scholarly journals The natural axis of transmitter receptor distribution in the human cerebral cortex

2021 ◽  
Vol 118 (3) ◽  
pp. e2020574118
Author(s):  
Alexandros Goulas ◽  
Jean-Pierre Changeux ◽  
Konrad Wagstyl ◽  
Katrin Amunts ◽  
Nicola Palomero-Gallagher ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Receptor Density ◽  
Human Cerebral Cortex ◽  
Metabotropic Receptors ◽  
Cortical Organization ◽  
Multiple Dimensions ◽  
Molecular Machinery ◽  
Organizational Feature ◽  
Transmitter Receptors ◽  
Organizational Principles

Transmitter receptors constitute a key component of the molecular machinery for intercellular communication in the brain. Recent efforts have mapped the density of diverse transmitter receptors across the human cerebral cortex with an unprecedented level of detail. Here, we distill these observations into key organizational principles. We demonstrate that receptor densities form a natural axis in the human cerebral cortex, reflecting decreases in differentiation at the level of laminar organization and a sensory-to-association axis at the functional level. Along this natural axis, key organizational principles are discerned: progressive molecular diversity (increase of the diversity of receptor density); excitation/inhibition (increase of the ratio of excitatory-to-inhibitory receptor density); and mirrored, orderly changes of the density of ionotropic and metabotropic receptors. The uncovered natural axis formed by the distribution of receptors aligns with the axis that is formed by other dimensions of cortical organization, such as the myelo- and cytoarchitectonic levels. Therefore, the uncovered natural axis constitutes a unifying organizational feature linking multiple dimensions of the cerebral cortex, thus bringing order to the heterogeneity of cortical organization.

scholarly journals The natural axis of transmitter receptor distribution in the human cerebral cortex

2020 ◽  
Author(s):  
Alexandros Goulas ◽  
Jean-Pierre Changeux ◽  
Konrad Wagstyl ◽  
Katrin Amunts ◽  
Nicola Palomero-Gallagher ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Receptor Density ◽  
Human Cerebral Cortex ◽  
Metabotropic Receptors ◽  
Cortical Organization ◽  
Multiple Dimensions ◽  
Molecular Machinery ◽  
Organizational Feature ◽  
Transmitter Receptors ◽  
Organizational Principles

Transmitter receptors constitute a key component of the molecular machinery for inter-cellular communication in the brain. Recent efforts have mapped the density of diverse transmitter receptors across the human cerebral cortex with an unprecedented level of detail. Here, we distil these observations into key organizational principles. We demonstrate that receptor densities form a natural axis in the human cerebral cortex, reflecting decreases in differentiation at the level of laminar organization, and a sensory-to-association axis at the functional level. Along this natural axis, key organizational principles are discerned: progressive molecular diversity (increase of the diversity of receptor density), excitation/inhibition (increase of the ratio of excitatory-to-inhibitory receptor density) and mirrored, orderly changes of the density of ionotropic and metabotropic receptors. The uncovered natural axis formed by the distribution of receptors aligns with the axis that is formed by other dimensions of cortical organization, such as the myelo- and cytoarchitectonic levels. Therefore, the uncovered natural axis constitutes a unifying organizational feature linking multiple dimensions of the cerebral cortex, thus bringing order to the heterogeneity of cortical organization.

scholarly journals Correlation of receptor density and mRNA expression patterns in the human cerebral cortex

2021 ◽  
Author(s):  
Matej Murgaš ◽  
Paul Michenthaler ◽  
Murray Bruce Reed ◽  
Gregor Gryglewski ◽  
Rupert Lanzenberger
Keyword(s):  
Cerebral Cortex ◽  
Mrna Expression ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Molecular Targets ◽  
Brain Atlas ◽  
Receptor Density ◽  
Rna Seq ◽  
Human Cerebral Cortex ◽  
Proteomic Data

Changes in distribution of associated molecular targets have been reported across several neuropsychiatric disorders. However, the high-resolution topology of most proteins is unknown and simultaneous in vivo measurement in multi-receptor systems is complicated. To account for the missing proteomic information, mRNA transcripts are typically used as a surrogate. Nonetheless, post-transcriptional and post-translational processes might cause the discrepancy between the final distribution of proteins and gene expression patterns. Therefore, this study aims to investigate ex vivo links between mRNA expression and corresponding receptor density in the human cerebral cortex. To this end, autoradiography data on the density of 15 different receptors in 38 brain regions were correlated with the expression patterns of 50 associated genes derived from microarray data (mA), RNA sequencing data (RNA-Seq) provided by the Allen Human Brain Atlas and predicted mRNA expression patterns (pred-mRNA). Spearman's rank correlation was used to evaluate the possible links between proteomic data and mRNA expression patterns. Correlations between mRNA and protein density varied greatly between targets: Positive associations were found for e.g. the serotonin 1A (pred-mRNA: rs = 0.708; mA: rs = 0.601) or kainate receptor (pred-mRNA: rs = 0.655; mA: rs = 0.601; RNA-Seq: rs = 0.575), while most of the investigated target receptors showed low or negative correlations. The high variability in the correspondence of mRNA expression and receptor warrants caution when inferring the topology of molecular targets in the brain from transcriptome data. This highlights the longstanding value of molecular imaging data and the need for comprehensive proteomic data.

C-fos, ERK1/2, MAP2, NOTCH1 Proteins Expression Patterns in Human Cerebral Cortex Neurons after Ischemic Stroke

2020 ◽  
Vol 75 (3) ◽  
pp. 226-233
Author(s):  
Svetlana P. Sergeeva ◽  
Aleksey V. Lyundup ◽  
Valery V. Beregovykh ◽  
Petr F. Litvitskiy ◽  
Aleksey A. Savin ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Ischemic Stroke ◽  
Expression Patterns ◽  
Immunohistochemical Method ◽  
Left Middle Cerebral Artery ◽  
Contralateral Hemisphere ◽  
Human Cerebral Cortex ◽  
Fos Protein ◽  
Urgent Task ◽  
Indirect Immunoperoxidase

Background. The search for protein (these include c-fos, ERK1/2, MAP2, NOTCH1) expression that provide neuroplasticity mechanisms of the cerebral cortex after ischemic stroke (IS) patterns is an urgent task. Aims to reveal c-fos, ERK1/2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after IS. Materials and methods. We studied 9 left middle cerebral artery (LMCA) IS patients cerebral cortex samples from 3 zones: 1 the zone adjacent to the necrotic tissue focus; 2 zone remote from the previous one by 47 cm; 3 zone of the contralateral hemisphere, symmetric to the IS focus. Control samples were obtained from 3 accident died people. Identification of targeted proteins NSE, c-fos, ERK1/2, MAP2, NOTCH1 was performed by indirect immunoperoxidase immunohistochemical method. Results. Moving away from the ischemic focus, there is an increase in the density of neurons and a decrease in the damaged neurons proportion, the largest share of c-fos protein positive neurons in zone 2, NOTCH1 positive neurons in zone 1, smaller fractions of ERK1/2 and MAP2 positive neurons compared to the control only in samples of zone 1. Conclusions. With the IS development, the contralateral hemisphere is intact tissue increased activation zone, while the zones 1 and 2 have pathological activation signs. In zone 1 of the range, the adaptive response of the tissue decreases, and in zone 2 it expands. Therefore, a key target for therapeutic intervention is zone 2.

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