How Does the Nervous System Develop and Adapt PDF

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This lecture discusses the neurobiology of development, correlating behavior with nervous system development, and brain development and the environment....

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How Does the Nervous System Develop and Adapt? Chapter 8

Neurobiology of development 

Embryonic vertebrate nervous system o Forebrain, midbrain, and hindbrain are visible in the human embryo at about 28 days

Gross Development of the Human Nervous System  Prenatal Stages o Zygote: Fertilization to 2 weeks o Embryo: 2 to 8 weeks o Fetus: 9 weeks to birth  Neural Plate (3 weeks after conception): Thickened region of the ectodermal layer that gives rise to the neural tube  Neural Tube: Structure in the early stage of brain development from which the brain and spinal cord develop  Major Events o Day 49: Embryo begins to resemble a miniature person o Day 60: Sexual differentiation; genitals and brain regions o Day 100: Brain looks distinctly human o 7 months: Gyri and sulci begin to form o 9 months: Brain looks like an adult brain Origins of Neurons and Glia  Neural Stem Cell: A self-renewing multipotential cell that gives rise to neurons and glia o Line the neural tube and have an extensive capacity for self-renewal o When stem cell divides, it produces two stem cells  One dies and the other lives to divide again o This process repeats again and again throughout a person’s lifetime  Subventricular zone: Lining of neural stem cells surrounding the ventricles in adults  Progenitor Cell: Precursor cell derived from a stem cell o Progenitor cell migrates and produces a neuron or glial cell o Produces non-dividing cells known as neuroblasts and glioblasts  Neuroblast: gives rise to different types of neurons  Glioblast: gives rise to different types of glial cells  How do stem cells know what to become? o Chemical signal  Turns genes on (gene expression)  Specific proteins are made o Specific cells o Different genes are activated by different chemical environments  Produces different proteins and different cell types o Epigenetics: Methylation alters gene expression dramatically during development o Neurotropic Factor: A chemical compound that acts to support growth and differention in developing neurons  May help keep certain neurons alive in adulthood  Epidermal Growth Fact (EGF)  Stem cell  Progenitor cell

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Basic Fibroblast Growth Factor (bFGF)  Progenitor cell  Neuroblast

Growth and Development of Neurons  Stages of Brain Development o Cell Birth (neurogenesis; gliogenesis)  A chemical compounds act to support growth and differentiation in developing neurons; begins about 7 weeks after conception  Largely complete by 5 months  Exception: Hippocampus makes new cells throughout life  Brain can more easily cope with injury during this time (first 5 months of gestation) o Cell migration  Begins shortly after first neurons are generated  Continues for 6 weeks in cortex and longer in hippocampus  Damage has more serious consequences  Radial Glial Cell: Path-making cell that a migrating neuron follows to its appropriate destination o Cell Diffusion  Neuroblasts become specific types of neurons  Begins after cells have begun to migrate  Essentially complete at birth  Although neuron maturation, which includes the growth of dendrites, axons, and synapses, goes on for years and, in some parts of the brain, may continue throughout adulthood o Cell Maturation (dendrite and axon growth)  Ventricular zone contains a primitive map of the cortex that predisposes cells to migrate to certain locations  Cells migrate to inner layers first, and then to outer layers (layers 6, 5, 4, 3, 2, and 1)  Differentiation is dependent upon genetic instructions, timing, and signals from other cells in the local environment  Neural Maturation  After neurons migrate to their final destinations and differentiate into specific neuron types  Mature in two ways: o Dendritic growth: grow dendrites to provide surface area for synapses with other cells  Arborization (branching_  Growth of dendritic spines where most synapses occur  Slower (micrometers/day) than axonal growth (millimeters/day) o Axonal Growth: extend their axons to appropriate targets to initiate synapse formation  Growth cone: Growing tip of an axon  Filopod: Process at the end of an developing axon that reaches out to search for a potential target or to sample the intercellular environment  Cell-adhesion molecule (CAM)  On the target cell’s surface or in intercellular space  Provide surface for growth cones to adhere  Serve to attract or repel growth cones  Tropic molecule  Produced by targets being sought by the axons  Tell growth cones to “come over here”  Likely they tell other growth cones seeking different targets to “keep away”

