Chapter 9 - Development of the Nervous System

In general, the sensory and motor areas of cerebral cortex achieve maturity before the _______________ areas.

Cognitive

Zygote

Fertilized egg; a single cell formed by the amalgamation of an ovum and a sperm. It divides into two two daughter cells which these two diving into four, eight and so on until a mature organism is produced.

When does myelination of motor areas occur in human development?

Follows the myelination of sensory sensory areas which occurs in the first few months after birth - motor areas are after.

What is cell migration in the developing neural tube considered to be of?

Two kinds: Radical migration and tangential migration.

What are the three things other than cell multiplication which much occur in human development?

1) Cells need to differentiate; some becoming muscle cells, multipolar neutrons, glial cells, etc. 2) Cells must make their way to appropriate sites and align themselves with cells around them to form structures. 3) Cells must establish appropriate functional relations with other cells.

What are the stages of neurodevelopment?

1) Induction of the neural plate. 2) Formation of the neural tube. 3) Neural proliferation. 4) Neural migration. 5) Neural aggregation. 6) Growth of neural processes (axonal and dendrites). 7) Formation of synapses. 8) Neuron death and synapse rearrangement.

What are the two general types of experience on brain development?

1) Permissive 2) Instructive

What are the two methods by which developing cells migrate?

1) Somal translocation 2) Glia-mediated migration

What triggers the genetic programs that cause apoptosis in developing neurons?

1) Some developing neurons are genetically programmed for early death once they have fulfilled their functions, such as groups of neurons dying together in the absence of any obvious external stimulus. 2) Some developing neurons die because they fail to obtain the life-preserving chemicals that are supplied by their targets.

What are the four types of cognitive functions that have been linked to the prefrontal cortex?

1) Working memory - keeping relevant information accessible for short periods of time while completing a task. 2) Planning and carrying out sequences of actions. 3) Inhibiting responses that are inappropriate in the current context but not in others. 4) Following rules for social behaviour.

What are the five phases of neural development?

1) induction of neural plate 2) neural proliferation 3) migration and aggregation 4) axon growth and synapse formation 5) neuron death and synapse rearrangement

Autism Spectrum Disorder (ASD)

A complex neurodevelopmental disorder characterized by a reduced capacity for social interaction and communication and restrictive and repetitive patterns of behaviour, interests or activities. Difficult to define because cases differ so greatly. Almost always apparent before age 3, but typically doesn't increase in severity after that age. Two core symptoms are: 1) Reduced capacity for social interaction and communication. 2) Restricted and repetitive patterns of behaviour, interests or activities. 75% are male, and many suffer from intellectual or learning disabilities, and likely to suffer from epilepsy. Older mothers are more likely to give birth to a child with ASD but the probability of a young mother under 30 giving birth to a child with ASD increases if the father is over 40. Its MAIN early warning sign is a delay in the development of social interaction with specific signs such as a decline in eye contact between 2-6 months, no smiles or happy expressions by 9 months, and no communicative gestures such as pointing or waving by 12 months. The most prevalent neurodevelopmental disorder. Estimates are 1 in every 68 births. Intensive behavioural therapy can help improve the lives of some individuals, but its often difficult for them to live independently.

Totipotent

A fertilized egg capable of developing into any type of body cell (bone, heart, skin, neuron). After generations of new cells are created by cell division the newly created cells tend to be specialized and are no longer totipotent.

What kind of disorder is ASD?

A heterogenous neurodevelopmental disorder. Heterogeneous in the sense that affected people may be severely impaired in some aspects but typical or superior in others.

Williams Syndrome

A neurodevelopmental disorder characterized by intellectual disability, accompanies by preserved language and social skills. Like ASD, its associated with intellectual disability and heterogeneous pattern of abilities and disabilities. BUT in contrast, people with this syndrome are sociable, empathetic and talkative. It occurs in 1 in 7,500 births. The language abilities in the syndrome has attracted attention, because even though they display a delay in language development and deficits in adulthood, their skills are remarkable considering their characteristically low IQ which is around 55. Their cognitive strengths aren't just limited to language, they are also often musically gifted. While most can't read music, they have near perfect or perfect pitch and rhythm. They also tend to show more interest in and emotional reaction to music. Another strength is their near typical abilities in recognizing faces, although whether they process faces in a typical manner is under debate. Their cognitive deficits are severe attentional problems, spatial abilities which are worse than those with comparable IQs such as having difficulty remembering the locations of a few blocks on a test board. Their space related speech is poor and their ability to draw objects is almost nonexistent. It is associated with many health problems. Heart disorders resulting from the mutation in a gene on chromosome 7 which controls the synthesis of elastin - a protein that imparts elasticity to many organs and tissues including the heart. The gene is absent from one of the two copies of chromosome 7 in 95% of people with the syndrome. Apparently from an accident of reproduction that deleted an entire segment of chromosome 7, a segment which included the elastin gene and around 25 others. Brain differences are decreases in basal ganglia volume, neural correlates of the cortex and underlying white matter, cortical thinning at the boundary of the parietal, occipital lobes and the orbitofrontal cortex. But there is thickness in the cortex in the superior temporal gyrus.

Critical Period

A period during development in which a particular experience must occur for it to influence the course of subsequent development. Ex: Language

Elastin

A protein that imparts elasticity to many organs and tissues including the heart.

Neural Plate

A small patch of ectodermal tissue on the dorsal surface of the vertebrate embryo, from which the neural groove, the neural tube, and, ultimately, the mature nervous system develop. Begins 3 weeks after conception, which is the tissue that is destined to develop into the human nervous system and is seen as the neural plate. The ectoderm is the outermost of the 3 layers of embryonic cells followed by the mesoderm and endoderm. Its development is induced by chemical signals forming an area of the underlying mesoderm layer.

Neural Crest

A structure situated just dorsal to the neural tube. It is formed from cells that break off from the neural tube as it is being formed. Crest cells develop into the neutrons and glial cells of the peripheral nervous system in addition to many other cell types in the body, with many having to migrate over considerable distances.

Growth Cone

Amoebalike structure at the tip of each growing axon or dendrite that guides growth to the appropriate target. Extends and retracts fingerlike cytoplasmic extensions called filopodia, as if they're searching for the correct route.

Sensitive Period

An interval of time during development when an experience can have a greater effect on development if it occurs during that interval, as opposed to outside the interval.

How does synaptogenesis in the prefrontal cortex occur?

At a relatively steady rate, reaching maximum synapse density in the second year.

What role to astrocytes play in synaptogenesis?

Besides providing higher levels of cholesterol, they play an extensive role in processing, transferring and storing information supplied by neurons.

Multipotent

Capable of developing into different cells of only one class of cells (ex: different kinds of blood cells). As an embryo develops, new cells become more and more specialized, eventually developing into cells of only one class.

Apoptosis

Cell death that is actively induced by genetic programs; programmed cell death. In apoptotic cell death, DNA and other internal structures are cleaved apart and packaged in membranes before the cell breaks apart. These membranes contain molecules that prevent inflammation, with apoptosis removing excess neurons in a safe, neat, and orderly way. The dark side is if the genetic programs for cell death is blocked the consequence can be cancer. If the programs are inappropriately activated, the consequence can be neurodegenerative disease.

Pluripotent

Cells that can develop into many, but not all, classes of body cells. It is after newly created cells become specialized and are no longer totipotent.

Unipotent

Cells that can develop into only one type of cell. Most developing cells become this, such as bipolar neurons.

Stem Cells

Cells that have an almost unlimited capacity for self-renewal and the ability to develop into many different types of cells. Cells that meet two specific criteria: 1) The near unlimited capacity for self-renewal if maintained in an appropriate cell culture 2) Ability to develop into many different kinds of cells - either totipotent, pluripotent or multipotent

What is the complex patter of proliferation in part controlled by?

Chemical signals from two organizer areas in the neural tube: 1) the floor plate which runs along the midline of the ventral surface of the tube 2) the roof plate which runs along the midline of the dorsal surface of the tube

Neurotrophins

Chemicals that are supplied to developing neurons by their targets and that promote their survival. NGF - Nerve Growth Factor is the first neurotrophin discovered. They promote the growth and survival of neurons, functions as axon guidance molecules and stimulate synaptogenesis.

Perseverative Error

Children tend to make this error between 7-12 months old. Found in Piaget's studies. The tendency to continue to make a formerly correct response that in currently incorrect.

New neurons that are added to the hippocampus of an adult mammal are created near the _______________ gyrus.

Dentate

What are the cells of the neural plate often referred to as?

Embryonic stem cells.

Permissive Experiences

Experiences that permit the information in genetic programs of brain development to be expressed and maintained. A type of experience on brain development.

Why do stem cells have an almost unlimited capacity for self renewal?

From the fact that when a stem cell divides, two different daughter cells are created: one that eventually develops into some type of body cell and one that develops into another stem cell. But they don't last forever even though they keep dividing because eventually errors accumulate.

Genetic Basis of ASD

Genetic factors influence ASD development, with siblings having about. a 20% chance of being diagnosed with the disorder. Above the rate in the gen.population, but well below the 50% chance that would be expected if ASD was caused solely by a specific dominant gene. If one Mono twin is diagnosed, the other has a 60% chance, which suggests that ASD is triggered by several genes interacting with the environment. Several dozen genes have been implicated, and in less than 5% of cases there is a single gene mutation that can account for the disorder. It may not be entirely neural, there is interest in the role of glial activity in its development. Its suggested that there are underlying alterations to some neural structures but not others, with variations in the underlying neural correlates. Some studies show differences in the cerebellum, amygdala, and frontal cortex.

Radial Glial Cells

Glial cells that exist in the neural tube during the period of neural migration and that form a network along which radial migration occurs. Some radical glial cells are stem cells. And many eventually develop into neurons. They have a role in neurodevelopment.

What do developing neurons need high levels of during synapse formation?

High levels of cholesterol. That extra level is supplied by astrocytes.

Adult rats living in enriched environments produced 60% more _______________ neurons.

Hippocampal

Where does substantial neurogenesis occur in adults?

Its been observed in the striatum and the hippocampus. The number of new neurons added to the adult human hippocampus is substantial, with an estimated 700 per day per hippocampus.

When does myelination of sensory areas occur in human development?

In the first few months after birth.

Where does cortical thinning occur first in the human brain?

In the primary sensory and motor areas, progressing to secondary areas and culminates in association areas.

Where does most cell division in the neural tube occur?

In the ventricular zone.

How long does the myelination of the prefrontal continue in human development?

Into adulthood.

Filopodia

Long, fingerlike extensions from growth cones of axons and dendrites.

What was found in the first studies of sensory deprivation vs. enriched environments as it pertains to neurodevelopment?

Looking at animals reared in the dark, rats from birth in the dark were found to have fewer synapses and fewer dendritic spines in their primary visual cortexes, and as adults were found to have deficits in depth and pattern vision. The first studies of early exposure to enriched environments found that enrichment had beneficial effects. Rats raised in such environments had thicker cortexes with more dendritic spines and. more synapses per neuron. Early studies of sensory restriction in rats has been extended to human studies of babies with cataracts in both eyes, rendering them blind. They found that when the cataracts were removed between 1-9 months after birth, their vision was comparable to that of a newborn. Some aspects of their vision improved quickly but some deficits were still present 2 years later.

Cell-Adhesion Molecules (CAMs)

Molecules on the surface of cells that have the ability to recognize specific molecules on the surface of other cells and adhere to them.

Radical Migration

Movement of cells in the developing neural tube from the ventricular zone in a straight line outward toward the tube's outer wall.

Tangential Migration

Movement of cells in the developing neural tube in a direction parallel, at a right angle, to the tube's walls.

Adult _______________ occurs in at least two areas of the human brain.

Neurogenesis

Where do the neurons created during adult neurogenesis come from?

New olfactory bulb and stratal neurons are created from adult neural stem cells at certain sites in the sub ventricular zone of the lateral ventricles and then migrate to the olfactory bulbs or striatum. New hippocampal cells are created near their final location in the dentate gyrus of the hippocampus.

The competitive nature of neurodevelopment has been demonstrated by the effects of early monocular deprivation on the size of _______________.

Ocular dominance columns.

Glia-Mediated Migration

One of two major modes of neural migration during development, by which immature neurons move out from the central canal along radial glial cells.

Somal Translocation

One of two major modes of neural migration, in which an extension grows out from the undeveloped neuron and draws the cell body up into it. It seems to explore the immediate environment for attractive and repulsive cues as it grows.

Inside-Out Pattern

Orderly waves of migrating cells, processing from deeper to more superficial layers. Each wave of cortical cells migrate through the already formed lower layers of cortex before reaching its destination.

Instructive Experiences

Particular experiences that contribute to the information in genetic programs and influence the course of development. A type of experience on brain development.

Necrosis

Passive cell death. Necrotic cells break apart and spill their contents into extracellular fluid, and the consequence is a potentially harmful inflammation.

What are popular theories about adult hippocampal neurogenesis?

Pattern separation - the new hippocampal neurons in memory function, including forgetting, with the ability to separate distinct precepts into individual memories for storage. Another theory says that neurogenesis serves a role in mood and anxiety regulation. Finally, physical activity promoting neurogenesis, with those who are more active having greater amounts of neurogenesis, which assists with the adaptation to complex environments.

Gap Junctions

Points of communication between adjacent cells, which are bridged by narrow tubes called connexions through which cells can exchange cytoplasm. They play a role in migration and aggression and other prevalent aspects of neurodevelopment.

The last part of the human brain to reach maturity is the _______________ cortex.

Prefrontal

_______________ is the tendency to continue making a formerly correct response when it is currently incorrect.

Preservation

What does reduced cortical development in the parietal and occipital lobes, and in the oribitofrontal cortex may be related to regarding Williams Syndrome?

Profound impairment of spatial cognition and remarkable hyper sociability.

Guidance Molecules

Released by glial cells; attract or repel axons. Chemicals which guide various classes of migrating neurons by either attracting or repelling them. They play an important role in neurodevelopment because the brain can't function unless each class of developing neurons reaches the right location.

Retinal Ganglion Cells

Retinal neurons whose axons leave the eyeball and from the optic nerve. They can regenerate.

What do neural tube deficits cause?

Severe birth defects of the CNS and can result from errors in the folding process from the neural groove.

What are the phenotypic characteristics of people with Williams Syndrome?

Short stature, small upturned noses, oval ears, broad mouths, full lips, puffy eyes, and small chins.

The development of the human brain is unique in one respect: The human brain develops far more _______________ than the brains of other species.

Slowly

What are the two methods by which cells migrate in the developing neural tube?

Somal Translocation and Glia-Mediated Migration

The postnatal growth of the human brain results from myelination, dendritic branching, and _______________.

Synaptogenesis.

What did they find about adult rats and neurogenesis?

That adult rats living in enriched environments produced 60% more new hippocampal neurons than rats in non enriched environments. However, it depends on the amount of exercise that typically occurs in that environment. This suggests that since the hippocampus is involved in some kinds of memory, exercise may reduce or delay memory problems.

What is the most recent discovery about synaptogenesis?

That it depends on the presence of glial cells, particularly astrocytes.

What have studies shown about early music training?

That it influences the organization of the human cortex - it expands the area of auditory cortex that response to complex musical tones.

Pattern Separation

The ability to separate distinct percepts into individual memories for storage.

Aggregation

The alignment of neurons during the development of the nervous system. Once developing neurons have migrated, they MUST align themselves with other developing neurons that have migrated to the same area to form structures of the system.

What has research on the neural mechanisms of ASD focused on?

The atypical reaction of individuals with ASD to faces: they spend less time than typical looking at faces, particularly at the eyes, and they remember faces less well. The Fusiform Face Area in ASD individuals was found to display less fMRI activity than typical in response to presentation of faces.

Where is cortical thinning the greatest in Williams Syndrome?

The boundary of the parietal and occipital lobes, and in the oribitofrontal cortex.

Orbitofrontal Cortex

The cortex of the inferior frontal lobes, adjacent to the orbits, which receives olfactory input from the thalamus.

What is the first major stage of neurodevelopment in all vertebrates?

The development of the neural plate.

Pioneer Growth Cones

The first growth cones to travel along a particular route in the developing nervous system. Presumed to follow the correct trail by interacting with guidance molecules along the same route. Subsequent cones follow the same routes with this tendency to follow along the path established by preceding axons called fasciculation.

Nerve Growth Factor (NGF)

The first neurotrophin to be discovered.

Synaptogenesis

The formation of new synapses.

Neurogenesis

The growth of new neurons.

Topographic Gradient Hypothesis

The hypothesis that axonal growth is guided by the relative position of the cell bodies on intersecting gradients, rather than by point-to-point coding of neural connections. Proposed to explain accurate axonal growth involving topographic mapping of the developing brain. Axons growing from one topographic surfaces (ex retina) to another (ex optic tectum) are guided to specific targets that are arranged on the terminal surface in the same way as the axons' cell bodies are arranged on the original surface. Growing axons are guided to their destinations by two intersecting signal gradients (ex anterior-posterior gradient and a medial-lateral gradient). Spontaneous neural activity and neuron-astrocyte interactions have also been shown to contribute to topographic mapping.

Chemoaffinity Hypothesis

The hypothesis that growing axons are attracted to the correct targets by different chemicals released by the target sites. Proposed by Sperry. Theory of axonal development. Proposes that each postsynaptic surface in the nervous system releases a specific chemical label and that each growing axon is attracted by the label to its postsynaptic target during both neural development and regeneration. Many guidance molecules for axon growth have been identified. But the hypothesis failed to account for the discord that some growing axons follow the same circuitous route to reach their target in every member of a species rather than growing directly to it. A revised hypothesis states that the growing axon isn't attracted to its target but growth cones are influenced by a series of chemical and physical signals along the route which the axonal guideposts being similar to those that guide neural migration. Some guide, some repel, with other signals coming from adjacent growing axons.

Superior Temporal Gyrus

The large gyrus of the temporal lobe adjacent to the lateral fissure; the location of the auditory cortex. Includes primary and secondary cortex.

Optic Tectum

The main destination of retinal ganglion cells in non-mammalian vertebrates. Called the superior colliculus in mammals.

Mesoderm Layer

The middle of the three cell layers in the developing embryo. The area is referred to as an organizer.

ASD Savants

The most single remarkable aspect of ASD is the tendency for some people with ASSD to savants - people with developmental disabilities who nevertheless display amazing and specific cognitive or artistic abilities. Between 10-30% display these abilities. About 50% of savants are diagnosed with ASD with abilities taking forms such as feats of memory, naming days of the week for ANY future or past dates, identifying prime numbers, drawing, musical instruments, etc. These abilities don't appear to develop through learning or practice and emerge spontaneously. Can emerge in otherwise healthy people following brain damage or transcranial magnetic stimulation to the left anterior temporal lobe. Investigators speculated that somehow atypical development of certain parts of their brains has led to compensatory responses in other parts.

Migration

The movement of cells from their site of creation in the ventricular zone of the neural tube to their appropriate target location.

What does the growing neural plate form?

The neural groove.

What do the lips of the neural groove fuse to form?

The neural tube

What area of the human brain has the most prolonged period of development?

The prefrontal cortex.

Connexins

The proteins that make up gap junctions.

Neural Proliferation

The rapid increase in the number of neurons that follows the formation of the neural tube. When the lips of the neural groove have fused to create the neural tube, its cells proliferate (increase in number) but not all simultaneously or equally.

Ventricular Zone

The region adjacent to the ventricle in the developing neural tube. The ventricle is the fluid filled centre of the neural tube.

What area of the brain is thicker in people with Williams Syndrome and what might it be related to?

The superior temporal gyrus. It may e related to the relatively high levels of language and music processing in those with the syndrome.

Fasciculation

The tendency of developing axons to grow along the paths established by preceding axons.

Preservation

The tendency to continue to make a formerly correct response that in currently incorrect. Children between 7-12 months tend to make this error - found in Piaget's studies. Hypothesized to occur because the neural circuitry of the prefrontal cortex is not yet developed during this period of a child's life. Synapse numbers in the prefrontal cortex aren't maximal until the 2nd year, and the correct performance of the task involved two of the major functions of that brain area: holding information in working memory and suppressing previously correct, BUT currently incorrect, responses.

Neural Tube

The tube that is formed in the vertebrate embryo when the edges of the neural groove fuse and that develops into the central nervous system. Inside the tube eventually becomes the cerebral ventricles and spinal cord. By 40 days after conception, 3 swellings are visible at the anterior end of the human neural tube which develop into the forebrain, midbrain and hindbrain.

What does the myelination of various areas of the human brain during development roughly parallel?

Their functional development.

During the period of cellular migration what are the cells lacking?

They are still in an immature form, lacking the processes (axons and dendrites) that characterize mature neurons.

What are the functions of neurons that are the products of adult neurogenesis?

Those that are generated in adulthood survive and become integrated into neural circuits and conduct neural signals. Adult generated olfactory bulb and stratal neurons become interneurons, and generated hippocampal neurons become granule cells in the dentate gyrus.

What does the postnatal growth of the human brain seem to result from?

Three kinds of growth: Synaptogenesis, myelination of axons and increased branching of dendrites.

What two major factors govern the migration in the developing neural tube?

Time and location.

Many studies have shown that early experience influences the _______________ maps of sensory cortex.

Topographic

What happens if you deprive one eye of vision for a few days early in life, but does not happen if both eyes are deprived?

When only one eye is blindfolded, the ability of that eye to activate the visual cortex is reduced, but the ability of the other eye increases. Both of these effects occur because early monocular deprivation changes the patter of synaptic input into layer IV of the primary visual cortex. Because ocular dominance columns in the IV layer of the primary visual cortex are largely developed at birth, blindfolding one eye for several days during the first few months of life reorganizes the system, with the widths of the columns of input from the deprived eye decreasing and the width of the non deprived eye increasing. This is a sensitive period which is specific to a species, with modest effects occurring into adulthood. Even a few days of monocular deprivation can produce a massive decrease in axonal branching of the lateral geniculate nucleus neurons that normally carry signals from the deprived eye to layer IV of the primary visual cortex.

Human cortical _______________ matter grows slowly and steadily until early adulthood.

White