240926 Lecture #8 - Early Brain Development.pdf

Brain Development: The Early Years… Department of Psychology and Neuroscience, Sept 26th, 2024 On August 6, 1945, the United States, in an attempt to quickly end the war in the pacific against Japan dropped the first of two atomic bombs, on the city of Hiroshima.  The Explosion...

Brain Development: The Early Years… Department of Psychology and Neuroscience, Sept 26th, 2024 On August 6, 1945, the United States, in an attempt to quickly end the war in the pacific against Japan dropped the first of two atomic bombs, on the city of Hiroshima.  The Explosion The 16 kiloton blast created a huge >37,000 °F fireball, generated >1,000 kmph winds and spread radioactivity (from 64kg of uranium-235) over a wide area… Before After  The Aftermath Hiroshima aftermath Injured civilian casualties (90,000–146,000 killed)  Figure 1. The proportion of severely mentally retarded cases and 90% confidence limits by DS86 uterine absorbed dose and postovulatory age in weeks. (Otake e t al. 1987.)  Figure 5. The proportion of small head cases and 95% confidence limits by DS86 uterine absorbed dose and trimester of pregnancy. (Otake and Schull 1993.)  Figure 4. The proportion of seizure cases and 95% confidence limits by DS86 uterine absorbed dose and postovulatory age. (Dunn e t al. 1990.) What We Know About Brain Development Brains are built over time, shaped by the interaction between genetics and experience. Social, emotional, and cognitive development are highly interrelated. Brain architecture and skills are built in a hierarchical “bottom-up” sequence. Brain plasticity and the ability to change behavior decrease over time.  brain development nutrition developmental behavioral & molecular genetics Psychobiological development Psychobehavioral development emotions memory cognition language attachment The Foundation of a Successful Society is Built in Early Childhood Three Core Concepts of Development  Central Nervous System (3 weeks – 20 years) During critical developmental processes, i.e., windows of susceptibility  Development of the Brain: overview Growth and Differentiation of the Vertebrate Brain Early Beginnings CNS begins to form at three weeks gestation Development of the neural tube At birth, brain weighs 350g, at one year 1,000g Growth and Development of Neurons Proliferation-production of new cells Migration-move toward final destination Differentiation-form axons and dendrites Myelination-addition of insulating sheath  Stages of Development Phase Approximate Age Highlight Prenatal Conception - birth Rapid physical growth Infancy Birth - 2 yrs Motor development Childhood 2 - 12 yrs Abstract reasoning Adolescence 13 - 25 yrs Identity creation, “Judgement” Directly related to maturation of the “Prefrontal Cortex”  Piaget’s Object Permanence Task 1896-1980 An infant sees a toy and then an investigator places a barrier in front of the toy. Infants younger than about 9 months old fail to reach for the hidden toy. Tasks that require a response to a stimulus that is no longer present depend on the prefrontal cortex, a structure that is slow to mature.  Phases of Prenatal Development Ovum + sperm – zygote Once zygote implants in uterus – embryo (composed of germinal layers of cells from which the various organs later derive) Week 8 until birth – fetus Prenatal Brain Development is primarily structural The nervous system begins to develop just before the third week of gestation. Cell creation and movement to the correct places occurs during the first five prenatal months.  5 Phases of brain development 1. Neural plate induction 2. Neural proliferation 3. Migration & Aggregation 4. Axon growth & Synapse formation 5. Cell death & Synapse rearrangement The Brain: embryonic development The University of South Wales, Dr. Mark Hill  The Brain: embryonic development The embryonic stage of development includes the process of organogenesis - transformation from the embryo to a body structure including defined organs. During the third week, the development of the primitive streak provides an axis upon which other structures can organize.  