Biology subjects

Larrat, B.

Publications and source records attributed to Larrat, B..

6 recordsLinked to original sources

bioRxiv2026

Cortical folding patterns are encoded in the geometry of the unfolded neocortex.

Cortical folding patterns are conserved across individuals of gyrencephalic species and are closely related to cytoarchitectural organisation, connectivity, and function. Early morphogen gradients have been proposed as the molecular source of positional information encoding these patterns - a gyral molecular protomap - but the contribution of neocortical geometry to this encoding has not been examined. Here we show that the geometry of the unfolded ferret brain guides the adult folding pattern before any folding has occurred. Using high-resolution MRI surface reconstructions from postnatal day (P) 0 to adults, we demonstrate that newborn neocortical curvature predicts mature curvature maps, sulcal-gyral fate, and fold orientation. Pre-folding curvature correlates with expression of key patterning genes, and a mediation analysis indicates that geometry at P0 is the principal predictor of sulcal-gyral fate at P6. Mechanical simulations show that regions of high curvature act as autonomous anchors that organise the folding pattern. These results suggest that neocortical geometry constitutes a form of positional information that complements molecular patterns in regulating cortical organisation, and that a complete account of cortical development requires the integration of geometric and mechanical processes alongside molecular signalling.

neuroscience↗

bioRxiv2025

Problem-solving without a cortex: inferior lobe drives goal-directed object manipulation in cichlid fish

Goal-directed object manipulation and problem-solving, which are necessary to evolve tool use behaviors, have long been linked to the expansion of the telencephalon in mammals and birds. Here, we show that goal-directed object manipulation in cichlid fish is driven by a non-telencephalic brain structure, the inferior lobe. Using manganese-enhanced MRI (MEMRI) on an ultra-high field 17.2 Tesla MRI system, we show that the inferior lobe is activated during a puzzle-box opening task. Furthermore, magnetic resonance (MR)-guided High Intensity Focused Ultrasound (HIFU) lesions profoundly impair fine motor coordination during this task without affecting general locomotion or motivation. These results reveal that cortex-like cognitive functions can arise from non-telencephalic brain structures in teleosts. With no homolog in tetrapods, the inferior lobe is a critical hub for flexible behavior in teleost fish. Our findings highlight the existence of alternative neural architectures for the emergence of complex cognition.

neuroscience↗

bioRxiv2025

Functional Brain Imaging and Targeted Lesion Studies Using Manganese-Enhanced MRI and Focused Ultrasound in Non-Conventional ModelSpecies

Linking behavior to its neuroanatomical basis in non-conventional model species remains a significant challenge due to the scarcity of imaging and molecular tools. Commonly used approaches such as electrophysiological recordings rely on precise stereotaxic atlases or species-specific antibodies, while optogenetics requires transgenic lines which are largely unavailable beyond classical model organisms (e.g., mice, rats, zebrafish). Moreover, surgical lesion studies, a staple for verifying brain structure and behavior relationships, are logistically complex in species lacking atlases or living in aquatic environments. Here, we present a protocol integrating Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) and MR-guided High-Intensity Focused Ultrasound (HIFU) to overcome these limitations, which we demonstrate in the convict cichlid (Amatitlania nigrofasciata), a teleost fish lacking conventional neuroscience tools. MEMRI enables non-invasive, sub-millimeter resolution mapping of brain activity during behavior, and HIFU facilitates precise, surgery-free lesioning of targeted regions, adaptable to species without stereotaxic atlases. This combined approach offers a versatile, broadly applicable framework for linking brain structure and behavior in non-model organisms, advancing evolutionary and comparative neuroscience.

neuroscience↗

bioRxiv2024

Repeated low-intensity focused ultrasound led to microglial profile changes at long term in TgF344-AD rats

Alzheimers disease (AD), the most common cause of dementia, represents one of the main clinical challenges of the century as the number of patients is predicted to triple by 2050. Despite the recent approval of three monoclonal antibodies targeting Amyloid {beta} (A{beta}) aggregates by the Food and Drug Administration (FDA), immunotherapies still face challenges due to the difficulty of antibodies crossing the blood-brain barrier (BBB). This necessitates administering large doses of drugs to achieve their therapeutic effects, which is associated with significant side effects. In this context, low-intensity focused ultrasound (LiFUS) appears as an innovative and non-invasive method which, in association with intravenous injection of microbubbles (MB), leads to a transient BBB opening. This innovative strategy has been extensively studied in different preclinical models and more recently in human clinical trials, particularly in the context of AD. LiFUS+MB increases the inflammatory response at short-term, but the time course of this response is not consistent between studies, certainly due to the discrepancy between LiFUS protocols used. Moreover, the impact at longer term is understudied and the mechanisms underlying this effect are still not well understood. In our study, we therefore used the TgF344-AD rat model of AD to investigate the effect of a single or multiple exposures to LiFUS+MB in a large volume of the brain on inflammatory response, tauopathy and amyloid load, at both early and advanced stages. The ultrasound attenuation through the skull was corrected to apply a peak negative acoustic pressure of 450 kPa in all treated animals. At an advanced disease stage, single LiFUS+MB exposure induces a slight astrocyte and microglial response 24 hours post-treatment whereas chronic LiFUS treatment is associated with a transient inflammatory response predominantly affecting microglial cells, which is no longer detectable 6 weeks post-treatment. At an early stage of pathology, LiFUS seems to induce microglial reprogramming, leading to the adaptation of gene expression related to key functions such as inflammatory response, mitochondrial and energetic metabolism. In our rat model and LiFUS+MB protocol conditions, a single LiFUS exposure reduced significantly highly aggregated A{beta}42 peptide concentration. Surprisingly, multiple exposures had this opposite effect at short-term but not at longer term.

neuroscience↗

bioRxiv2019

Comparison between diffusion MRI tractography and histological tract-tracing of cortico-cortical structural connectivity in the ferret brain

The anatomical wiring of the brain is a central focus in network neuroscience. Diffusion MRI tractography offers the unique opportunity to investigate the brain fiber architecture in vivo and non invasively. However, its reliability is still highly debated. Here, we explored the ability of diffusion MRI tractography to match invasive anatomical tract-tracing connectivity data of the ferret brain. We also investigated the influence of several state-of-the-art tractography algorithms on this match to ground truth connectivity data. Tract-tracing connectivity data were obtained from retrograde tracer injections into the occipital, parietal and temporal cortices of adult ferrets. We found that the relative densities of projections identified from the anatomical experiments were highly correlated with the estimates from all the studied diffusion tractography algorithms (Spearmans rho ranging from 0.67 to 0.91), while only small, non-significant variations appeared across the tractography algorithms. These results are comparable to findings reported in mouse and monkey, increasing the confidence in diffusion MRI tractography results. Moreover, our results provide insights into the variations of sensitivity and specificity of the tractography algorithms and hence, into the influence of choosing one algorithm over another.

neuroscience↗

bioRxiv2018

A computational approach for characterizing the structural basis of intrinsic coupling modes of the cerebral cortex

Intrinsic coupling modes (ICMs) provide a framework for describing the interactions of ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models as well as simple topological ingredients of SC were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are strongly related to SC, except when using ICM measures removing zero-lag synchronizations. Computational models are challenged to predict these ICM patterns consistently, and simple predictions from SC topological features can sometimes outperform them. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs bear a substantial relation to the underlying structural connectivity of the cerebral cortex.

neuroscience↗