Biology subjects

Zilles, K.

Publications and source records attributed to Zilles, K..

5 recordsLinked to original sources

bioRxiv2021

Gradients of receptor expression in the macaque cortex

Dynamics and functions of neural circuits depend on synaptic interactions mediated by receptors. Therefore, a comprehensive map of receptor organization is needed to understand how different functions may emerge across distinct cortical regions. Here we use in-vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrate the receptor data with other anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of increasing receptor expression per neuron aligned with cortical hierarchy from early sensory cortex to higher cognitive areas. A second gradient, primarily driven by 5-HT1A receptors, peaks in the anterior and subcallosal cingulate, suggesting that the macaque may be a promising animal model for major depressive disorder. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration of information in higher cognitive areas.

neuroscience↗

bioRxiv2020

Multimodal 3D atlas of the macaque monkey motor and premotor cortex

In the present study we reevaluated the parcellation scheme of the macaque frontal agranular cortex by implementing quantitative cytoarchitectonic and multireceptor analyses, with the purpose to integrate and reconcile the discrepancies between previously published maps of this region. We applied an observer-independent and statistically testable approach to determine the position of cytoarchitectonic borders. Analysis of the regional and laminar distribution patterns of 13 different transmitter receptors confirmed the position of cytoarchitectonically identified borders. Receptor densities were extracted from each area and visualized as its "receptor fingerprint". Hierarchical and principal components analyses were conducted to detect clusters of areas according to the degree of (dis)similarity of their fingerprints. Finally, functional connectivity pattern of each identified area was analyzed with areas of prefrontal, cingulate, somatosensory and lateral parietal cortex and the results were depicted as "connectivity fingerprints" and seed-to-vertex connectivity maps. We identified 16 cyto- and receptor architectonically distinct areas, including novel subdivisions of the primary motor area 4 (i.e. 4a, 4p, 4m) and of premotor areas F4 (i.e. F4s, F4d, F4v), F5 (i.e. F5s, F5d, F5v) and F7 (i.e. F7d, F7i, F7s). Multivariate analyses of receptor fingerprints revealed three clusters, which first segregated the subdivisions of area 4 with F4d and F4s from the remaining premotor areas, then separated ventrolateral from dorsolateral and medial premotor areas. The functional connectivity analysis revealed that medial and dorsolateral premotor and motor areas show stronger functional connectivity with areas involved in visual processing, whereas 4p and ventrolateral premotor areas presented a stronger functional connectivity with areas involved in somatomotor responses. For the first time, we provide a 3D atlas integrating cyto- and multi-receptor architectonic features of the macaque motor and premotor cortex. This atlas constitutes a valuable resource for the analysis of functional experiments carried out with non-human primates, for modeling approaches with realistic synaptic dynamics, as well as to provide insights into how brain functions have developed by changes in the underlying microstructure and encoding strategies during evolution. HighlightsO_LIMultimodal analysis of macaque motor and premotor cortex reveals novel parcellation C_LIO_LI3D atlas with cyto- and multireceptor architectonic features of 16 (pre)motor areas C_LIO_LIPrimary motor area 4 is cyto- and receptor architectonically heterogeneous C_LIO_LI(Pre)motor areas differ in their functional connectivity fingerprints C_LI

neuroscience↗

bioRxiv2020

A dopamine gradient controls access to distributed working memory in monkey cortex

Dopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and biophysically-based model for distributed working memory that incorporates multiple neuron types and a dopamine gradient. The model captures an inverted U-shaped dependence of working memory on dopamine. The spatial distribution of mnemonic persistent activity matches that observed in over 90 experimental studies. We show that dopamine filters out irrelevant stimuli by enhancing inhibition of pyramidal cell dendrites. The level of cortical dopamine can also determine whether memory encoding is through persistent activity or an internal synaptic state. Taken together, our work represents a cross-level understanding that links molecules, cell types, recurrent circuit dynamics and a core cognitive function distributed across the cortex.

neuroscience↗

bioRxiv2019

Primate hippocampus size and organisation are predicted by sociality but not diet

The hippocampus is well known for its roles in spatial navigation and memory, but it is organized into regions that have different connections and functional specializations. Notably, the region CA2 has a role in social and not spatial cognition, as is the case for the regions CA1 and CA3 that surround it. Here we investigated the evolution of the hippocampus in terms of its size and organization in relation to the evolution of social and ecological variables in primates, namely home range, diet and different measures of group size. We found that the volumes within the whole cornu ammonis coevolve with group size, while only the volume of CA1 and subiculum can also be predicted by home range. On the other hand, diet, expressed as a shift from folivory toward frugivory, was shown to not be related to hippocampal volume. Interestingly, CA2 was shown to exhibit phylogenetic signal only against certain measures of group size but not with ecological factors. We also found that sex differences in the hippocampus are related to body size sex dimorphism. This is in line with reports of sex differences in hippocampal volume in non-primates that are related to social structure and sex differences in behaviour. Our findings support the notion that in primates, the hippocampus is a mosaic structure evolving in line with social pressures, where certain subsections evolve in line with spatial ability too.

evolutionary biology↗

bioRxiv2019

Automated segmentation of cortical layers in BigBrain reveals divergent cortical and laminar thickness gradients in sensory and motor cortices.

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. This atlas was derived from a 3D histological model of the human brain at 20 micron isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness, and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V and VI. In contrast, fronto-motor cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness and, ultimately, functional neuroanatomy.

neuroscience↗