scholarly journals Brain wiring and supragranular-enriched genes linked to protracted human frontal cortex development

2019 ◽  
Author(s):  
Jasmine P. Hendy ◽  
Emi Takahashi ◽  
Andre J. van der Kouwe ◽  
Christine J. Charvet
Keyword(s):  
White Matter ◽  
Frontal Cortex ◽  
Developmental Trajectories ◽  
Developmental Origins ◽  
Transcriptional Profiles ◽  
Voltage Gated ◽  
Cortical Projections ◽  
Human Frontal Cortex ◽  
Transcriptional Changes ◽  
Voltage Gated Channels

AbstractThe human frontal cortex is unusually large compared with many other species. The expansion of the human frontal cortex is accompanied by both connectivity and transcriptional changes. Yet, the developmental origins generating variation in frontal cortex circuitry across species remain unresolved. Nineteen genes, which encode filaments, synapse, and voltage-gated channels (e.g., NEFH, SYT2, VAMP1) are especially enriched in the supragranular layers of the cerebral cortex in humans relative to mice. The increased expression of these genes suggests enhanced cortico-cortical projections emerging from layer III in humans. We confirm that the expression of these supragranular-enriched genes is preferentially expressed in frontal cortex layer III in humans relative to mice. We demonstrate a concomitant expansion in cortico-cortical pathways projecting within the frontal cortex white matter in humans with diffusion MR tractography. To identify developmental sources of such variation, we compare frontal cortical white matter growth and developmental trajectories of transcriptional profiles of supragranular-enriched genes in humans and mice. We also use temporal changes in gene expression during postnatal development to control for variation in developmental schedules across species. The growth of the frontal cortex white matter and transcriptional profiles of supragranular genes are both protracted in humans relative to the timing of other transformations. These findings demonstrate that an expansion of projections emerging from the human frontal cortex is achieved by extending the duration of cortical circuitry development. Integrating RNA sequencing with neuroimaging level phenotypes is an effective strategy to assess deviations in developmental programs leading to variation in connections across species.

scholarly journals Brain Wiring and Supragranular-Enriched Genes Linked to Protracted Human Frontal Cortex Development

2020 ◽  
Vol 30 (11) ◽  
pp. 5654-5666 ◽  
Author(s):  
Jasmine P Hendy ◽  
Emi Takahashi ◽  
Andre J van der Kouwe ◽  
Christine J Charvet
Keyword(s):  
Gene Expression ◽  
Frontal Cortex ◽  
Species Differences ◽  
Developmental Origins ◽  
Human Cerebral Cortex ◽  
Cortical Circuitry ◽  
Human Frontal Cortex ◽  
Transcriptional Changes ◽  
Voltage Gated Channels ◽  
Corticocortical Projections

Abstract The human frontal cortex is unusually large compared with many other species. The expansion of the human frontal cortex is accompanied by both connectivity and transcriptional changes. Yet, the developmental origins generating variation in frontal cortex circuitry across species remain unresolved. Nineteen genes that encode filaments, synapse, and voltage-gated channels are especially enriched in the supragranular layers of the human cerebral cortex, which suggests enhanced corticocortical projections emerging from layer III. We identify species differences in connections with the use of diffusion MR tractography as well as gene expression in adulthood and in development to identify developmental mechanisms generating variation in frontal cortical circuitry. We demonstrate that increased expression of supragranular-enriched genes in frontal cortex layer III is concomitant with an expansion in corticocortical pathways projecting within the frontal cortex in humans relative to mice. We also demonstrate that the growth of the frontal cortex white matter and transcriptional profiles of supragranular-enriched genes are protracted in humans relative to mice. The expansion of projections emerging from the human frontal cortex arises by extending frontal cortical circuitry development. Integrating gene expression with neuroimaging level phenotypes is an effective strategy to assess deviations in developmental programs leading to species differences in connections.

Characterization of dopamine receptor of type 4 (D4) in human frontal cortex post-mortem

2001 ◽  
Vol 11 ◽  
pp. S282-S283
Author(s):  
D. Marazziti ◽  
I. Masala ◽  
G. Giannaccini ◽  
E. Di Nasso ◽  
L. Betti ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Dopamine Receptor ◽  
Post Mortem ◽  
Human Frontal Cortex

Postnatal ontogeny of GTP binding protein in the human frontal cortex

Life Sciences ◽  
1999 ◽  
Vol 65 (22) ◽  
pp. 2315-2323 ◽  
Author(s):  
Hiroki Ozawa ◽  
Wataru Ukai ◽  
Johannes Kornhuber ◽  
Takafumi Yamaguchi ◽  
Lutz Froelich ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Binding Protein ◽  
Postnatal Ontogeny ◽  
Gtp Binding Protein ◽  
Gtp Binding ◽  
Human Frontal Cortex

scholarly journals A cortical immune network map identifies distinct microglial transcriptional programs associated with β-amyloid and Tau pathologies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ellis Patrick ◽  
Marta Olah ◽  
Mariko Taga ◽  
Hans-Ulrich Klein ◽  
Jishu Xu ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Frontal Cortex ◽  
Brain Aging ◽  
Immune Network ◽  
Tau Pathology ◽  
Cellular Mechanisms ◽  
Activated Microglia ◽  
Human Frontal Cortex ◽  
Β Amyloid ◽  
The Many

AbstractMicroglial dysfunction has been proposed as one of the many cellular mechanisms that can contribute to the development of Alzheimer’s disease (AD). Here, using a transcriptional network map of the human frontal cortex, we identify five modules of co-expressed genes related to microglia and assess their role in the neuropathologic features of AD in 540 subjects from two cohort studies of brain aging. Two of these transcriptional programs—modules 113 and 114—relate to the accumulation of β-amyloid, while module 5 relates to tau pathology. We replicate these associations in brain epigenomic data and in two independent datasets. In terms of tau, we propose that module 5, a marker of activated microglia, may lead to tau accumulation and subsequent cognitive decline. We validate our model further by showing that three representative module 5 genes (ACADVL, TRABD, and VASP) encode proteins that are upregulated in activated microglia in AD.