The Brain: embryonic development The process of neurulation in embryos generates a dorsal rod shaped structure termed a notochord (generated from the primitive streak) which serves as a primitive skeleton, later replaced by the vertebral column. The nervous system develops from the ectoderm located above the notochord. Nervous system development proceeds from the generation of the neural plate to neural folds, which eventually develop into the neural tube.  1. Induction of the Neural Plate 18 days after conception the embryo begins to implant in the uterine wall A patch of tissue on the dorsal surface of the embryo that will become the nervous system a. Consists of 3 germinal layers of cells: endoderm, mesoderm, and ectoderm. Thickening of the ectoderm germ layer leads to the development of the neural plate. b. The neural groove begins to develop at 20 days.  1. Induction of the Neural Plate 18 days after conception the embryo begins to implant in the uterine wall A patch of tissue on the dorsal surface of the embryo that will become the nervous system c. At 22 days the neural groove closes along the length of the embryo making the neural tube. d. A few days later brain subdivides into the: 1. Forebrain (telencephalon, diencephalon) 2. Midbrain (mesencephalon 3. Hindbrain (rhombencephalon). Neural Tube formation  5 Phases of brain development 1. Neural plate induction 2. Neural proliferation 3. Migration & Aggregation 4. Axon growth & Synapse formation 5. Cell death & Synapse rearrangement 2. Mitosis/Proliferation Neuroepithelial cells are the stem cells of the nervous system Neuroepithelial cells of the ectoderm proliferate –> generation of new cells 3 swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain Occurs in ventricular zone Rate can be 250,000/min After mitosis “daughter” cells become “fixed” post mitotic  5 Phases of brain development 1. Neural plate induction 2. Neural proliferation 3. Migration & Aggregation 4. Axon growth & Synapse formation 5. Cell death & Synapse rearrangement 3. Migration: slow movement to the right place Migrating neurons are immature, lacking dendrites, with only a soma and immature axon at this point Undifferentiated at start of migration. But, differentiation begins as neurons migrate. They develop neurotransmitter making ability, action potential  3. Migration: slow movement to the right place Neuroepithelial cells (neural stem cells) of the ventricular zone, give rise to radial glial cells that further differentiate into neurons or glial cells (e.g., astrocytes). Radial glial cells act as guide wires for the migration of neurons Migrating neurons are immature, with only a soma and immature axon Cells that are done migrating align themselves with others cells and form structures (Aggregation) http://www.nature.com/neuro/journal/v4/n2/extref/nn020 1-143-S1.mpg  The Brain: embryonic development 3-4 Weeks Brain develops from neural tube Brain subdivides into – Forebrain – Midbrain – Hindbrain These further divide, each with a fluid filled region: ventricle, aqueduct or canal – Spinal cord also has a canal Two major bends, or flexures, occur (midbrain and cervical) The Brain: embryonic development 5 to 6 Weeks The Brain: embryonic development Forebrain 5 to 6 Weeks Midbrain Hindbrain The Brain: embryonic development Photographs of Human Fetal Brain Development Lateral view of the human brain shown at one-third size at several stages of fetal development. Note the gradual emergence of Gyri and Sulci: Gyri (plural of gyrus) Elevated ridges Entire surface Grooves separate gyri A sulcus is a shallow groove (plural, sulci) Deeper grooves are fissures  Space restrictions force cerebral hemispheres to grow posteriorly over rest of brain, enveloping it Cerebral hemispheres grow into horseshoe shape (b and c) Continued growth causes creases, folds and wrinkles The CNS has two kinds of tissue: Gray and White Matter Gray matter – neuronal cell bodies (brown when fixed), dendrites and axon terminals of neurons, so it is where all synapses are. White matter – neuronal axons coated with electrical insulation called myelin, connecting different parts of grey matter to each other  5 Phases of brain development 1. Neural plate induction 2. Neural proliferation 3. Migration & Aggregation 4. Axon growth & Synapse formation 5. Cell death & Synapse rearrangement  4. Axon Growth/Synaptogenesis Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow to their “mature” size/shape. Axons (with growth cones on end) and dendrites form a synapse with other neurons or tissue (e.g., muscle) Growth cones and chemo-attractants are critical for this (e.g., NGF). http://www.youtube.com/watch?v=Fgmt2RBow0I  4. Axon Growth/Synaptogenesis 2 types of cells: – Neurons – Glial cells (~10:1) Formation of new synapses is termed synaptogenesis Although most neurons are formed halfway through gestation there are virtually no synaptic connections – it is experience and interaction with the environment that forms the synaptic connections Most synaptogenesis occurs through the 2nd year of life 83% of dendritic growth (connections between synapses) occurs after birth  Synapses are essential to neuronal function Synaptic Cleft – space between neurons at Neuron cell a nerve synapse across which a nerve impulse is transmitted by a neurotransmitter Nucleus Dendrite Soma Axon Myelin sheath Node of Ranvier Schwann cell Axon terminal