brain evolution and development

see also:

• the brain
• cerebrospinal fluid (CSF)
• consciousness

• in humans, the brain is the most expensive organ in the body requiring 20% of our energy, 75% of the human brain is neocortex
• complex reasoning arises from a combination of:
  • a fixed set of computational building blocks (memories, processes, representations, learning mechanisms), and,
  • knowledge through learned experiences

• all biologic cells have the ability to be electrically charged due to the differential of ion concentrations inside the cell compared with outside
  • some cells can propagate action potentials along their membranes:
    • some plant cells
    • muscle cells
    • neurons - the action potentials then release neurotransmitters at synaptic endings
• plants
  • plants do not have pain sensors, neural networks, or brains akin to animals, however:
    • plants have genes that are similar to those that specify components of animal nervous systems including glutamate receptors, and neurotransmitter pathway activators, such as as G-box proteins, and a family of “14-3-3” proteins, which act to bind various signaling proteins, and 30-40% of plant genes are found in insects and 17% are found in humans ¹⁾
    • some plant proteins do behave in ways very similar to neural molecules
    • some plants seem to show synapse-like regions between cells, across which neurotransmitter molecules facilitate cell-to-cell communication
    • many plants have vascular systems that look like they could act as conduits for the “impulses” that they need to transmit throughout the body of the plant
    • some plant cells display what could be interpreted as action potentials—events in which the electrical polarity across the cell membrane does a quick, temporary reversal, as occurs in animal neural cells
    • they can respond to their environment
      • have different signaling for blue, white and red light hence can detect color
      • gravitropism - respond to gravity in terms of growth direction
      • phototropism - respond to gravity in terms of growth direction
      • heliotropism - move leaves throughout the day to face the sun
      • climbing plants, like vines and creepers, use similar mechanisms to respond to touch, clinging and curling around the first object they contact
      • flower depending upon season
      • some use local electrical impulses to trigger carnivorous actions such as leaf closing to capture an insect
    • they can transmit responses to distant parts by propagating action potentials (seems they use calcium ions and glutamate)
      • impulses seem to be used somehow regulate their immune defenses
• brains appear to have evolved to provide homeostatic mechanisms and then an evolutionary advantage as either being a predator, or avoiding being a prey and to make greater use of improved sensory systems and more complex motor systems, and in mating behaviours
• each species has its own sensory system and thus neural networks optimised for these systems to generate their perception of the environment
• invertebrate gut brain
  • the “gut brain” was probably the 1st neural network to evolve, primarily to optimise digestion through muscle contractions, etc
• invertebrate nerve reflex arc nets
  • these are simple neural systems to take sensory inputs from the environments (touch, smell or taste) and then create a reflexive activation of muscle fibres mainly to create movement to avoid dangers or to find food (eg. jellyfish) and further evolved to provide sensorimotor capabilities for environmental awareness and learned behaviours (eg. octopus)
  • evolution of olfaction and taste:
    • critical inputs to search for food, avoid toxins, and detect predators
    • even single celled organisms have the ability to detect chemicals and migrate towards them albeit without neural control
  • evolution of attention and sleep / wake cycles
    • early forms of the reticular formation
    • choosing which to attend to is largely determined by emotions of approach / avoidance systems
• bilateral symmetry invertebrates with neural ganglia at the head end
  • evolved ~650mya eg. worms, arthropods
  • nerve nets curved into a tube to form neural ganglia and a ventral nerve cord
  • HOX genes allowed the evolution of bilateral symmetry in the Bilateria which is mainly of benefit in efficient directed locomotion and thus one end became the head end which would be closest to food
  • also now have the ability to move voluntarily without the requirement of a sensory stimulus to initiate a reflex arc with the help of additional sensory inputs such as smell or sight
    • arthropod “brains” are the supraesophageal ganglion
      • 3 parts:
        • protocerebrum, associated with the eyes (compound eyes and ocelli)
        • deutocerebrum processes sensory information from the antennae
          • antennal lobe - olfaction
          • dorsal lobe - motor control of antennae
        • tritocerebrum - integrates sensory inputs from the previous two pairs of ganglia
      • receives and processes information from the first, second, and third metameres (pre-oral, antenna, ocular segments of the head) and the ventral nerve cord
    • arthropods are made up of segments (as evolved from worms, etc) and each has a segmental ganglia as part of the ventral nerve cord allowing each segment to have some autonomous control
    • further evolution of olfaction and taste:
      • insects have an antennal lobe that functions similarly to the vertebrate olfactory bulb
    • evolution of vision:
      • early light detectors were photo-sensitive cells which just detect the level of light, adding a conical eye cup gave animals a way to assess direction of the light
      • early bilateria had primitive eyes with c and r type opsins
      • by making the opening of the eye cup smaller, a pupil evolved then adding pupillary muscles to adjust size of the pupil allowed optimisation for bright and dark environments
      • the addition of lens(es) allowed the focusing of light to provide much more detail to be detected by a layer of photo-sensitive cells
      • the evolution of different photo-sensitive proteins allowed the development of colour vision
      • early optic neuronal system processing was largely confined to ganglia (and later this became part of the invertebrate brainstem) and whilst this gave an awareness of surroundings it did not provide a “visual representation” of our surroundings as does our visual cortex provides
    • evolution of group behaviours, roles
• vertebrate brain (fish and reptiles)
  • consists mainly of brain stem and cerebellum, with a relatively small limbic system equivalents (telencephalon) and cortex
  • all vertebrate brains possess three major divisions: the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon) ²⁾
    • the embryonic brain neural tube has morphologically or molecularly defined transient segments called neuromeres and named prosomeres, mesomeres and rhombomeres to correspond to each brain division
    • the anatomical boundaries of neuromeres are determined by the expression of Hox genes in a particular zone
  • the ventral nerve cord structure of invertebrates has now been rotated to become the dorsal spinal cord which has resulted in decussation of fibres from right to left and vice versa
  • connection with the older gut / enteric neural system forming the gut-brain axis (GBA) linking emotional and cognitive centers of the brain with peripheral intestinal functions which is modulated by gut microbiome - microbiota and GBA appears to be bidirectional, through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links
  • further evolution of attention and sleep / wake cycles
    • development of the reticular formation in the brainstem including the locus caerulus, pontine and thalamic reticular nuclei
    • further development of the olfactory telencephalon in particular to direct attention to smells
    • further development of emotions (fear, disgust, happy, sad, stress, etc), rewards, approach/avoidance - pituitary / hypothalamus / telencephalon
      • amphibians have an amydaloid complex
  • further evolution of olfaction and taste:
    • development of the olfactory nerves and olfactory bulb with neural connections to the amygdala, orbitofrontal cortex (OFC) and the hippocampus where it plays a role in emotion, memory and learning.
