Brain Embryonic Development, Infancy, and Childhood Development

Brain development begins prenatally, continues through infancy, childhood and adolescence, producing [growth refinements] of the “self,” which interacts with mental images to produce Edelman’s “remembered present” and “dynamic core,” resulting in the emergent property of consciousness. My understanding of consciousness uses the concepts of proto-self, core self and autobiographical self as enunciated by Damasio.

Network of neurons formed during embryonic development

As axons extend to their destinations during embryonic development, growth cones seek the proper genetically and structurally determined area with fields of awaiting dendrites. A growth cone makes specific contact with a dendrite stochastically. An approximate 3:1 superabundance of synapses is formed. Via experience on a use-it-or-loose-it basis, the neural network is formed over time with strengthen synapses and atrophied synapses.

Research study — Brain and Spinal Cord Cell Profiling with Barcoding

Research study — Synaptic Transmission Controls Radial Migration of Neurons

Research study — Prefrontal Cortex Development of Diverse Functional Cells

Research study — Synapse Formation, Neurons, Glial Support Cells

Research study — Brain Organization comparison between Human and Nonhuman Primates

Research study — Retrospect: The Selfish Gene

Research study — Oligodendrocyte Precursors Migrate along Vasculature in Developing CNS

Research study — Allen Institute for Brain Science, Transcriptional landscape of the prenatal human brain

Research study — Embryonic Development via Enhancers and their Regulatory Landscapes

Research Study — Epigenetics in Human Embryos

Research Study — Nervous System Reprogrammed from One Cell Type to Another — Neurons specialize into an astonishing diversity of classes. Suites of factors can convert non-neuronal cells into induced neuronal cells showing class-specific features.

Research study — Ribosome Protein Mutations can cause Tissue-Specific human disease

Research study — Neural Crest Cell Development, Schwann Cells

Research study — ENCODE encyclopedia of DNA elements in the human genome

Research study — Brain Development Epigenomic Reconfiguration

Research Study — Motor Neurons Relay Neural Commands to Drive Skeletal Muscle Movements

Research Study — Embryonic Development of Brain

Embryonic development

Overall synopsis. Neural structures form in the early embryo (genetics influence begins). Hox genes. Neurons form, migrate, axons form, growth cones, chemitaxis guided by structure, non-precise contact, synapses form, neural activity (environmental influence begins), “use it or loose it” begins in early fetus and continues postnatal.

As an example, hippocampus mediates the formation of long-term declarative memory dispersed widely in the synapses of the cortex. Most people cannot remember earlier than age three. Critical time for language.

One particularly well-conserved class of transcription factors, the Hox genes, is important in establishing and maintaining the regional identity of cells and tissues along the anterior-posterior axis of vertebrates throughout the hindbrain and spinal cord. (Sanes; Development of the Nervous System, 55)

Neural development mechanisms are conserved in different organisms. Molecular basis of neural development in vertebrates derives from organisms such as the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. (Kandel; Principles of Neural Science, 1021)

Research Study — Sequential Transcriptional Waves direct the Differentiation of Newborn Neurons

Research Study — Cortical Neuron Development by GABAergic Projections

Research Study — Embryonic Development of Cortical Microcircuits via Chandelier Interneurons

Research study — Synaptogenesis induced by GABA in the Developing Mouse Cortex

The pyramidal cell layer of the hippocampus forms quite early in the human brain. (Andersen; Hippocampus Book, 116)

For pathfinding and target recognition, pioneer neurons provide a template by an early-formed projection. (Andersen; Hippocampus Book, 127)

Most aspects of gross cortical structure, such as cell numbers and location, are in place at the time of birth in the human infant. More detailed aspects of cortical structure such as synaptic density, strength of connectivity, and glucose uptake, show prolonged postnatal development. (Parasuraman, Attentive Brain; Johnson; Developing Attentive Brain, 428)

Neurons in the developing cortex are generated from radial glial cells that function as neural stem cells. These epithelial cells line the cerebral ventricles and generate intermediate progenitor cells that migrate into the subventricular zone (SVZ) and proliferate to increase neuronal number. The developing human SVZ has a massively expanded outer region (OSVZ) thought to contribute to cortical size and complexity. (Neocortex Outer Region Subventricular Zone Development)

Early Development of the Brain's Three Major Divisions: Forebrain, Midbrain, Hindbrain. (Pinel; Anatomy of Human Brain, 58)

Five stages in the embryonic development of the cerebral cortex from the wall of the neural tube. - (illustration) (Changeux; Neuronal Man, 197)

