scholarly journals A human-specific modifier of cortical circuit connectivity and function improves behavioral performance

2019 ◽  
Author(s):  
Ewoud R.E. Schmidt ◽  
Hanzhi T. Zhao ◽  
Jung M. Park ◽  
Jacob B. Dahan ◽  
Chris C. Rodgers ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Brain Evolution ◽  
Specific Gene ◽  
Behavioral Performance ◽  
Cortical Connectivity ◽  
Cortical Circuit ◽  
And Function ◽  
Circuit Function ◽  
And Behavior ◽  
Human Specific

SUMMARYThe remarkable cognitive abilities characterizing humans are thought to emerge from our unique features of cortical circuit architecture, including increased feedforward and feedback connectivity. However, our understanding of the evolutionary origin and nature of these changes in circuit connectivity, and how they impact cortical circuit function and behavior is currently lacking. Here, we demonstrate that expression of the human-specific gene duplication SRGAP2C leads to a specific increase in feedforward and feedback cortico-cortical connectivity. Moreover, humanized SRGAP2C mice display improved cortical sensory coding, and an enhanced ability to learn a cortex-dependent sensory discrimination task. Our results identify a novel substrate for human brain evolution whereby the emergence of SRGAP2C led to increased feedforward and feedback cortico-cortical connectivity, improved cortical sensory processing and enhanced behavioral performance.

A human-specific modifier of cortical connectivity and circuit function

Nature ◽  
2021 ◽  
Author(s):  
Ewoud R. E. Schmidt ◽  
Hanzhi T. Zhao ◽  
Jung M. Park ◽  
Mario Dipoppa ◽  
Mauro M. Monsalve-Mercado ◽  
...  
Keyword(s):  
Cortical Connectivity ◽  
Circuit Function ◽  
Human Specific

scholarly journals IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer s disease mouse model

2021 ◽  
Author(s):  
Niklas Lonnemann ◽  
Shirin Hosseini ◽  
Melanie Ohm ◽  
Karsten Hiller ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cognitive Abilities ◽  
Long Term Potentiation ◽  
Spine Density ◽  
Chronic Neuroinflammation ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Anti Inflammatory ◽  
And Function ◽  
And Behavior

The anti-inflammatory cytokine interleukin-37 (IL-37) is a member of the IL-1 family but not expressed in mice. We used a human IL 37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Those studies demonstrate an immune-modulatory role of IL-37 which can be characterized as an important suppressor of innate immunity. We investigated the functions of IL-37 in the CNS and explored the effects of IL-37 on neuronal architecture and function, microglia phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. Reduced spine density, activated microglia phenotype and impaired long-term potentiation (LTP) were observed in wild-type mice after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimer's disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent the loss of cognitive abilities in a mouse model of AD.

scholarly journals Author Correction: A human-specific modifier of cortical connectivity and circuit function

Nature ◽  
2022 ◽  
Author(s):  
Ewoud R. E. Schmidt ◽  
Hanzhi T. Zhao ◽  
Jung M. Park ◽  
Mario Dipoppa ◽  
Mauro M. Monsalve-Mercado ◽  
...  
Keyword(s):  
Cortical Connectivity ◽  
Circuit Function ◽  
Human Specific

scholarly journals Retrotransposons as Drivers of Mammalian Brain Evolution

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 376
Author(s):  
Roberto Ferrari ◽  
Nicole Grandi ◽  
Enzo Tramontano ◽  
Giorgio Dieci
Keyword(s):  
Cognitive Abilities ◽  
Large Scale ◽  
Transcriptional Control ◽  
Large Body ◽  
Three Dimensional ◽  
Brain Evolution ◽  
Cell Types ◽  
Brain Morphology ◽  
Mammalian Brain ◽  
And Function

Retrotransposons, a large and diverse class of transposable elements that are still active in humans, represent a remarkable force of genomic innovation underlying mammalian evolution. Among the features distinguishing mammals from all other vertebrates, the presence of a neocortex with a peculiar neuronal organization, composition and connectivity is perhaps the one that, by affecting the cognitive abilities of mammals, contributed mostly to their evolutionary success. Among mammals, hominids and especially humans display an extraordinarily expanded cortical volume, an enrichment of the repertoire of neural cell types and more elaborate patterns of neuronal connectivity. Retrotransposon-derived sequences have recently been implicated in multiple layers of gene regulation in the brain, from transcriptional and post-transcriptional control to both local and large-scale three-dimensional chromatin organization. Accordingly, an increasing variety of neurodevelopmental and neurodegenerative conditions are being recognized to be associated with retrotransposon dysregulation. We review here a large body of recent studies lending support to the idea that retrotransposon-dependent evolutionary novelties were crucial for the emergence of mammalian, primate and human peculiarities of brain morphology and function.