Cd(2+)-induced injury in CNS white matter

1996 ◽  
Vol 76 (5) ◽  
pp. 3264-3273 ◽  
Author(s):  
R. Fern ◽  
J. A. Black ◽  
B. R. Ransom ◽  
S. G. Waxman
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Mitochondrial Respiration ◽  
Time Course ◽  
White Matter Injury ◽  
Neurological Injury ◽  
Antimycin A ◽  
Optic Nerves ◽  
Voltage Gated ◽  
Ca2 Channels

1. The affect of extracellular Cd2+ on CNS white matter was studied using an isolated rat optic nerve preparation. A 100-min exposure to 200 microM Cd2+ reduced the area of the compound action potential (CAP) recorded from the optic nerve to 32.6 +/- 3.8% (mean +/- SE) of the preexposure area, compared with a reduction to 74.9 +/- 2.9% after 100 min in control conditions (P > 0.001). This CAP reduction was not reversed after 120 min of reperfusion with Cd(2+)-free solution, or by perfusion with Cd2+ chelators. 2. Cd(2+)-induced CAP loss occurred in the absence of extracellular Ca2+. Increasing extracellular Ca2+ concentration to 16 mM, however, prevented Cd(2+)-induced CAP loss. Once evident, Cd(2+)-induced CAP reduction could not subsequently be reversed by addition of 16 mM Ca2+. 3. Low concentrations of Cd2+ (60 microM) did not significantly reduce CAP area. This concentration of Cd2+ combined with high extracellular K+ (30 mM) caused CAP loss that was blocked by 10 microM nifedipine, an antagonist of L-type voltage-gated Ca2+ channels. 4. Treatment with pharmacological inhibitors of membrane proteins known to be inhibited by Cd2+ did not affect the CAP. These included inhibitors of voltage-gated Ca2+ channels, Ca(2+)-activated K+ channels, Ca(2+)-ATPase and the Na+/Ca2+ exchanger. 5. Treatment with pharmacological agents that inhibit calmodulin or disrupt tubulin, two intracellular proteins affected by Cd2+, did not affect CAP area. 6. The effect of Cd2+ was not prevented by pretreatment with (+)-cyanidanol-3, an agent that prevents Cd(2+)-induced lipid peroxidation. 7. Treatment with antimycin A, a inhibitor of mitochondrial respiration, resulted in irreversible CAP reduction with a time course and extent similar to that produced by 200 microM Cd2+. Cd(2+)-induced CAP reduction was prevented by 1 mM cysteine, which prevents Cd(2+)-induced disruption of mitochondrial respiration. 8. The ultrastructure of optic nerves exposed to 200 microM Cd2+ for 100 min was characterized by swollen mitochondria with disrupted cristae and dissolution of microtubules, which were replaced by flocculent debris. Occasional regions of axonal swelling and empty spaces beneath the myelin also were found. Qualitatively similar changes in mitochondria and cytoskeletal elements were found in optic nerves exposed to antimycin A for 100 min. Astrocytes also displayed disrupted mitochondria and had an electron-lucent appearance under both conditions. 9. The neurological injury produced by exposure to Cd2+ is characterized by lesions of CNS white matter. Our results indicate that Cd(2+)-induced white matter injury in vitro results largely from disruption of mitochondrial respiration after Cd2+ influx through routes that include voltage-gated Ca2+ channels.

Voltage-Dependent Properties of Dendrites That Eliminate Location-Dependent Variability of Synaptic Input

1999 ◽  
Vol 81 (2) ◽  
pp. 535-543 ◽  
Author(s):  
Erik P. Cook ◽  
Daniel Johnston
Keyword(s):  
Synaptic Input ◽  
Outward Current ◽  
Compartment Model ◽  
Inward Current ◽  
Voltage Gated ◽  
Cable Properties ◽  
Dendritic Membrane ◽  
Voltage Dependent ◽  
Dendritic Location ◽  
Voltage Gated Channels

Voltage-dependent properties of dendrites that eliminate location-dependent variability of synaptic input. We examined the hypothesis that voltage-dependent properties of dendrites allow for the accurate transfer of synaptic information to the soma independent of synapse location. This hypothesis is motivated by experimental evidence that dendrites contain a complex array of voltage-gated channels. How these channels affect synaptic integration is unknown. One hypothesized role for dendritic voltage-gated channels is to counteract passive cable properties, rendering all synapses electrotonically equidistant from the soma. With dendrites modeled as passive cables, the effect a synapse exerts at the soma depends on dendritic location (referred to as location-dependent variability of the synaptic input). In this theoretical study we used a simplified three-compartment model of a neuron to determine the dendritic voltage-dependent properties required for accurate transfer of synaptic information to the soma independent of synapse location. A dendrite that eliminates location-dependent variability requires three components: 1) a steady-state, voltage-dependent inward current that together with the passive leak current provides a net outward current and a zero slope conductance at depolarized potentials, 2) a fast, transient, inward current that compensates for dendritic membrane capacitance, and 3) both αamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid– and N-methyl-d-aspartate–like synaptic conductances that together permit synapses to behave as ideal current sources. These components are consistent with the known properties of dendrites. In addition, these results indicate that a dendrite designed to eliminate location-dependent variability also actively back-propagates somatic action potentials.

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