Genetic Regulation of Prefrontal Cortex Development and Function

Author(s):  
Jeremy A. Cholfin ◽  
John L. R. Rubenstein
2016 ◽  
Vol 36 (1) ◽  
pp. 1-8
Author(s):  
Masataka Watanabe

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander GJ Skorput ◽  
Stephanie M Lee ◽  
Pamela WL Yeh ◽  
Hermes H Yeh

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.


2021 ◽  
pp. 1-18
Author(s):  
Jacob A. Miller ◽  
Mark D'Esposito ◽  
Kevin S. Weiner

Stuss considered the human prefrontal cortex (pFC) as a “cognitive globe” [Stuss, D. T., & Benson, D. F. Neuropsychological studies of the frontal lobes. Psychological Bulletin, 95, 3–28, 1984] on which functions of the frontal lobe could be mapped. Here, we discuss classic and recent findings regarding the evolution, development, function, and cognitive role of shallow indentations or tertiary sulci in pFC, with the goal of using tertiary sulci to map the “cognitive globe” of pFC. First, we discuss lateral pFC (LPFC) tertiary sulci in classical anatomy and modern neuroimaging, as well as their development, with a focus on those within the middle frontal gyrus. Second, we discuss tertiary sulci in comparative neuroanatomy, focusing on primates. Third, we summarize recent findings showing the utility of tertiary sulci for understanding structural–functional relationships with functional network insights in ventromedial pFC and LPFC. Fourth, we revisit and update unresolved theoretical perspectives considered by C. Vogt and O. Vogt (Allgemeinere ergebnisse unserer hirnforschung. Journal für Psychologie und Neurologie, 25, 279–462, 1919) and F. Sanides (Structure and function of the human frontal lobe. Neuropsychologia, 2, 209–219, 1964) that tertiary sulci serve as landmarks for cortical gradients. Together, the consideration of these classic and recent findings indicate that tertiary sulci are situated in a unique position within the complexity of the “cognitive globe” of pFC: They are the smallest and shallowest of sulci in pFC, yet can offer insights that bridge spatial scales (microns to networks), modalities (functional connectivity to behavior), and species. As such, the map of tertiary sulci within each individual participant serves as a coordinate system specific to that individual on which functions may be further mapped. We conclude with new theoretical and methodological questions that, if answered in future research, will likely lead to mechanistic insight regarding the structure and function of human LPFC.


2020 ◽  
Author(s):  
Tao Zhong ◽  
Cheng Wang ◽  
Jiangtao Hu ◽  
Xiaoyong Chen ◽  
Lili Niu ◽  
...  

Abstract Background: Rumen is an important digestive organ of ruminant. From fetal to adult stage, the morphology, structure and function of rumen have changed significantly. But the intrinsic genetic regulation is still limited. We previously reported a genome-wide expression profile of miRNAs in prenatal goat rumens. In the present study, we rejoined analyzed the transcriptomes of rumen miRNAs during prenatal (E60 and E135) and postnatal (D30 and D150) stages.Results: A total of 66 differentially expressed miRNAs (DEMs) were identified in the rumen tissues from D30 and D150 goats. Of these, 17 DEMs were consistently highly expressed in the rumens at the preweaning stages (E60, E135 and D30), while down-regulated at D150. Noteworthy, annotation analysis revealed that the target genes regulated by the DEMs were mainly enriched in MAPK signaling pathway, Jak-STAT signaling pathway and Ras signaling pathway. Interestingly, the expression of miR-148a-3p was significantly high in the embryonic stage and down-regulated at D150. The potential binding sites between miR-148a-3p and QKI were predicted by the TargetScan and verified by the dual luciferase report assay. The co-localization of miR-148a-3p and QKI was observed not in intestinal tracts but in rumen tissues by in situ hybridization. Moreover, the expression of miR-148a-3p in the epithelium was significantly higher than that in the other layers, suggesting that miR-148a-3p involve in the development of rumen epithelial cells by targeting QKI. Subsequently, miR-148a-3p inhibitor was found to induce the proliferation of GES-1 cells.Conclusions: Taken together, these results identified the DEMs involved in the development of rumen and provided an insight into the regulation mechanism of goat rumens during development.


2006 ◽  
Vol 29 (1) ◽  
pp. 22-22
Author(s):  
Antonino Raffone ◽  
Gary L. Brase

The tension between focusing on species similarities versus species differences (phylogenetic versus adaptationist approaches) recurs in discussions about the nature of neural connectivity and organization following brain expansion. Whereas Striedter suggests a primary role for response inhibition, other possibilities include dense recurrent connectivity loops. Computer simulations and brain imaging technologies are crucial in better understanding actual neuronal connectivity patterns.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Regina C. Lapate ◽  
Jason Samaha ◽  
Bas Rokers ◽  
Bradley R. Postle ◽  
Richard J. Davidson

AbstractMetacognitive awareness—the ability to know that one is having a particular experience—is thought to guide optimal behavior, but its neural bases continue to be the subject of vigorous debate. Prior work has identified correlations between perceptual metacognitive ability and the structure and function of lateral prefrontal cortex (LPFC); however, evidence for a causal role of this region in promoting metacognition is controversial. Moreover, whether LPFC function promotes metacognitive awareness of perceptual and emotional features of complex, yet ubiquitous face stimuli is unknown. Here, using model-based analyses following a causal intervention to LPFC in humans, we demonstrate that LPFC function promotes metacognitive awareness of the orientation of faces—although not of their emotional expressions. Collectively, these data support the causal involvement of the prefrontal cortex in metacognitive awareness, and indicate that the role of LPFC in metacognition encompasses perceptual experiences of naturalistic social stimuli.


2021 ◽  
Vol 46 (4) ◽  
pp. E441-E450
Author(s):  
Christoph Abé ◽  
Predrag Petrovic ◽  
William Ossler ◽  
William H. Thompson ◽  
Benny Liberg ◽  
...  

Background: Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders. Methods: We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics. Results: Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. Limitations: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined. Conclusion: Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging–genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.


2020 ◽  
Author(s):  
Jacob Miller ◽  
Mark D'Esposito ◽  
kevin weiner

Stuss (1984) considered the human prefrontal cortex (PFC) as a “cognitive globe” on which functions of the frontal lobe could be mapped. Here, we discuss classic and recent findings regarding the evolution, development, function, and cognitive role of shallow indentations, or tertiary sulci, in PFC with the goal of using tertiary sulci to map the “cognitive globe” of PFC. First, we discuss lateral PFC (LPFC) tertiary sulci in classical anatomy and modern neuroimaging, as well as their development, with a focus on those within the middle frontal gyrus (MFG). Second, we discuss tertiary sulci in comparative neuroanatomy, focusing on primates. Third, we summarize recent findings showing the utility of tertiary sulci for understanding structural-functional relationships with functional network insights in ventromedial and LPFC. Fourth, we revisit and update unresolved theoretical perspectives considered by Vogt and Vogt (1919) and Sanides (1964) that tertiary sulci serve as landmarks for cortical gradients. Together, the consideration of these classic and recent findings indicate that tertiary sulci are situated in a unique position within the complexity of the “cognitive globe” of PFC: they are the smallest and shallowest of sulci in PFC, yet can offer insights that bridge spatial scales (microns to networks), modalities (functional connectivity to behavior), and species. As such, the map of tertiary sulci within each individual participant serves as a coordinate system specific to that individual on which functions may be further mapped. We conclude with new theoretical and methodological questions that if answered in future research, will likely lead to mechanistic insight regarding the structure and function of human LPFC.


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