Sources: http://main.zerotothree.org/site/PageServer?pagename=t er_key_brainFAQ Dendrites – receives messages from other cells Diagram: http://en.wikipedia.org/wiki/Human_brain_cell Axon terminal – passes on messages to other cells Brain Cells develop connections over the first 2 years Then they are sculpted actively for ~20 yrs  Although most of the brain material and size is in place at the start of adolescence, several important developmental processes continue…e.g., myelination & synaptic refinement/rearrangement Rate of Changeà Source: Tapert & Schweinsburg, 2005  5 Phases of brain development 1. Neural plate induction 2. Neural proliferation 3. Migration & Aggregation 4. Axon growth & Synapse formation 5. Cell death & Synapse rearrangement  5. Neuronal Death After birth - development is refinement of neuronal connections, maturity of the neurons, and increasing complexity of dendrite interconnections. Between 40-75% neurons made, will die after migration – death is normal and necessary !! Neurons die due to failure to compete for chemicals provided by targets Neurotrophins - a family of proteins (e.g., NGF, BDNF): – promote growth and survival – guide axons – stimulate synaptogenesis Axons not exposed to neurotropins after making connections undergo apoptosis, a preprogrammed mechanism of cell death. – therefore, the healthy adult nervous system contains no neurons that failed to make appropriate connections. Use it or lose it – Natural Selection of Brain Wiring (Neural Darwinism) Neurons and synapses must get hooked together properly to develop specific skills and abilities in humans How the “right” connections are made is still being researched During infancy and early childhood the developing cortex overproduces synapses (2X as needed) The overproduction leads to a competition for survival of the fittest synapses (competition for neurotrophin, nerve growth factor) After maturity, the apoptotic mechanisms become dormant. Neurons no longer need neurotrophins for survivals, but neurotrophins increase the branching on axons and dendrites throughout life.  Synaptogenesis & Pruning In cortex, synapses begin to form after neuronal migration, 23 weeks prenatal However, most synapses form after birth Many form randomly (as axons and dendrites meet) Flourish, then selectively prune Up to 100,000 synapses pruned per second (Kolb, 1999) Birth 6 yrs old 14 yrs old  Synaptic production and pruning correspond with overall brain activity Young children’s brains work harder and less efficiently than adults’  Two Types of Synapse Development 1. Experience-expectant development – Overproduce synapses, prune with experience – “Experience leads to less” – Tied to critical/sensitive periods – Organizes brain to process information, behaviors expected for all humans Sensory processes Parental attachment Eye-hand coordination Language capacity Greenough & Black, 1999  Two Types of Synapse Development 2. Experience- dependent development – New synapses formed, maybe some pruning – “Experience leads to more” – Continues throughout life – Codes experiences/learning that is person-specific A particular language Specific knowledge, memories, skills Greenough & Black, 1999  Lesson from Rat Experiments Standard housing More Complex (Enriched) housing Infant Rats: Adult Rats – Enrichment REDUCED – Enrichment INCREASED synapse density synapse density – Facilitated pruning of – Facilitated growth of new excess synapses in experience-expectant synapses in experience- development dependent development – Prune>Gain – Gain>Prune Experience influences both pruning and growth of new synapses in an age dependent manner (Kolb, Gibb, Dallison, 1999). Rearrangement of synapses during development Active synapses — receive enough neurotrophic factor to remain stable Inactive synapses — receive too little neurotrophic factor to remain stable Release and uptake Neurons receiving Axonal processes of neurotrophic insufficient complete for limited factors neurotropic factor die neurotrophic factor  Synaptic Re-arrangement, cont’d: Myelination Time after synaptogenesis The process whereby glial cells (formed by oligodendrocytes in the CNS and Schwann cells in PNS) wrap themselves around axons Increase speed of action potential conduction down the axon Begins at birth, rapidly increases to 2-years old Continues to increase more slowly through 30-years-old Synaptic Re-arrangement, cont’d: Myelination In adults dendritic growth and synapse refinement are coated with myelin which serves as an electrical insulation When electrical impulses travel from neuron to neuron, some of their “strength” can be lost or “leaked” or can collide and interfere with other impulses Myelination speeds up the travel of the impulses and makes their travel more efficient Myelin is composed of 15 % cholesterol with 20 % protein which is why doctors recommend breast milk for babies—myelin content and speeds of electrical signals Deoni et al., NeuroImage 2013. 