi.org

openreview.net

Top-down feedback matters: Functional impact of brainlike connectivity motifs on audiovisual integration

Mashbayar Tugsbayar

Mingze Li

Eilif Benjamin Muller

Blake Richards

2024-10-03

bioRxiv (prépublication)

doi.org