Neurodevelopmental Disorders PDF

Neurodevelopmental Disorders Dr. Caroline Witton Neurodevelopment By the end of this part of the lecture you should be able to: ‒ Describe the main stages of neurodevelopment, and know their timecourses Formation of the Neural Tube (“Stage 0”) 1 Neural Proliferatio...

Neurodevelopmental Disorders Dr. Caroline Witton Neurodevelopment By the end of this part of the lecture you should be able to: ‒ Describe the main stages of neurodevelopment, and know their timecourses Formation of the Neural Tube (“Stage 0”) 1 Neural Proliferation 2 Neural Migration 3 Neural Differentiation 4 Synaptogenesis 5 Apoptosis 6 Synaptic reorganisation Some facts: The adult brain comprises ~80 billion neurons (15 times more than the number of humans on Earth) During early embryonic life, neurons are added at a rate of 250,000 neurons /min Almost all structure of brain present at birth Growth @ 2 years after birth ~80% of adult size A single neuron interacts with an average of 15,000 other cells Rapid physical changes (see the YouTube video) Gastrulation During the first 2 weeks of embryonic life Formation of the neural tube, 2-4 weeks 2 weeks 3 weeks 4 weeks Neurulation The neural tube forms the basis of the brain and spinal cord The basis of the spinal ganglia of the autonomic nervous system emerge now The rostral (front) part of the neural tube develops 3 chambers which eventually become the ventricles https://ehp.niehs.nih.gov/doi/full/10.1289/ EHP2268 Stages of Neurodevelopment 1-3 Neurogenesis Neural migration Neural differentiation Neurogenesis Progenitor (stem) cells divide in the neural tube by mitosis. Early in development they divide symmetrically, to increase number s of progenitor cells Later they split asymmetrically into one progenitor cell and one immature neuron (or glial cell). Peak: 8-16 weeks after conception  Neural migration Newly-formed neurons in the ventricular zone are guided into position by radial glia cells Each successive wave of neurons passes neurons that migrated earlier, so the most recently formed Cross-section through cortex during development neurons occupy layers closer to the cortical Traffic windows: 8-16wks surface. (heavy); then slowed until 25wks Neural differentiation When the immature neurons are in position, they differentiate into different types of specialised neurons … resulting in the laminar structure of cortex I. Molecular layer II. External granular layer III. External pyramidal layer IV. Internal granular layer V. Internal pyramidal layer VI. Fusiform layer  Time-course of Neurodevelopment Prenatal Postnatal Conception Birth 4 8 12 16 20 24 28 32 ¼ 2 5 18 60+ weeks years Neurogenesis Max growth Neurulation Synaptogenesis Competitive elimination Migration from ventricular zone Programmed Apoptosis Myelination Dendritic and axonal arborisation The brain continues to grow after birth Stages 4-6 Synaptogenesis Apoptosis Synapse reorganisation Synaptogenesis Over-production of synapses, redundancy Begins from about 17 weeks after conception but is mostly postnatal Apoptosis (cell death) Clearing of neurons whose axons don’t find their targets Activated by genetic processes inside a cell, different from necrosis From as early as 16 weeks after conception until after birth Synaptic reorganisation At birth 6 years old 14 years old From about 26 weeks after conception until after birth Myelination Myelin is produced by oligodendrocytes, a type of glial cell Gradual increase in the myelin sheath surrounding the axons ‒ Starts in the visual system before birth then progresses to other sensory systems ‒ Sensory pathways myelinated before motor ones; ‒ All white matter fibre tracts have myelination before 2 years From about 28 weeks after conception until after birth  Time-course of Neurodevelopment Prenatal Postnatal Conception Birth 4 8 12 16 20 24 28 32 ¼ 2 5 18 60+ weeks years Neurogenesis Max growth Neurulation Synaptogenesis Competitive elimination Migration from ventricular zone Programmed Apoptosis Myelination Dendritic and axonal arborisation https://www.nature.com/news/neurodevelopment-unlocking-the-brain-1.10925