82:15; pp 77–86 rise with breastfeeding. Summary of the Eight Phases in Embryonic and Fetal Development at a Cellular Level 1. Mitosis/ 2. Migration 3. Differentiation 5. Synaptogenesis Proliferation 4. Aggregation 6. Neuron Death 7. Synapse Re- 8. Myelination arrangement  Postnatal Cerebral Development in Human Infants Postnatal growth is a consequence of – Synaptogenesis – Increased dendritic branches – Myelination (prefrontal cortex continues into adolescence) Overproduction of synapses may underlie the greater “plasticity” of the young brain Young brain more able to recover function after injury, as compared to older brain  The brain has a left hemisphere and a right hemisphere covered by a layer of nerve tissue called the cerebrum (cerebral cortex). Each half of the cerebrum has four different lobes. Underneath the cerebrum are other brain structures, including the amygdala, thalamus, corpus callosum, and hippocampus, all of which play important roles in human behavior, memory and emotions.  Brain Structures and Their Functions The brain is made of three main parts: 1. Forebrain -> cerebrum (cortex), thalamus, and hypothalamus (part of the limbic system) 2. Midbrain -> tectum and tegmentum. 3. Hindbrain -> cerebellum, pons and medulla. Often the midbrain, pons, and medulla are referred to together as the brainstem. The cerebrum or cortex is divided into four lobes: Self-regulation, Sensory motor perception, Hearing, language, problem solving, goal Vision and perception spatial abilities memory, social - setting, social emotional function cognition  Brain Stem (“survival”) Basic functions including heart rate, breathing, sleeping, eating. Limbic System (“emotion”) Cerebellum (“movement”) The Cerebrum or Cortex is Divided into Four Lobes  Occipital Lobe (visual input) Processes visual input that is sent to the brain from the retinas  Temporal Lobe (auditory input) Combines auditory and visual information, as well as recognition depending on memory (i.e., faces, music). Hearing Languag e Memory Emotion  Parietal Lobe (general sensory input) The major sensory inputs from the skin (touch, temperature, and pain receptors) relay through the thalamus to parietal lobe. Frontal Lobe (general intellect and motor control) Judgment Emotional regulation Problem solving Decisions Planning Creativity  The Frontal Lobes “Executive Functions” Governing emotions Judgment Planning Organization Problem Solving Impulse Inhibition Abstraction Analysis/synthesis Self-awareness* Self-concept* Identity *Self- “everything” Spirituality Williamsgroup, 2003: Please credit Protecting You/Protecting Me (PY/PM) Implications of Arrested Development: Adolescent Behaviour Maturation Occurs from Back to Front of the Brain Images of Brain Development in Healthy Youth (Ages 5 – 20) Blue represents maturing of brain areas Earlier development of the back of the brain and later development of the front of the brain … Preference for physical activity Less than optimal planning and judgment More risky, impulsive behaviours Copyright © 2004 The National Academy of Sciences, USA Gogtay, N., Giedd, J.N., et al. (2004) Minimal consideration of Dynamic mapping of human cortical development during childhood through early adulthood Proceedings of the National Academy of Sciences, 101 (21), 8174 – 8179 negative consequences Source: Gogtay, Giedd, et al., 2004. Implications of Arrested Development: Adolescent Behaviour Maturation Occurs from Back to Front of the Brain Images of Brain Development in Healthy Youth (Ages 5 – 20) Blue represents maturing of brain areas Earlier development of the back of the brain and later development of the front of the brain … Preference for physical activity Less than optimal planning and judgment More risky, impulsive behaviours Minimal consideration of negative consequences Kirill Oreshkin Mapping of Cortical Thinning with Longitudinal MRI Data Gogtay et al., PNAS, 2004 The Frontal Lobe is Very Sensitive to early Experience Frontal lobe development is a long process beginning prenatally and continuing until early adulthood. It is altered by a wide range of positive and negative experiences. e.g., parent-infant interactions; drugs; stress  Neuroplasticity in Adults Mature brain changes and adapts Neurogenesis (birth of new neurons) – seen only in olfactory bulb and hippocampus of adult mammals – Not clear if this is critical for “normal” adult behavior Potential mechanisms underlying the requirement of neurogenesis in mediating antidepressant responses (Annales Pharmaceutiques Françaises (2013) 71, 143-149)