Biology subjects

Meaney, M.

Publications and source records attributed to Meaney, M..

4 recordsLinked to original sources

bioRxiv2025

Perinatal environmental enrichment affects murine neonates' brain structure before their active engagement with environment

Early life experiences shape individuals. Environmental enrichment, an experimental paradigm used to study the effect of increased environmental complexity and novelty in animal models, has long been recognised for its broad effect on nervous system function and behaviour. In adult rodents, structural changes in the brain due to enriched environments are well documented, notably in the hippocampus. However, the effect of environmental enrichment on the developing brain during early life is not well understood. This study aims to investigate how environmental enrichment affects brain development during the critical perinatal period, and how such effects compare to those observed during adulthood. We use high-resolution MRI to measure the brain structure of mouse neonates at postnatal day 7, born either in an enriched or a standard environment. We show that rodents exhibit brain structure differences as early as postnatal day 7. However, the regional changes observed differ from those in adulthood: hippocampal changes are limited, but changes in the hindbrain, the dorsal striatum, and the medial habenula are strong. Given the lack of direct interaction between neonates and the environment at P7, we hypothesised that maternal care may mediate these effects. We show that maternal care differs between enriched and standard environments, that maternal care correlates with brain structure changes in the neonates, and that maternal care and enriched environment affect brain structure similarly. This suggests that early changes in brain structure due to environmental enrichment are at least partly mediated by maternal care. This study provides novel insight into the differential effect of enriched environment on early brain development in rodents.

neuroscience↗

bioRxiv2023

In-vivo whole-cortex estimation of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here we non-invasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically-plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the GABA-agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 years old) and Asian (7.2 to 7.9 years old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth. SignificanceHealthy brain function requires a delicate balance of neural excitation (E) and inhibition (I). In animals, this balance - the E/I ratio - is known to decrease with the maturation of inhibitory circuitry during healthy development. However, in humans, the normative development of cortex-wide E/I ratio remains unclear. Here, we use a biophysical model and non-invasive brain scans to estimate a marker of E/I ratio. Spatial changes in our E/I ratio marker are consistent with a drug that decreases E/I ratio. We also find that our cortex-wide E/I ratio marker decreases during development. Furthermore, North American and Asian children with lower E/I ratio, especially in higher-order cortex, have better cognitive performance. Overall, E/I ratio is a potential index of healthy neurocognitive development.

neuroscience↗

bioRxiv2022

Homotopic local-global parcellation of the human cerebral cortex from resting-state functional connectivity

Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations. However, the lack of homotopic correspondence between left and right Schaefer parcels has limited their use for brain lateralization studies. Here, we extend our previous model to derive homotopic areal-level parcellations. Using resting-fMRI and task-fMRI across diverse scanners, acquisition protocols, preprocessing and demographics, we show that the resulting homotopic parcellations are as homogeneous as the Schaefer parcellations, while being more homogeneous than five publicly available parcellations. Furthermore, weaker correlations between homotopic parcels are associated with greater lateralization in resting network organization, as well as lateralization in language and motor task activation. Finally, the homotopic parcellations agree with the boundaries of a number of cortical areas estimated from histology and visuotopic fMRI, while capturing sub-areal (e.g., somatotopic and visuotopic) features. Overall, these results suggest that the homotopic local- global parcellations represent neurobiologically meaningful subdivisions of the human cerebral cortex and will be a useful resource for future studies. Multi-resolution parcellations estimated from 1479 participants are publicly available (GITHUB_LINK).

neuroscience↗

bioRxiv2018

Genetic and behavioural requirements for structural brain plasticity

1Human MRI studies show that experience can lead to changes in the volume of task-specific brain regions; however, the behavioural and molecular processes driving these changes remain poorly understood. Here, we used in-vivo mouse MRI and RNA sequencing to investigate the neuroanatomical and transcriptional changes induced by environmental enrichment, exercise, and social interaction. Additionally, we asked whether the volume changes require CREB, a transcription factor critical for memory formation and neuronal plasticity. Enrichment rapidly increased cortical and hippocampal volume, and these effects were not attributable to exercise or social interaction. Instead, they likely arise from learning and sensorimotor experience. Nevertheless, the volume changes were not attenuated in mice with memory impairments caused by loss of CREB, indicating that these effects are driven by processes distinct from this canonical learning and memory pathway. Finally, within brain regions that underwent volume changes, enrichment increased the expression of genes associated with axonogenesis, dendritic spine development, synapse structural plasticity, and neurogenesis, suggesting these processes underlie the volume changes detected with MRI.

neuroscience↗