scholarly journals Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood

2020 ◽  
Author(s):  
William E. Medendorp ◽  
Akash Pal ◽  
Madison Waddell ◽  
Andreas Björefeldt ◽  
Christopher I. Moore ◽  
...  
Keyword(s):  
Experimental Approach ◽  
Pyramidal Neurons ◽  
Autism Spectrum ◽  
Inhibitory Neurons ◽  
Neocortical Neurons ◽  
And Function ◽  
Circuit Function ◽  
And Behavior ◽  
The Impact

SummaryIn leading models of Autism Spectrum Disorder, and in human data, the efficacy of outgoing cortical connectivity transitions from overly exuberant to languid from early development to adulthood. This transition begs the question of whether the early enhancement in excitation might be a common driver, across etiologies, of these symptoms. We directly tested this concept by chemogenetically driving neuronal activity in neocortical neurons during postnatal days 4-14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons, impaired recruitment of inhibitory neurons and reduced cortico-striatal communication. These results directly support the prediction that changed firing in developing circuits irreversibly alters adult circuit function that leads to maladaptive changes in behaviors. This experimental approach offers a valuable platform to study the impact of disruption of developmental neural activity on the formation and function of adult neural circuits and behavior.

scholarly journals Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

2018 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R. Long ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Progenitor Cell ◽  
Radial Glia ◽  
Specific Gene ◽  
Cell Type ◽  
Embryonic Mouse ◽  
Neuron Density ◽  
Developing Neocortex ◽  
Radial Dimension ◽  
Human Specific

AbstractThe evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. As a consequence, the postnatal ferret neocortex exhibits an increased neuron density in the upper cortical layers and expands in the radial dimension. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in developing ferret neocortex.

scholarly journals Human-specific ARHGAP11B is necessary and sufficient for human-type basal progenitor levels in primate brain organoids

2020 ◽  
Author(s):  
Jan Fischer ◽  
Jula Peters ◽  
Takashi Namba ◽  
Wieland B. Huttner ◽  
Michael Heide
Keyword(s):  
Genetic Manipulation ◽  
Primate Evolution ◽  
Specific Gene ◽  
Major Contributor ◽  
Human Neocortex ◽  
Primate Brain ◽  
Basal Progenitor ◽  
And Function ◽  
Necessary And Sufficient ◽  
Human Specific

AbstractBased on studies in various animal models, including developing ferret neocortex (Kalebic et al., 2018), the human-specific gene ARHGAP11B has been implicated in human neocortex expansion. However, the extent of its contribution to this expansion during primate evolution is unknown. Here we addressed this issue by genetic manipulation of ARHGAP11B levels and function in chimpanzee and human cerebral organoids. Interference with ARHGAP11B’s function in human cerebral organoids caused a massive decrease, down to a chimpanzee level, in the proliferation and abundance of basal progenitors, the progenitors thought to have a key role in neocortex expansion. Conversely, ARHGAP11B expression in chimpanzee cerebral organoids resulted in a doubling of cycling basal progenitors. Taken together, our findings demonstrate that ARHGAP11B is necessary and sufficient to maintain the elevated basal progenitor levels that characterize the fetal human neocortex, suggesting that this human-specific gene was a major contributor to neocortex expansion during human evolution.

scholarly journals Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R Long ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Progenitor Cell ◽  
Radial Glia ◽  
Specific Gene ◽  
Cell Type ◽  
Cortical Layers ◽  
Embryonic Mouse ◽  
Neuron Density ◽  
Developing Neocortex ◽  
Human Specific

The evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. Consequently, the postnatal ferret neocortex exhibits increased neuron density in the upper cortical layers and expands in both the radial and tangential dimensions. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in the developing ferret neocortex.

scholarly journals Human-Specific Genes, Cortical Progenitor Cells, and Microcephaly

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1209
Author(s):  
Michael Heide ◽  
Wieland B. Huttner
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Abilities ◽  
Functional Role ◽  
Brain Size ◽  
Cortical Development ◽  
Specific Gene ◽  
The Past ◽  
The Brain ◽  
Cortical Progenitor ◽  
Human Specific

Over the past few years, human-specific genes have received increasing attention as potential major contributors responsible for the 3-fold difference in brain size between human and chimpanzee. Accordingly, mutations affecting these genes may lead to a reduction in human brain size and therefore, may cause or contribute to microcephaly. In this review, we will concentrate, within the brain, on the cerebral cortex, the seat of our higher cognitive abilities, and focus on the human-specific gene ARHGAP11B and on the gene family comprising the three human-specific genes NOTCH2NLA, -B, and -C. These genes are thought to have significantly contributed to the expansion of the cerebral cortex during human evolution. We will summarize the evolution of these genes, as well as their expression and functional role during human cortical development, and discuss their potential relevance for microcephaly. Furthermore, we will give an overview of other human-specific genes that are expressed during fetal human cortical development. We will discuss the potential involvement of these genes in microcephaly and how these genes could be studied functionally to identify a possible role in microcephaly.

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