Brain is made up of 10¹¹ cells with at least 10¹³ connections. Each cell has an intricate regulatory biochemistry constrained by a particular set of genes. Cells come together during morphogenesis and exchange signals in a place-dependent fashion to make a body with enormous numbers of control loops, all obeying the homeostatic mechanisms that govern survival. (Edelman; Bright Air, 166)

At one time or another in their careers all neurons are gypsies -- moving to their final positions on other cells. Network of the brain is created by cellular movement during development and by the extension and connection of increasing numbers of neurons. Developmental driving forces provided by cellular processes such as cell division, movement and death. In some regions of the developing nervous system up to 70 percent of the neurons die before the structure of the region is completed. In general, uniquely specified connections cannot exist. Neurons generally send branches of their axons out in diverging arbors that overlap with those of other neurons. Arbors of dendrites on recipient neurons await the axon growth cones of incoming neurons. (Edelman; Bright Air, 23-25)

Sonic hedgehog (SHH) influences CNS development

Sonic hedgehog (SHH) exerts a powerful influence on the development of the central nervous system. (Kandel; Principles of Neural Science, 1027)

Signaling pathway is triggered by the interaction of sonic hedgehog protein with a heterodimeric receptor complex. (Kandel; Principles of Neural Science, 1027)

No Adult Neurogenesis in Most Brain Areas

Once the developmental period of neurogenesis is complete, most areas of the brain do not generate new neurons, even after damage. (Sanes; Development of the Nervous System, 85)

Certain regions of the brain, the hippocampus and the olfactory bulb, continue to add new neurons throughout life. (Sanes; Development of the Nervous System, 85)

Continual addition of neurons in regions such as the hippocampus and olfactory bulb may allow for greater plasticity in these specific brain circuits. (Sanes; Development of the Nervous System, 85)

Research study — Neural Development of Spines

Neuronal connections not precisely specified in the genes

Connections among cells are not precisely specified in the genes of the animal. (Edelman; Bright Air, 23)

Precise point-to-point wiring cannot occur; the variation is too great for the information stored in the genome. (Edelman; Bright Air, 25)

The dendritic spines studding the surface of CA1 dendrites exhibit a broad range of size and morphological complexity. (Andersen; Hippocampus Book, 136)

Establishing the initial connections, much randomness, axon terminals and dendrites that happen to be in the same vicinity, form synaptic connections. (LeDoux; Synaptic Self, 73)

Behavior of the growth cone, genetic cost is modest, great variability in the arrangement of the first contacts with the target; very little precision in the assembly of the network. (Changeux; Neuronal Man, 215)

Brain is an example of a self-organizing system. (Edelman; Bright Air, 25)

Developmental driving forces provided by cellular processes such as cell division, movement and death. (Edelman; Bright Air, 25)

Network of the brain is created by cellular movement during development and by the extension and connection of increasing numbers of neurons. (Edelman; Bright Air, 25)

In some regions of the developing nervous system up to 70 percent of the neurons die before the structure of the region is completed. In general, uniquely specified connections cannot exist. (Edelman; Bright Air, 25)

Neurons generally send branches of their axons out in diverging arbors that overlap with those of other neurons. (Edelman; Bright Air, 25)

Arbors of dendrites on recipient neurons await the axon growth cones of incoming neurons. (Edelman; Bright Air, 25)

Research study — Interneuron Developent Cell Death Intrinsically Determined — Either a cell-autonomous or population-autonomous mechanism could explain why cell death occurred at a constant rate across broad range of interneuron transplant sizes.

Research study — Embryonic Development of Cortical Columns

Neural migration

Cortex of the brain is formed by migration of neurons from a 'germinal zone' close to the ventricles deep in the brain. Migration is guided by glial cells, which extend radial fibers along the route. - (diagram) (Zeman; Consciousness, 202)

Crawling of the neuroblast along the radial glial scaffold. (Sanes; Development of the Nervous System, 73)

Crawling along the glial trail, the young neurons find their way to their target. (LeDoux; Synaptic Self, 70)

Pioneer axons navigate in a simpler environment. As the brain matures, more axons are added, and the weave becomes more intricate. As later axons navigate, they are aided by pathways laid down by earlier axons. Rich tapestry of the brain wiring is accomplished by successive addition of new fibers that add complexity in a stepwise fashion. (Sanes; Development of the Nervous System, 111)

Growth cones

Under an electron microscope, a growth cone looks somewhat like a tiny amoeba. When growth cones reach target, movements suddenly cease. Immobilized cone is transformed in a few hours into a nerve terminal, gradually takes the appearance of a mature synapse. Behavior of the growth cone, genetic cost is modest, great variability in the arrangement of the first contacts with the target; very little precision in the assembly of the network. Epigenetic mechanisms tune it up, create the final set of neural connections. (Changeux; Neuronal Man, 213-215)

Activity leads to an increase in synaptic complexity

Neural Activity leads to an increase in synaptic complexity. Donald Hebb, 1949, 'Cells that fire together wire together'. Activity can induce the formation of new synaptic connections. Activity helps define the demarcation between areas of the cortex. Axons from the visual thalamus spread into the auditory cortex area, and vice versa, early in life. As development proceeds, the stray connections are pruned back. Activity does not produce wholesale rewiring of the brain, instead it makes relatively minor adjustments that make individual brains different. (LeDoux; Synaptic Self, 77-79)

Activity only prevents the elimination of synapses; "use it or lose it." (LeDoux; Synaptic Self, 75)

Neurotrophins - promote survival and growth of neurons. Neurotrophins released from postsynaptic cell, diffuse backward, taken up by presynaptic terminals; branch and sprout new synaptic connections. (LeDoux; Synaptic Self, 81)

Subcortical circuits are more likely to be hardwired than cortical ones. (LeDoux; Synaptic Self, 89)

Perception of facial expressions of emotion is performed by a species-specific face perception module. (LeDoux; Synaptic Self, 89)

Both Genetics AND Environment influence Neural Network Development

People are different as a result of their genetics and their environmental influences during development. Even identical twins with identical genetics have different neural networks as a result of their different experiences during development. Identical twins have different fingerprints for a completely different reason.

Identical twins develop from the division of the same fertilized ovum; genetically identical. Variability in neural organization of identical twins. - (illustration) (Changeux; Neuronal Man, 206-208)

Experience, which is never the same from one individual to another, leads to a different neuronal and synaptic topology. (Changeux; Neuronal Man, 247)

Well-defined structure for the neocortex and its connections to subcortical bodies that is replicated across individuals and not modified on a gross scale by experience. (Koch, Neuronal Theories; Van Essen; Dynamic Routing Strategies, 299)

Research study — Genetic Variants and Functional Effects in Human Traits

Motor neurons of the spinal cord share a common morphology, chemistry, physiology, and circuitry, yet they are distinctly specified molecularly so that they can connect with particular presynaptic partners and postsynaptic muscles. (Sanes; Development of the Nervous System, 87)

Core consciousness and the generation of core self is under strong gene control. The genome puts in place the appropriate body-brain linkages. Autobiographical self develops and matures under the looming shadow of an inherited biology. However, unlike the core self, much will occur in the development and maturation of the autobiographical self that is regulated by the environment. (Damasio; Feeling of What Happens, 229)

Aspects of the body's physical structure and function are engraved in brain circuitry, from early development, and generate persistent patterns of activity. (Damasio; Self Comes to Mind, 93)

The "self" is not constructed, it is selected from preexisting possibilities. (LeDoux; Synaptic Self, 74)

Referential memory represents that which has accrued during development and throughout a single lifetime. (Llinás; I of the Vortex, 181)

Research study — Synapses Pruned by Microglia

Consciousness emerges gradually in infants

Developmental psychologists postulate that consciousness emerges gradually during the second year of human life and culminates at about age 2 with the gaining of awareness of the self as an entity. (Hobson; Consciousness, 99)

Infantile amnesia

Infantile (childhood) amnesia refers to the lack of declarative memory before about 3 years of age. The hippocampus and its associated circuitry have not developed sufficiently to form declarative memories.

Childhood amnesia may be due to the lack of neurological development of the infant brain, preventing the creation of long term or autobiographical memories. Two key structures in the neuroanatomy of memory, the hippocampus and prefrontal cortex, do not develop into mature structures until the age of three or four years. These structures are known to be associated with the formation of autobiographical memories of the type notably missing from adult recollection of early childhood. (Wikipedia)

Critical times for learning

Special times for learning - critical or sensitive periods - narrow time span in early life - learn a second language after puberty. (LeDoux; Synaptic Self, 94)

Learning is a lifelong process - early years are crucial - foundation for subsequent learning - extensive plasticity in early life - synapses do not stop changing. (LeDoux; Synaptic Self, 96)

Research study — Development of Large-Scale Functional Brain Networks in Children

Close nurturing during early childhood

Our basic cognitive capacities; the emotions we feel; the thoughts we have and the beliefs, desires and intentions we form; our ability to communicate with others, both nonverbally and verbally, and our ability to understand what others are thinking and feeling; can only emerge in the context of the close nurturing relationships that a child experiences with his caregivers. (Greenspan; First Idea, 102)

Neural network and Sexual Orientation

In many mammalian species the brain is inherently feminine. Masculine characteristics of structure and function are imposed on the developing central nervous system by the action of testicular hormones during a critical period. (Kandel; Principles of Neural Science, 1131)

Testosterone is often thought of as a male sex hormone and estrogen and progesterone as female sex hormones. In reality, each sex has a particular balance of several hormones, although testosterone does predominate in males and estrogen or progesterone in females. (Kandel; Principles of Neural Science, 1136)

Genetics and environment produce the neural network.

Sex differences of organisms produce differences in neural network in development.

Forebrain and limbic system are richly connected, and thoughts of the opposite sex stimulate the limbic.

Men are stimulated by thoughts of women, and conversely.

Generally, men are attracted by a curvy female body with amble breasts and noticeable hips. These features are likely to be a primitive indicator of reproductive fitness. I believe that sexual orientation is innate; I can remember even as a preschooler my pleasant emotional interest in seeing adult women with ample breasts and hips.

Sometimes the neural network’s sexual orientation development is incompatible with the sex of the body. The result is homosexuality. Research is continuing on this topic, but biological mechanisms of homosexuality are currently not well understood. My current belief is that sexual orientation is established during prenatal neural network development.

Formation of Major Subdivisions of Brain

(paraphrase of Purves, et al.; Neuroscience, 510-533)

Generation of cortical neurons during gestation, Cortical layers - (diagram) (Purves; Neuroscience, 519)

Migration is a ubiquitous feature of development that brings cells into appropriate spacial relationships. Migration of postmitotic neuroblasts in the fetal brain. (Purves; Neuroscience, 520)

Radial migration in the developing cortex - (diagram) (Purves; Neuroscience, 522)

Stereotyped movements bring different classes of cells into contact with one another, thereby constraining cell-cell signaling to specific times and places. (Purves; Neuroscience, 523)

Cortical projection neurons, interneurons, astrocytes and oligodendroglia were probably not derived from the same precursor pools. (Purves; Neuroscience, 524)

Mosaic of transcriptional regulators whose expression and activity is restricted to various domains in the ventral forebrain orchestrates the long distance migrationn of distinct cell types. (Purves; Neuroscience, 524)

Growth cones are highly motile structures that explore the extracellular environment. (Purves; Neuroscience, 527)

Basic structure of growth cones - (diagram) (Purves; Neuroscience, 529)

Semaphorins, repulsive cues, either bound to cell surface or secreted; receptors (plexins and neuropilin) found in growth cones. (Purves; Neuroscience, 532)

Growth cone interactions with environment - (diagram) (Purves; Neuroscience, 533)

(end of paraphrase)

Visual development

Area V1 develops so that broad features, such as which region corresponds to the fovea, are probably laid down by genes. Finer details are likely to be modifications made during input from the eyes, perhaps by whether the firing of neurons are correlated. Almost as many neurons project backward from V2 as project forward from V1. The forward projection goes heavily into layer 4 of V2, whereas the backward projection to V1 avoids layer 4 altogether. At least twenty distinct visual areas have been identified, plus about seven more that are partly visual. (Crick; Astonishing Hypothesis, 145-149)

Research study — Visual Cortex Functional Microcircuits

Oral language development

An infant begins to babble and gradually over a few years learns to talk and mimic and converse with persons around her to produce oral speech and conversation. This learning process likely involves the formation of procedural memory in Broca’s area in the subcortical parallel circuitry through the basal ganglia and through the auditory cognitive sensory area. In this way, a child hears other person's speech and compares it with their own vocalizations and successively attempts to mimic the sounds that are heard, thereby gradually establishing procedural memory for FAPs vocalizations involving muscular movements of the throat and vocal apparatus.

Research Study — Speech Sensory–Motor Transformations occur Bilaterally

Research Study — Phonetic Feature Encoding in Cortex

Research Study — Speech Organization in Cortex — Production of fluent speech requires the precise, coordinated movement of multiple articulators (for example, the lips, jaw, tongue and larynx) over rapid time scales. We found speech-articulator representations that are arranged somatotopically on ventral pre- and post-central gyri, which were coordinated temporally as sequences during syllable production.

Language understanding and development

When a young child converses in playtime activities, their conversation of language becomes descriptive of the activities in which they are engaged. In this way they synaptic circuitry of Wernicke's area and the pathway of auditory circuitry, subcortical basal ganglia parallel pathways, and other cognitive pathways, are involved and gradually form synaptic connections of procedural memory for language understanding in the Wernicke's area. This formation of synapses in the Wernicke's area is greatly facilitated by school time studies.