    • land dwelling animals developed olfactory receptors for volatile chemicals rather than water soluble chemicals as with water dwelling animals such as fish
  • evolution of hearing and in some, ability to communicate by sound
    • lampreys were perhaps the 1st to have auditory mechanoreceptor hair cells c430mya
    • 1st cochlear bones evolved c380mya to provide and enclosed environment for the auditory hair cells separate to the environmental water - in land animals, this became elongated, and in mammals coiled, to allow a greater range of frequencies to be heard.
      • different frequency information is coded by distinct neurons that are spatially aligned (tonotopicity)
    • land animals including reptiles and birds also evolved ear drums and thus middle ears with a type of stapes bone (columella) to improve sound detection in air rather than under water
    • NB. fish also utilised these mechanoreceptor hair cells along the length of the body in the “lateral line” as a balance equilibrium system given water impulses are the main impacts on equilibrium and their neural pathways via lateral line and octaval auditory nerves which pass to the medulla are for equilibrium and basic audition from their primitive ears which lack advanced cochlears, rather than for pure hearing
    • brainstem auditory nuclei evolve:
      • 1st order nucleus: the cochlear nucleus in the pons and medulla of the brainstem to receive auditory frequency inputs from the cochlear nerves
        • in fish, the homologue of the cochlear nucleus is the octaval nucleus
        • in reptiles and birds, this evolved into nucleus angularis, nucleus magnocellularis, and nucleus laminaris
        • in mammals, this evolved into a dorsal and ventral nucleus of the cochlear nucleus
      • 2nd order nucleus: superior olive to ascertain where a sound is coming from
        • in fish, this is the secondary octaval nucleus
      • 3rd order nucleus: the lateral lemniscus (NLL)
        • in fish this is the perilemniscal nucleus;
        • in reptiles, birds and mammals this is evolved into sections: dorsal nucleus, intermediate nucleus and ventral nucleus of the lateral lemniscus)
    • the auditory midbrains of vertebrates evolved to have a pair of inferior colliculi with several common features:
      • frequency selectivity is spatially organized (tonotopic map)
      • integrates information from the different auditory nuclei in the brainstem, where different nuclei form parallel auditory processing streams
      • is multimodal in that it takes inputs from other sensory modalities (eg, somatosensory, visual, and electrical senses) which are also integrated
      • in fish, the homologue of the inf colliculus is the torus semicircularis
        • the inhibitory circuits were present in fish and thus likely to be essential for vertebrate hearing and appear to be critical in shaping the response properties of the torus semicircularis neurons ³⁾
    • auditory centres of the thalamus evolve
      • fish appear to have an auditory response in the central posterior thalamic nucleus
    • higher auditory cortical centres evolve
      • fish appear to have two auditory centres (also receive information from their lateral line), the central zone (Dc) of the caudal dorsal telencephalon and in the ipsilateral dorsomedial telencephalon ⁴⁾
      • teleosts (ray-finned fish) have sensory afferents to the pallium, however, the morphology of the teleost pallium is very different from that of tetrapods, as the developmental processes are different (evagination in tetrapods versus eversion in teleosts) and have a posterior tuberculum and preglomerular complex which function similar to parts of the tetrapod thalamic regions but are not present in tetrapods, however, a large posterior tuberculum is present in jawless vertebrates (lampreys), cartilaginous fishes (sharks and manta rays), lungfish, and amphibians ⁵⁾
        • teleosts share with other vertebrates the thalamus proper, the habenula, and the prethalamus
        • teleosts and amphibians have prethalamic structures of the intermediate (I), the ventromedial (VM), and the ventrolateral (VL) thalamic nuclei which are not present in mammals
        • the auditory “thalamic” nucleus (CPo) of teleosts projects to the amygdala (Dm) and to the hippocampal (Dl) division somewhat analogous to mammalian pathways ⁶⁾
      • amphibians: sensory projections from the thalamus (Th) mainly terminate in the subpallium (SPa; ventral telencephalon containing the striatum)
      • in birds, several different thalamic nuclei convey sensory information to the pallium (Pal; dorsal telencephalon containing the cortex in mammals) in a modality-specific manner
      • mammalian thalamocortical pathway to the primary auditory cortex
  • further evolution of visual systems and gaze
    • in animals where the head was free to move, a gaze mechanism and 3D visual spatial map system evolved - the optic tectum or optic lobe (homologous to the mammalian superior colliculi) - and in mammals with loss of visual cortex they can still utilise the superior colliculi to provide “blindsight” ⁷⁾
  • sharks:
    • can hear prey at 1km, smell and feel it at 100m, perceive its electrical activity at 50cm, taste it before it goes into the mouth but can only see a blurry image at very short range as it goes into its mouth, although a great white shark will chase the shadow of a drone
  • barn owls:
    • evolved a very accurate 3D auditory spatial map in their inferior colliculus / tectum equivalent in the brainstem allowing them to hunt in pitch black conditions
• mammalian brain
  • expanded the limbic system and periventricular layers
  • oRG cells are common in most mammals notable exception are rodents (which also have a large deletion in ASPM gene and perhaps need a smaller head to fit into small holes)
  • further evolution of hearing
    • outer ear / pinna to improve ascertainment of direction of sounds especially from above as well as to funnel sound to the ear drum
    • medial geniculate nucleus evolved with neurons specific to various sound frequencies designed to detect changes in sounds to alert for prey or predators
    • 2 small synapsid jaw bones became the malleus and the incas to further improve sound transmission in the middle ear
    • further elongation and coiling of the cochlear
    • much greater sound information now detected and being processed and hence expansion of the auditory cortex components and allow interpretation of species vocalisation
    • in bats, dolphins, evolved echolocation
  • further evolution in attention
    • top-down attention - ability to voluntarily select various sensory inputs to attend to is much improved thanks to expansion of the prefrontal cortex
• primate brain
  • expanded the outer cortical layers
  • tree dwelling primates reduced olfaction sophistication as they relied more upon color vision to ascertain ripe fruits and on sharp 3D vision to watch for raptors
• human brain
  • hominins separated from chimps 6mya
  • further expanded areas such as the prefrontal cortex to provide improved cognitive or executive control and allow abstract thought and future thought
  • brain size increased 3x fold 200,000yrs ago compared with other primates which may be due to genetic changes such as:
    • duplication of chromosome 1 NOTCH2 gene into 4 versions instead of 1 in chimps (regulates division of stem cells in fetuses such as oRG cells)
    • ASPM, CDK5RAP2, CEP63, WDR62 gene mutations all can cause microcephaly
      • ASPM knockout causes microcephaly by causing a shift in apical progenitors into the outer sub ventricular zone and changes the type of stem cell to be less proliferative, reducing cortical surface area but retains cortical thickness and cryptoarchitecture ((Nature 2018 Johnson et al)
    • Human Accelerated Regions
      • >3000 HARs which help to make us different to mammals but not yet clear which have roles in brain evolution
      • HAR426 mutation may cause autism - this HAR connects to gene CUX1 and related gene CUT which have roles in determining complexity of dendrites in neurons especialy in the most upper layers of neurons which evolved last

