Development of Nervous System

Development of Nervous System

1. Matching of axons and target cells

   • Particular classes of neurons express molecules that recognise
     • Particular axon paths
     • Molecules in target cells
   • Molecules specific to class of neurons e.g. motorneurons - not to individual neurons
   • Presence of gradients of molecules organise the orderly arrangement of synapses
   • Conclusion from this is that the pattern of connections between retina and tectum and movement information represented is not based on experience

2. Presence of target tissue

   • Neuromuscular junction - each comoponent began development separately

3. Topographic maps

   • Many axonal projections within the nervous system establish an orderly arrangement of connections within their target field
   • Maps are arranged that the cells of origin is reflected in order of axon terminations
   • Neighbouring cells have axon terminal fields in neighbouring parts of target area

4. Visual system

   • Axons of retinal ganglion cells project along the optic nerve to lateral geniculate nucleus
   • Some axons project to both sides of brain
   • Cells in lateral geniculate nucleus, then project axons to specific regions of visual cortex
   • Both LGN receive inputs from two eyes and visual cortex then receives axons and carry responses from two eyes

5. Determines the ordered projection

   • When retinal axons from different retinal halves or quadrants deflected from normal position
   • Normal visual system
     • Nasal retinal cells form synapses with posterior tectum
     • Temporal retina form synapses with anterior tectum
   • Axons from temporal retina, avoid contact with posterior tectal cells
   • Thought that target region, molecules are expressed that provide information about position
   • Axons growing into brain recognise them
   • Gradients of molecules in two directions
     • Anterior-posterior direction
     • Dorso-ventral axes of tectum

6. The Synapse

   • Specialised axon of contact that forms between axon and its target
   • Formation of synapses is called synaptogenesis
   • Synapse contains signalling molecules such as neurotransmitter and neuropeptides
   • Best studied system of synaptogenesis is arrival of motor neuron of striated muscle fibres, the neuromuscular junction
   • Many of principles of synapse formation in PNS can be applied to CNS synapse

7. Types of synapses

   • Electrical synapses
     • Occur at specialized sites, gap junction
     • Common in non-neural cells and early embryonic stages
   • Chemical synapses
     • Predominates in mature human nerous system
   • Axodendritic
     • Between axon terminals of one neuron and dendrites of another
     • Most common type of synapse
   • Axosomatic
     • Between axons and neuronal cell bodies
   • Axoaxonic, dendrodendritic and dendrosomatic
     • Less common types of synapses
     • Function not as well understood

8. Electrical Synapse

   • Gap Junction: adjacent cells electrically coupled through a channel
   • Ionic current, no neurotransmitters, cytoplasm continous, no synaptic cleft, brief delay, bidirectional
   • Chemical synapses
     • Presynaptic element: synaptic vesicles, active zone
     • Synaptic cleft, postsynaptic density

9. Synaptogenesis

   • Formation of selective connection between the developing axon and its target
   • Differentiation of the axonal growth cone into a nerve terminal
   • Development of post synaptic apparatus in target cell
   • Two cells exchange a variety of signals
     • Vesicles cluster at pre-synaptic site
     • Transmitter receptor cluster the post-synapic sites
   • Synaptic cleft forms
     • When growth cone contacts the target cell, a cleft forms
     • Multiple growth cones get attracted to the cleft
     • Myelin sheath forms around the synaptic cleft and synaptic connection is made

10. Neuromuscular junction

    • Synapse formation initiated when motor axon reaches a developing skeletal muscle and approaches immature muscle fibre
    • Presence of laminin inhibits motor axon growth and promote the accumulation of synaptic vesicles
    • After physical contact, the growth con transforms into nerve terminal and start to release ACh
    • As the muscle matures, multiple axons coverage on a single site
    • Axons but one are eliminated and both pre and post synaptic cell undergoe synaptic differentation including the formation of synaptic cleft
    • Three cell types
      • Motor neuron nerve terminal
      • Muscle fibre
      • Schwaan cells
      • Pre-terminal Schwann cells form myelin sheet
      • Muscle fibre forms junctional folds, rich in ACh-receptors
      • Basal lamina ensheaths the muscle, the synaptic portion rich in acetylcholin esterase which hydrolyses released ACh and terminates transmitter action
    • Nerve ad muscle organize each other's differentiation
    • Synaptic cleft contains adhesion molecules as laminin and collagen
    • Most synaptic components of motor neuron and myotube develop on their own

11. Motor nerve organizes differentiation of postsyaptic muscle membrane

    • Agrin is a large extracellular matrix proteoglycan
    • Activates membrane-associated receptor tryosine kinase triggering a casacde of intracellular reactions that results in clustering of AChRs
    • Neuregulin: Synthesized by both neuron and muscle, Activates erbB kinases in muscle, stimulates ACh receptor synthesis

12. Neuromuscular junction elimination

    • Adult mammals, there is one to one relationship between motor nerve terminals and muscle fibres
    • In embryo, several axons converge on each myotube and form synapses
    • Synapse elimination is not due to cell death but withdrawal of axonal branches
    • Neuronal activity supress AChR synthesis is non-synaptic areas
    • Synapse elimination occurs post natal