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Synaptogenesis (formation of synapses)  Synaptic Development  10^14 synapses in the adult human cerebral cortex  Combination of genetic programming and environmental cues and signals  5th gestational month: simple synaptic contacts  7th gestational month: synaptic development of deep cortical neurons  After birth: synaptic development increases rapidly during the first year of life. Cell Death and Synaptic Pruning  The brain “chisels” away “pieces” by using cell death and synaptic pruning  Chisels: genetic signal, experience, reproductive hormones, and even stress  Cortex becomes measurably thinner in a caudal-rostral (back-to-front) gradient, a process that is probably due largely to synaptic pruning  We are born with an overabundance of neurons and synaptic connections  Neural Darwinism: Hypothesis that cell death and synaptic pruning are, like natural selection in species, the outcome of competition among neurons for connections and metabolic resources in a neural environment  Apoptosis: Genetically programmed cell death  Synaptic connections that are not part of a functional network are pruned away in an experience-dependent manner  Unique Aspects of Frontal-Lobe Development  Frontal lobe is the last brain region to mature  Maturation extends far beyond age 20 o The frontal lobe is especially sensitive to epigenetics influences o The trajectory of frontal lobe development correlates with adult intelligence Myelogenesis (formation of myelin)  Glial Development  Birth of astrocytes and oligodendrocytes begins after most neurogenesis is complete and continues throughout life  Oligodendria form myelin in CNS  Myelination provides a useful rough index of cerebral maturation

Correlating Behavior with Nervous System development 

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Three Approaches for studying the correlation between Brain and behavior development o Structural development can be studied and correlated with the emergence of behavior o Behavioral development can be analyzed, and predictions made about what underlying circuitry must be emerging o Factors that influence both brain structure and behavioral development can be studied  For example: hormones, genes, experience, injury Behaviors cannot emerge until the requisite neural machinery has developed When that machinery is in place, related behaviors develop quickly through stages and are shaped significantly by epigenetic factors

Motor Behaviors  2 months: axons from motor-cortex are myelinated at about the time that reaching and grasping develop  4 months: group of motor-cortex neurons known to control finger movements are myelinated at about the time pincer grasp develops  10 months: increased motor dexterity is associated with a decrease in cortical thickness in the hand region of the left motor cortex of right handers. Language Development  Language onset is usually between 1 and 2 years of age

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Language acquisition is largely complete by age 12 Neural changes during this time: o Increased dendritic complexity and interconnections o Increased myelination in speech areas

Correlations between Gray-Matter Thickness and Behavior  Red dots corresponds to regions showing significant cortical thinning correlated with improved motor skills  White dots correspond to regions showing significant cortical thickening correlated with improved language skills  Red dots show regions of decreased cortical thickness correlated with improved vocabulary scores Development of Problem-Solving Ability (Jean Piaget, 1952)  Birth to 18-24 months o Stage I: sensorimotor  Experiences the world through senses and actions (looking, touching, mouthing) o Object permanence; stranger anxiety  About 2-6 years o Stage II: Preoperational  Represents things with words and images but lacks logical reasoning o Pretend play; egocentrism; language development  About 7-11 years o Stage III: Concrete operational  Thinks logically about concrete events; grasps concrete analogies and performs arithmetical operations o Conservation; mathematical transformations  About 12+ years o Stage IV: Formal operational  Reasons abstractly o Abstract logic; potential for mature moral reasoning  Growth spurts o Sporadic period of sudden growth that lasts for a finite time o Epstein (1979)  Identified five spurts in brain growth during development  First four coincide with onset of Piaget’s stages, and the last occurs around 14 to 16 years  Likely due to growth of glial cells, blood vessels, myelin, and synapses Caution: Correlation does not equal Causation  Remember: Just because two tings correlate (take place together) does not mean that one of them causes the other