• see https://www.youtube.com/watch?v=hSHNSw95Zzw
• after 16wks gestation, unlike mice, human fetuses develop a discontinuous glial scaffold with the outer layers of the cortex being produced by outer radial glia cells and not by ventricular glia cells and the initial ventricular glia cells become transformed into truncated radial glial cells
  • 3 main types of radial glia stem cell types in humans:
    • ventricular glia cells (vRG)
      • line the ventricles and gain growth factors etc from the CSF and reach the pia
    • outer radial glia cells (oRG)
      • normally, each outer radial glia cell in human fetuses normally generate 700-1000 upper and lower layer neurons (in mice, these cells only produce 20-40 neurons)
      • as with stem cells, oRG cells selectively express LIFR/STAT3 signalling which promotes self-renewal
      • oRG cells in mice line the ventricles where they can receive trophic factors from the CSF, however, in primates, these cells have moved away from the ventricles and no longer able to access the CSF but instead created their own signalling pathways and their own growth factors, reach the pia surface layer, creating their own niche for self-renewal and expansion, and thus are able to undergo prolonged and massive proliferation.
      • as with astrocytes, microglia and some other cells, these cells have AXL receptors making them vulnerable to zika virus during early fetal life which may result in microcephaly
      • these are probably the cells causing glioblastoma multiforme in adults
    • truncated radial glial cells (tRG)
      • line the ventricles and gain growth factors etc from the CSF but do not reach the pia but instead are confined to the periventricular layer