NEURAL DEVELOPMENT - L4

NEURAL DEVELOPMENT - L4

1. SCULPTING THE DEVELOPING BRAIN

   • Genes interact with experience to guide brain development
     • -->genes-->behaviour-->environment
     • growth and development of the brain are orderly process
   • A ZYGOTE - fertilised egg - 46 chromosomes, within a week a human embyro will develop three cell layers
     • ECTODERM: the outer layer, becomes the nervous system
       • the NEURAL GROOVE forms between ridges of ectoderm
     • 18 days: endoderm, mesoderm, ectoderm, neural plate, notochord, primitive streak, notochord
     • 20 days: neural groove becomes the midline
       • the neural tube forms from the neural ridges
     • 22 days: interior tube becomes fluid-filled cerebral ventricles of the brain, the central canal of the spinal cord and the passages that connect them
     • 24 days: forebrain (prosencephalon) + telencephalon and diencephalon, mid brain, hind brain, dorsal root ganglion, neural tube, spinal cord
       • at 8th week, most organs have formed, gradual emergence of gyri and sulci
   • the anterior part of the neural tube has three subdivisions - forebrain, midbrain and hindbrain

2. THE SIX STAGES OF NEURAL DEVELOPMENT

   • 1. Neurogenesis – mitosis produces neurons from non-neuronal cells. The production of nerve cells. Cells of the neural tube diVide through mitosis and form the ventricular zone
     • ADULT NEUROGENESIS:
       • At birth mammals will already produce most of the neurons they will have
       • Postnatal increase of brain weight is due to growth in the size of neurons, dendrites branching, myelination, increases glial cells
       • However, a tiny percentage of neurons are acquired in adulthood known as adult neurogenesis (hippocampus)
       • The rate of adult neurogenesis can be increased with enriched experiences such as learning and exercise
   • 2. CELL MIGRATION - cells move to establish distinct populations
     • The cells produced migrate to their appropriate regions. Not random – radial glial cells act as guides for cells to migrate along. CELL ADHESION MOLECULES (CAMs) promote adhesion of parts of the nervous system to guide cells. Some cells remain in the ventricular zone to continue neurogenesis. Some cells migrate to the marginal zone
     • 3. DIFFERENTIATION - cells become distinctive neurons or glial cells
       • When cells reach their destinations, they begin to express genes to make the proteins they need. Allows a cell to acquire its specific appearance and function of a neuron in that region
       • TWO TYPES OF INFLUENCES ON DIFFERENTIATION. (1) Cell-autonomous (self-organisation) – independent of other cells and driven by genes, intrinsic organisation as seen in vitro (in cell culture). (2) Induction (neural environment) – cells are affected by the influence of other neighbouring cells
       • Cells differentiate into the appropriate cell type for their location. Regulation is the response to cell injury in development; other cells will develop and take its place. Stem cells are undifferentiated cells that can divide, and their daughter cells can assume a new cell fate
       • 4. SYNAPTOGENESIS - establishment of synapatic connection
         • Neurons extend their axons and dendrites and form many synapses with one another. Process outgrowth – growth of axons and dendrite. Extensions emerge from growth comes at the tips of axons and dendrites. Filopodia are the fine outgrowths of growth cones - adhere to CAMs in the environment and pull the growth cone in a particular direction.
           • Synaptogenesis – proliferation of synapses - Synapses form rapidly on dendrites and dendritic spines - Spines proliferate after birth, and connections are affected by experience - The nerve cell body increases in volume to support the metabolic needs of the dendritic tree
         • Axons are guided by chemicals released by the target cells - Chemoattractant are chemical signals that attract certain growth cones - Chemorepellents repel growth cones
         • 5. NEURONAL CELL DEATH - selective death of many nerve cells
           • Cell death, apoptosis, normal part of development. Not due to defect, choosing to die and actively committing suicide. Cells have death genes that are expressed only during apoptosis. Caspases are a family of proteases that cup up proteins and DNA
             • APOPTOSIS ---- Starts with a Ca2+ influx that causes mitochondria to release a protein, diablo. Diablo binds to inhibitors of apoptosis proteins (IAPs), which normally inhibit the caspases. Without IAP inhibition, the caspases are able to dismantle the cell
               • Several factors influence cell death in the nervous system --- If the size of synaptic target is reduced, fewer neurons survive. Neurons that make enough synapses survive and grow, those that fail die. Neurons also compete for chemicals the target cells make, called neutrophic factors and without enough, they die
                 • FORMING THE 6 CEREBRAL CORTEX LAYERS
                   • Cells of the cerebral cortex arrive in waves. Each successive wave forms a new outer layer.
                     • Eventually the six outer layers are formed with the latest arrivals on the outside
         • 6. SYNAPSE REARRANGEMENT - loss or development of synapses, to refine synaptic connections
           • Refine synaptic connections. One influence on synaptic survival is neural activity. Possibly, active synapses take up neurotrophic factor to maintain synapse. Inactive synapses receive too little neurotrophic factor to remain stable

3. NEURAL PLASTICITY

   • o The ability of the nervous system to change in response to experience or the environment. Brain is plastic when young - Injury to one part of the brain can allow function to develop in other brain areas. As we age plasticity slows down and becomes more static

4. PART 2

   • cannabis
     • Active substance is THC. THC targets THC receptors throughout the brain. Receptors are metabotropic and THC acts as an agonist for the THC receptor. Because lots of THC receptors are found in the hippocampus, memory loss is a serious side effect of marijuana use
     • AGONIST - – acts the same way as the neurotransmitter would act, antagonist = opposite. Agonists activates but doesn’t need it, so it gets killed off – not being required because too much is going on, so the receptors get removed for what it needs.
     • Antagonist – drug getting block, receptors can’t open, post synaptic neuron releases more receptors to get the signal in- more chance for it to function properly (up regulation). Counter-act effect of antagonist – body response to create more receptors, physically adapts to the drug, more antagonist to block receptors so more drug is needed, and this is how addiction occurs.
   • REVIEW - Electrical (action potential) – within neurons, transmission of signal along axon - Chemical (neurotransmission) – between neurons, transmission at the synapse - Electrical (EPSP & IPSP) – in the next neuron
     • 1. Different channels, action potential = K+ allow potassium in and out whenever you want. Open all the time potassium, sodium closed special stimulation needed, potassium channels that are open and closed for business. 2. Depolarising, starting to get positive, not enough stimulation for sodium channels to open yet, positive voltage is beginning to happen, everything warming up. Once It hits -40 is when explosion happens, calcium channels love threshold and open up – 3. voltage triggers them, sodium rushes in voltage jumps from -40 to 40, influx of sodium into the cell makes this happen 4. potassium is still closed but as it comes down it triggers the thing to open, cells are getting really positive
   • THE SEQUENCE OF TRANSMISSION
     • PRE-SYNAPTIC TERMINAL 1. Action potential travels down the axon to the axon terminal 2. Voltage-gated calcium channels open and calcium ions (Ca2+) enter pre-synaptic terminal 3. Calcium allows synaptic vesicles to fuse with membrane and release transmitter into the synaptic cleft: exocytosis
     • POST-SYNAPTIC TERMINAL 4. Transmitters cross the cleft and bind to postsynaptic receptors and cause EPSP or IPSP 5. EPSPs or IPSPs spread toward the postsynaptic axon hillock 6. Transmitter is inactivated (by enzymatic degradation) or removed (by transporters for reuptake and recycling) – action is brief
     • Putting it all together: motor reflex A neural chain is a simple series of neurons. The knee jerk reflex is a circuit for the stretch reflex, consisting of: - Sensory neuron - 2 synapses - Motor neuron
       • Neurons and synapses combine to make circuits The knee jerk reflex is extremely fast (~40ms): - Axons are myelinated and large - Sensory cells synapse directly onto motor neurons - Uses fast, ionotropic synapses