Musical intelligence development

Mozart had natural talent for music that was recognized during his childhood and trained by his father. Mozart had an unusual musical intelligence. His brain must have been genetically structured in a way that made music easy for him. As an adult, he could compose and write a musical composition from beginning to end without having to review and make corrections. Most ordinary people could struggle indefinitely and never succeed in composing a pleasing musical composition.

Manual skills development

Development of manual skills such as riding a bicycle involves the formation of network of synapse enhancement through the premotor cortex, motor cortex, basal ganglia parallel pathways, cerebellum, and spinal reflex circuitry. Each manual skill is represented as a network off hierarchical Fixed Action Patterns (FAPs).

Excerpts from science experts

Genetic basis

Human genome, ~20 thousand genes; human cerebral cortex, ~10¹⁵synapses. (Changeux; Neuronal Man, 206)

Humans are born with a brain whose maximum number of cells is already fixed. Diversification through recombinations within neuronal assemblies, followed by selection through resonance. Nervous system is unusual in that its total number of neurons is fixed at birth. Neurons that are destroyed after birth are never replaced. Axons and dendrites preserve a remarkable capacity to regenerate even in the adult. (Changeux; Neuronal Man, 277-278, 282)

Thalamocortical, Subcortical development

Thalamocortical activity along with parallel activity in the basal ganglia loops begins prenatally and continues uninterrupted until brain trauma or death.

Both genetics and environment influence brain development and the self. The relationship of a child with caregiver in infancy and early childhood has a dramatic effect on brain development and the self. ( Greenspan; First Idea, )

Development of the human brain continues long after birth. Most synapses of the cerebral cortex are formed after birth. Intimate association of growth and epigenesis and their alternation over time. System becomes more and more ordered as it receives instructions from the environment. Epigenetic selection acts on preformed synaptic substrates. To learn is to stabilize synaptic combinations and to eliminate the surplus. (Changeux; Neuronal Man, 242, 249)

Growth of axonal and dendritic trees is innate; the selective stabilization of synapses defines acquired characteristics. The 10 thousand or so synapses per cortical neuron are not established immediately. They proliferate in successive waves from birth to puberty in humans. With each wave there is a transient redundancy and selective stabilization. The result is a series of critical periods when activity exercises a regulatory effect. (Changeux; Neuronal Man, 248-249)

Consciousness begins

When does consciousness begin? We all spend a very significant amount of time in a very REM-like state before we were born. Embryologists can see eye movements in fetuses only twenty weeks old. In the womb, brain circuits are laid out and tested by an automatic process that arises as soon as the networks of nerve cells are first formed. This self-organization is a property of all complex systems to create order out of chaos. At some point in early life, the brain network has enough images and thoughts to have conscious awareness. Add a few more and it has enough to be aware that it is aware. Once we have self-reflective awareness, we are fully conscious. Self-reflective awareness is the essence of what we imply by the term consciousness. (Hobson; Dreaming as Delirium, 141-142)

Learning

Special times for learning - critical or sensitive periods - narrow time span in early life - learn a second language after puberty. Learning is a lifelong process - early years are crucial - foundation for subsequent learning - extensive plasticity in early life - synapses do not stop changing. (LeDoux; Synaptic Self, 94-96)

Neocortical areas have six layers. (LeDoux; Synaptic Self, 76)

NMDA receptors. (LeDoux; Synaptic Self, 81)

Evolutionary psychology - natural selection of mental functions(LeDoux; Synaptic Self, 84).

Edelman’s Theory of neuronal group selection (TNGS) or Neural Darwinism

Theory of neuronal group selection (TNGS) or Neural Darwinism. (1) Developmental selection, (2) Experimental selection, (3) Reentrant mapping. (Edelman; Universe of Consciousness, 83)

During embryonic development, neurons extend branching axons via chemosensory guidance, forming extensive synapse patterns in each person. Later activity in the neural network "prunes" the unused synapses. (Edelman; Universe of Consciousness, 83)

Neurons strengthen or weaken their synaptic connections according their individual patterns of electrical activity: Neurons that fire together wire together. (Edelman; Universe of Consciousness, 83)

References for Neural Development

Sanes, et al, Development of the Nervous System – excellent textbook, easy reading, lots of informative diagrams.

Gilbert, Developmental Biology -- an excellent textbook with lots of diagrams and lots of informative discussion of all the traditional developmental biology topics.

Purves, Neuroscience -- Also a good reference on brain development.

Link to — Consciousness Subject Outline