Neuroplasticity Development of the Nervous System

Between 4 weeks and 9 months the brain undergoes rapid development

Development of the Brain Stages of neuroanatomical development a. Zygote stage: Begins upon fertilization of the ovum i. 2 sets of 22 chromosomes, and one set of sex chromosomes. Total of 23 pairs of chromosomes (XX= female, XY= male)

ii. Stages of fertilization (1) hours – first cell division (2) 3 days – division continues until a solid ball is formed (3) 5 days – continue to divide, but cells move toward outer edge of blastocyst (4) 6 days – cells begin to move inward (5) 8 days – beginning of embryonic disc & zygote becomes attached to the uterus (6) 14 days – zygote is completely attached to the uterus and embryonic disc is fully formed

From Conception to 8 days

b. Embryonic stage (14 days – 8 weeks): Begins at the full formation of embryonic disc i. Mesoderm: contains chemical signals for various areas of nervous system; directs formation ii. Endoderm: forms everything else iii. Ectoderm: forms nervous system (brain), fingernails, hair, and skin. Changes: 1. Thickens in the middle (neural plate) 2. Groove starts to form (neural groove) 3. Groove closes to form tube (neural tube) a. At the top of canal is neural crest, forms PNS

Simplified View of Neural Plate Formation

Formation of the Neural Plate with the thickening of Ectoderm

Formation of the Brain, Spinal Cord and PNS (Neuroectoderm)

iv. Neuroectoderm forms when foundation for the three main structures has been developed: 1. 3 swellings a. Hindbrain b. Midbrain c. Forebrain 2. Closed Neural Tube becomes spinal cord central canal and ventricles of the brain v. Spina bifida – Neural Tube Defect (NTD) - spinal cord doesn’t close, often linked to mental retardation **NTDs can be discovered in utero **

vi. Amount of mesoderm in relation to ectoderm determines the nervous system region 1. Amount of signal/tissue coming from mesoderm determines spinal cord/brain Determination: A process that ensures that a population of cells will give rise to specific systems in developing organism Regional specificity: Once signal is in place we lose the plasticity of the blastocysts. Irreversible signal set by a genetic code after formation of neuroectoderm.

Ectoderm to Neuroectoderm: 20 days to 30 days

Fetal Period: Two Months to Birth (38 weeks)

Fetal Period Foundation for the entire CNS is set 6 stages of CNS development complete the prenatal process

Neuronal Proliferation (embryonic stage through fetal stage) Midbrain Ventricular Intermediate Marginal Hindbrain Zone Zone Zone Forebrain Ventricul. SubV Intermed. Cortical Marginal Zone Zone Zone Plate Zone

Neuronal Proliferation

Six Stages of Nervous System Development

1. Mitosis (cell division) or Neurogenesis in the ventricular zone, One cell division can lead to a daughter cell, will divide again forming an immature neuron 2. Migration: cells move from VZ to their destination; this migration is aided by glial cells, abnormal migration found in a number of disorders. Filopodia assist in finding location after leaving radial glial cells. Abnormalities in migration are present in people with learning disabilities, schizophrenia and autism (more on this in a little while)

Cell Migration During Brain Development: Hindbrain & Midbrain

Forebrain Development

Growth Cones & Filopodia

Filopodia

3. Differentiation: The Process which gives rise to specific neurons and glial cells 4. Synaptogenesis: Neuronal maturation 1. Elongation of axons (w/growth cones) 2. Establish terminals 3. Elongation of dendrites 4. Expression of NT Neurotrophic factors – stimulate cell growth, i.e. nerve growth, factor helps neuron to mature.

5. Normal cell death (more on this later) - Apotosis – active cell death during development - Necrosis – passive cell death due to injury 6. Synaptic rearrangement: dependent on apotosis and experience!!!!

Theories as to why/how this happens 1. Chemoaffinity hypothesis – Post synaptic cell is releasing a chemical 2. Blueprint hypothesis – Cell adhesion molecule present, guides neuron to destination 3. Topographic gradient hypothesis – Axons are growing based on position of cell body, spatial growth **All three appear correct, happens differently in different areas**

Postnatal Development of the Central Nervous System

Post-natal brain development 1. At birth the brain weighs 25% of the full adult brain 2. By the age of 6 it increases to 95% i. Increase is due to myelination a. At birth the brain is myelinated through the thalamus b. Myelination is in part based on experience (the premature baby will have substantially more myelin than that of the full term baby)

ii. Proliferation of glial cells iii. Last wave of neurogenesis iv. Maturation of neurons v. Increase in synaptic connectivity

Cellular Development of the Postnatal Brain Cells of the Cerebral Cortex

Cell of the Cerebellum

Brain Development Occurs in Waves through Age 21 Temporal Parietal Limbic Frontal

Brain Increases Connections Between Birth and 21 years old. Age

Changes from Birth – 21: Temporal Lobes or Language Areas Age

Changes from Birth – 21: Parietal-Temporal Areas for Higher Cognitive Functioning Age

Changes from Birth – 21: Limbic System for Emotions/Attachment Age

Changes from Birth – 21: Frontal Lobes for Behavioral Control Age

VII. How experience affects development 1. Neural activity regulates gene expression that directs synthesis of cell adhesion molecules 2. Neuronal activity regulates the release of neurotrophins (NGF) that are released from the dendrites; after synaptic connectivity 3. Stimulates foundation NT and this promotes subsequent development

Experience can Modify Brain Cell Connections

Active Cell Death – 40% occurs during the first 2 years of life, and it occurs on a different scale in adolescence (hormone related, final sculpting 1. Essential because many cells are unconnected and useless 2. Dysfunction in apoptosis is seen in post- mortem brains of children with autism (particularly problems in cerebellum, midbrain, & hippocampus); insufficient hooking up of neurons

Removal of Brain Cells during Early Childhood

Brain Cells can Continue to Develop in Abnormal Ways Early Childhood Adulthood

Example of normal and abnormal cell connections and arrangements that can occur in different brain systems.