Unique development of the brain

• The development of the human neocortex


  • Strikingly plastic
  • Almost constant "work in progress"
• Whatever distinguishes humans from other primates must reside in the unique features of human development, especially in the development of the brain
• Phenomena that distinguish the development of the human brain from that of other species, including primates


  • Retention of the fetal neuronal growth rate after birth
  • Migration of cells from the proencephalon to the diencephalon
  • Activity of transcription
  • Specific form of the FOXP2 gene
  • Continuation of brain maturation into adulthood

  
• Retention of fetal neural growth rate in humans


  • Humans have rapid brain growth for about 2 years after birth
  • During early postnatal development we add approximately 250,0000 neurons/minute

  
• The human brain/body ratio is much greater than that of apes

  
• At birth the ratio of brain weight to body weight is similar for great apes and humans

  
• By adulthood the ratio for humans is 3.5 times that of apes

  
• Post Natal Brain Development

  • 30,000 synapse/second/sq cm of cortex are formed during the first few years of human life
  • This increase in neuron numbers may generate new modules that can acquire new functions, store new memories for use in thinking and forecasting, and enable learning by interconnecting among themselves and with prenatally generated neurons
  • It is in this early postnatal stage that intervention can raise IQ
  • This stage also sees much of the maturation of the neural circuitry as determined by axon diameter and myelination

  
• Migration of cells into the dorsal thalmus


  • Most neurons remain within the region of the brain in which they are formed
  • However in the human brain (and not the brains of mice or monkeys) certain neurons from the telencephon migrate into the diencephalon
  • Here they enter the thalmus, an area involved in memory and problem solving
  • The thalmus has grown especially large in humans

  
• The neurons from the telencephalon appear to contribute to those thalamic regions that distribute information to the cerebral cortex of the frontal lobes
• The developing human thalmus chemotactically attracts the telencephalon neurons, but this chemotaxis is not seen in mice
• The growth of the thalamus as a "relay station" that coordinates cortical functions may be one of the features distinguishing human brains from those of our animal cousins
• Transcriptional Activity


  • The proteins of the human and chimp brain are within experimental limits, identical
  • Nearly 99% of human and chimpanzee genomes are identical and it has been suggested that the difference between the species might reside in the amount of proteins made from their genes
  • Microarrays have provided evidence supporting this. Human brains produced over 5x more mRNA than chimp brains, while a comparison of genes expressed in their liver and blood showed a high similarity between human and chimp
  • This finding cannot rule out the presence of human specific brain messages but it does provide evidence that quantitative changes in gene expression may underlie some of our abilities

  
• The FOXP2 gene and speech and language


  • Spoken language is a uniquely human trait
  • Language entails the finescale control of the larynx and mouth
  • Individuals who are heterozygous for mutations at the FOXP2 locus have severe problems with language articulation and with forming sentences
  • Human FOXP2 has accumulated two amino acid changing mutations since our divergence from the common ancestor of human and chimp
  • These differences are significant, since human and chimpanzee forms of the Foxp2 protein differentially regulate more than 100 genes
  • In the mouse, the Foxp2 gene is expressed in the developing brain, but its major site of expression is the lung
  • In humans, FOXP2 is predominantly expressed in those brain regions that coordinate speech; these sites are abnormal in patients with FOXP2 deficiency
  • In the cortical regions regulating language and speech, the human-specific FoxP2 appears to promote the expression of specific transcripts during brain development
  • Although it is not certain that FOXP2 is the most critical gene for human language acquisition, it seems to be very important for allowing the orofacial movements and grammar characteristic of human speech
• Teenage brains


  • Until recently it was thought that after the initial growth of neurons during fetal development and early childhood, there were no more periods of rapid neural proliferation
  • However, MRI studies have shown that the brain keeps developing until around puberty, and not all areas of the brain mature simultaneously
  • Moreover, soon after puberty neuronal growth ceases and pruning occurs. This time of pruning correlates with the time when language acquisition becomes difficult. There is also a wave of myelin production at this time
  • Myelination is critical for the proper functioning of the neural areas and the greatest difference between brains in early puberty and those in early adulthood involve the frontal cortex
• Cerebral cortex


  • Is the outer layered structure of neural tissue
  • Massive expansion of the cortical surface and elaboration of its connections in humans originates from developmental events
  • Understanding the genetic regulation of cell number, neuronal migration to proper layers and ultimately their differentiation into specific phenotypes, is critical
  • Human cerebral cortex has expanded significantly relative to other hominids including introduction of new regions (frontal and temporal lobes)
  • Basic principles of brain development in all mammals conserved but modifications of developmental events during evolution produce quantitative and qualitative changes

  
• Cortical Expansion


  • Expansion of the cortex occurs primarily in surface area rather than in thickness
  • Neocortex comprises up to 80% of the brain mass
  • We have also known for a long time that the neocortex is subdivided into distinct cytoarchitectonic areas with neurons organized in horizontal layers (or laminae), and vertical (radial) columns or modules, which have increased in number, size, and complexity during cortical evolution

  
• ARHGAP11B


  • ARHGAP11B is a human-specific gene that amplifies basal progenitors, controls neural progenitor proliferation, and contributes to neocortex folding
  • It is capable of causing neocortex folding in mice
  • This likely reflects a role for ARHGAP11B in development and evolutionary expansion of the human neocortex
  • Changes in ARHGAP11B are one of several key genetic factors of recent brain evolution and difference of modern humans to (other) apes and Neanderthals
  • A 2016 study suggests, one mutation, a "single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex"