Biology subjects

Lent, R.

Publications and source records attributed to Lent, R..

3 recordsLinked to original sources

bioRxiv2023

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations. Significance statementBrain connectivity is a central topic in neuroscience. Understanding how brain areas can communicate allows for the comprehension of brain structure and function. We have described in rodents a new commissure pathway that connects the cortex to the contralateral thalamus. Here, we investigate whether this pathway exists in non-human primates and humans. The presence of these commissures poses the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

neuroscience↗

bioRxiv2021

Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline. Summary StatementZika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

neuroscience↗

bioRxiv2019

The reliability of the isotropic fractionator method for counting total cells and neurons

BackgroundThe Isotropic Fractionator (IF) is a method used to determine the cellular composition of nervous tissue. It has been mostly applied to assess variation across species, where differences are expected to be large enough not to be masked by methodological error. However, understanding the sources of variation in the method is important if the goal is to detect smaller differences, for example, in same-species comparisons. Comparisons between different mice strains suggest that the IF is consistent enough to detected these differences. Nevertheless, the internal validity of the method has not yet been examined directly.\n\nMethodIn this study, we evaluate the reliability of the IF method for the determination of cellular and neuronal numbers. We performed repeated cell counts of the same material by different experimenters to quantify different sources of variation.\n\nResultsIn total cell counts, we observed that for the cerebral cortex most of the variance was at the counter level. For the cerebellum, most of the variance is attributed to the sample itself. As for neurons, random error along with the immunological staining correspond to most of the variation, both in the cerebral cortex and in the cerebellum. Test-retest reliability coefficients were relatively high, especially for cell counts.\n\nConclusionsAlthough biases between counters and random variation in staining could be problematic when aggregating data from different sources, we offer practical suggestions to improve the reliability of the method. While small, this study is a most needed step towards more precise measurement of the brains cellular composition.\n\nHighlightsO_LIMost variance in cell counts was between counters ({eta} = 0.58) for cerebral cortices.\nC_LIO_LIFor cerebella, most of the variance was attributed to the samples ({eta} = 0.49).\nC_LIO_LIVariance in immunocytochemical counts was mostly residual/random ({eta} > 0.8).\nC_LIO_LITest-retest reliability was high (same counter, same sample).\nC_LIO_LIPractical suggestions are offered to improve the reliability of the method.\nC_LI

neuroscience↗