13. Synaptic input influence properties of post synaptic cell

    • Fast (Phasic) and slow motor neurons)
    • Effects of innervation by fast and slow nerves on muscles are mediated by their distinct pattern of activation

14. Central nerve terminals

    • Central synapses develop in a similar way to neuromuscular junction
    • Major protein components of synaptic vesicles similar to neuromuscular junction
    • Mechanism of transmitter release differ only quantitatively not qualitatevely
    • Synaptic elimination similar to that of neuromuscular junctions

15. Activity Dependent Tuning

    • Initial wiring is only approximate and leaes each neuronal axon connected to several places in neighbourhood of each of its targets
    • Activity dependent, mechanism is required to complete the development process
    • Initial chemical wriign actually produces more connections and somewhat more neurons that present adult brains

16. Postnatal development human infants

    • Parental growth is consequence of synaptogenesis, increased dendritic branches, myelination
    • Over production of synapses underlie greater plasticity of young brain

17. Synaptic Development

    • Experience-expectant development
      • Overproduce synapses, prune with experience

18. Functions of Synapse Elimination

    • Allows axons of different motor neurons to capture a number of cells appropriate to its size
    • Provides means by which normal function can change the strength of synaptic connections
    • Activity-driven neuronal connections are applicable to several situations during neuronal development and throughout life

19. Myelination

    • Begins near term
    • Continues throughout childhood and maybe the lifespan
    • Timing depends on area
    • Segmented structures composed of lipoprotein myelin
    • Form an insulating layer
    • Prevent leakage of electrical current
    • Increase speed of impulse conduction
    • Nodes of Ranvier - gaps along axon
      • Thick axons are myelinated
      • Axons are unmyelinated, conduct impulses more slowly

20. Myelination CNS

    • Oligodendrocytes forms the myelin sheaths in CNS
    • Multiple processes, coil around several different axons
    • Cranial-caudal temporal development in order of phylogenic development

21. Development of motor systems

    • New-born and reflexes
    • Babiniski's sign (Plantar Sole Reflex)
      • associated with upper motor neuron lesions anywhere along the corticospinal tract affecting lower extremeties

22. Convergence and Divergence

    • Rationale for starting with many is not as clear
    • Divergence also exists early in development 1 neuron
    • In muscle, the scenario of decreased convergence and divergence is recaptured when re-innervation occurs after injury

23. Effects of experience of development

    • Post natal development of nervous system results from interactions between neurons and their enviornment
    • Neurons and synapses that are activated by experience do not usually survive

24. Cell death during normal development

    • Cels die during the shaping of organs and at different stages of differentiation of organs
    • Characteristics: large numbers of neurons lost, reproducibly in same location, same time in species-specific manner

25. Determinants of cell survival or cell death

    • Factors shown to influence the amount of cell death or alter neuronal survival include
      • Amounts of target tissue
      • Factors from target or surrounding cells
    • Synaptic activity
    • Synaptic hormonal influences affect certain neuronal populations

26. Cell death can influenced by amount of target dervied factors

    • Target cells produce limited amount factors taken up by nerve terminals
    • Neurons that acceess those factors, survive
    • Thus increasing target size increased the amount of factor and number of cell deaths

27. Synaptic activity

    • Motor neurons innervating limb muscles - if neurotransmission between axons and muscles are blocked
    • Axons are electrically stimulate to increase synaptic activity
    • Anencephaly
      • Failure of anterior neurotubule to close
      • Brain is absent and replaced by tangle of glial and connective tissue

28. Nerve growth factor hypothesis

    • Sarcoma was secreting substance was taken up by nerve terminals and transported retrograde to cell body allow its survival

29. NGF transported retrogradely

    • Embyronic sensory neuron is culture. Culture dishes have a barrier to create two compartments but substances cannot diffuse between them
    • NGF - placed in different compartments and cell survival, neurite outgrowth assess for
    • Spinal cord syndrone (diplomyelia)
      • Splititing of notochord around an adhesion between endoderm and ectoderm
      • Causes formation of two neural tubes and two hemicords
      • Disorders of prosencephalic development
        • Prosencepalic formaiton - aprosencephaly/atelencephaly
        • Prosencephalic cleavage - holoprosencephaly/holotelnecephaly
    • Myeloschisis and Craniorachischisis
      • Plate-like mass of neurons tissue with no overlying skin or membrane
      • Neural folds fail to meet and fuse

30. Receptors for NGF

    • Two classes of NGF receptors
    • Irk receptor - a transmembrane protein containing a cytoplasmic tyrosin

31. Trophic interactions

    • Neurons depend on interactions to thrive
    • Regulates growth, diferentiation, survival, size of neuronal population innervating target

32. Neurolation - failure of neural tube closure

    • Ends by creation of neural tube which will give rise to CNS and neural crest at junction of neural tube and epidermis
    • Meningocele and myelomeningocele
      • Primary failure of neural tube closure - causing a spina bifidia
      • Asociated with folate deficiency