Brain development and the environment   

Brains exposed to different environmental experiences are molded in different ways Culture is an important aspect of the human environment, so culture must help to mold the human brain People raised in widely different cultures may acquire differences in brain structure that have lifelong effects on their behavior

Experience and cortical organization  Hebb (1947) o Cognitively stimulating environments help maximize intellectual development o Compared with rats raised in standard lab cages, those raised in “enriched environments” had:  Larger synapses and more synapses

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Larger astrocytes and more astrocytes

Experience and Neural Connectivity  Prenatally o Neurons or their axons and dendrites are drawn toward a signaling chemical that indicates the correct pathway (Sperry, 1963)  Postnatally o Fine-tuning of connections proceeds in an activity-dependent manner  But what happens if one of the eyes is prevented from receiving light stimulation? o Effects of preventing light stimulation to the right eye during a critical period of visual development  Evidence for postnatal fine tuning: Amblyopia o A condition in which vision in one eye is reduced as a result of disuse; usually caused by a failure of the two eyes to point in the same direction o Visual input from the “lazy eye” does not contribute to the fine tuning of neural connections Critical Periods for Experience and Brain Development  Critical Period o Developmental “window” during which some event has a long-lasting influence on the brain o Often referred to as a sensitive period o Example: Imprinting  Process that predisposes an animal to form an attachment to objects or other animals at a critical period in development  Typically, right or just after birth  In chicks: associated with enlargement of synapses in forebrain Abnormal Experience and Brain Development  Early deprivation of sensory experience o For example, being placed in the dark o Produces the opposite effect of cognitively stimulating environments: atrophy of dendrites  Early deprivation of social experience o For example, being raised without maternal contact o Produces a profoundly negative effect on later intellectual and social behaviors  Stress in early life has been associated with: o Increased size of amygdala o Decreased size of hippocampus o Later development of depression and anxiety disorders Hormones and Brain Development  Sex Hormones o Released during a brief period in the course of prenatal brain development and subsequently alters the brain much as it alters the sex organs o Androgrens (for example, testosterone): Sex hormones responsible for distinguishing characteristics of the male o Estrogens: sex hormones responsible for the distinguishing characteristics of the female  The presence of testosterone and estrogen both affect the development of the brain o No. of neurons formed o No. of neurons that die o Cell growth o Dendritic branching o Synaptic growth o Activity of synapses

Not just areas of brain related to sexual behavior: these hormones can affect development of “higher functions” such as cognition Bachevalier and colleagues: Postnatal Effects o Monkeys  Male and females show different patterns of performance on tests at 2.5 months old  Males that had testes removed at birth performed more like females o Humans  Similarly, males and females show different patterns of performance around 15 to 30 months of age  However, sew differences disappeared at 32 to 55 months of age Juraska (1990): Postnatal Effects o Rats Reared in Complex Environments  Males showed more dendritic growth in visual cortex than females  Females showed more dendritic growth in frontal lobes than males o Summary:  Sex differences in brain structure exist throughout development o

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Developmental Disability  Impaired cognitive functioning due to abnormal brain development o Many causes  Genetic abnormalities (e.g., Down syndrome)  Prenatal exposure to infections (e.g., rubella) or drugs/toxins such as alcohol (e.g., fetal alcohol syndrome)  Brith trauma, such as snoxia (e.g., cerebral palsy_  Malnutrition  Environmental abnormality, such as sensory deprivation (e.g., Romanian orphans)  Purpura (1974) o Examined the brains of children with developmental disabilities who died from accidents or diseases unrelated to the nervous system o Compared with normal children, dendritic growth was reduced in children with various forms of mental retardation  Suggests that there were fewer connections in the brain....