Increased Cortical Expression of Two Synaptogenic Thrombospondins in Human Brain Evolution

Cáceres, Mario; Suwyn, Carolyn; Maddox, Marcelia; Thomas, James W.; Preuss, Todd M.

doi:10.1093/cercor/bhl140

Cited by 86 publications

(74 citation statements)

References 46 publications

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“…S2C). Similarly, thrombospondin 4 (THBS4), previously shown to be associated with synaptic functions and synapse formation (Caceres et al 2003(Caceres et al , 2007, also shows significantly higher expression in the human PFC compared with PFCs of the other two species throughout adulthood. This implies that humans might sustain higher levels of synaptogenesis or synaptic activity throughout adult life.…”

Section: Discussionmentioning

confidence: 98%

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Liu¹,

Somel²,

Tang³

et al. 2012

Genome Res.

219

216

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Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human-specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functions and represents an extreme shift in the timing of synaptic development in the prefrontal cortex, but not the cerebellum. Consequently, peak expression of synaptic genes in the prefrontal cortex is shifted from <1 yr in chimpanzees and macaques to 5 yr in humans. This result was supported by protein expression profiles of synaptic density markers and by direct observation of synaptic density by electron microscopy. Mechanistically, the human-specific change in timing of synaptic development involves the MEF2A-mediated activity-dependent regulatory pathway. Evolutionarily, this change may have taken place after the split of the human and the Neanderthal lineages.

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Section: Discussionmentioning

confidence: 98%

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Liu¹,

Somel²,

Tang³

et al. 2012

Genome Res.

219

216

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“…However, the clear differences in behavioral and cognitive development between enculturated apes and humans point to particular neural specializations that make the human brain-but not the brain of great apes-extremely responsive to exogenous influences. In this light, several comparative studies have shown molecular and microstructural specializations in the human brain indicating an increased level of synaptic plasticity (21,22), which might be linked to increased learning abilities.…”

mentioning

confidence: 98%

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

Gómez‐Robles

Hopkins

Schapiro

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

164

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The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. brain evolution | plasticity | hominins | neocortex | altriciality C ompared with nonhuman primates, human brains are significantly enlarged, reorganized, and have a disproportionately expanded neocortex (1-3). The fossil evidence demonstrates that these changes occurred in the hominin lineage over the last ∼6-8 My (4-9) in parallel with modifications to neurodevelopmental rates (10-13). Although some of these changes have been linked to certain genetic variants in the human lineage [either shared with other late hominin species or exclusive to modern humans (14, 15)], exploring brain evolution in hominins is challenging because of the limitations of the endocranial fossil record (4, 5). Comparisons of chimpanzee and human brains therefore are essential to reveal the neural traits that differ between the two species, that underlie their behavioral specializations, and that must have evolved after they split from their last common ancestor.Human behavioral and cognitive development is highly dependent on cultural influences and social learning (16,17). Notably, modern human behavioral adaptations for living in diverse habitats depend on skills and information learned from others (18). Similarly, it has been demonstrated that enculturated great apes perform better in different tasks related to physical and, especially, social cognition (19), underscoring the importance of environmental influences in shaping behavior. These observations are congruent with experimental studies in mouse models showing that variation in sensory experience early in postnatal life causes reorganization of neural circuits that underlie...

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“…This interpretation is supported by evidence that the cortical regions that develop later in human ontogeny also underwent the greatest expansion during human brain evolution (18,19), suggesting that evolutionary selection to enlarge these regions was accompanied by a prolongation of their development. Among these regions, the prefrontal cortex, which shows particularly extended maturation in humans relative to macaques, has also been reported to exhibit uniquely human neuroanatomical and molecular specializations (20)(21)(22)(23)(24)(25). However, because macaques and humans shared a last common ancestor ∼25 million y ago, it is currently unclear whether features that distinguish human cortical development (i.e., extended period of synaptogenesis and maturational delay of prefrontal pyramidal neurons) are unique to our lineage, or if they evolved before the divergence of modern humans and more closely related great ape species, such as chimpanzees.…”

mentioning

confidence: 99%

Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans

Bianchi

Stimpson

Duka

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

114

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Neocortical development in humans is characterized by an extended period of synaptic proliferation that peaks in mid-childhood, with subsequent pruning through early adulthood, as well as relatively delayed maturation of neuronal arborization in the prefrontal cortex compared with sensorimotor areas. In macaque monkeys, cortical synaptogenesis peaks during early infancy and developmental changes in synapse density and dendritic spines occur synchronously across cortical regions. Thus, relatively prolonged synapse and neuronal maturation in humans might contribute to enhancement of social learning during development and transmission of cultural practices, including language. However, because macaques, which share a last common ancestor with humans ∼25 million years ago, have served as the predominant comparative primate model in neurodevelopmental research, the paucity of data from more closely related great apes leaves unresolved when these evolutionary changes in the timing of cortical development became established in the human lineage. To address this question, we used immunohistochemistry, electron microscopy, and Golgi staining to characterize synaptic density and dendritic morphology of pyramidal neurons in primary somatosensory (area 3b), primary motor (area 4), prestriate visual (area 18), and prefrontal (area 10) cortices of developing chimpanzees (Pan troglodytes). We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3-5 y). Moreover, similar to findings in humans, dendrites of prefrontal pyramidal neurons developed later than sensorimotor areas. These results suggest that evolutionary changes to neocortical development promoting greater neuronal plasticity early in postnatal life preceded the divergence of the human and chimpanzee lineages.evolution | Golgi stain | brain | ontogeny

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Increased Cortical Expression of Two Synaptogenic Thrombospondins in Human Brain Evolution

Cited by 86 publications

References 46 publications

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans

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