Week 4 (Axonal Pathfinding/Survival)

Adult Neurogenesis

  • Previously thought to be impossible

    • thought we are born with all the neurons we will ever have

  • Some regions of the brain can regenerate some neurons

    • Neurons in the dentate gyrus of the hippocampus in humans and other mammals

    • Neurons in the subventricular zone (SVZ) of the lateral ventricles

Axonal Pathfinding

  • During development the brain needs to send neurons axons to specific targets in the brain

    • This process is called axonal pathfinding

  • Axon connections are specific

    • Sensory and motor axons find their way to their targets

  • The tip of the axon is called a growth cone

    • end feet are called filopodia

    • They can sense molecules around them which can guide them to their targets

Sperry Experiments

  • Frogs can regenerate nerves after being cut

  • If you rotate the eye of the frog and cut the optic nerve, it will regrow the axons to the original synaptic sites

  • We learned that axons will find their way to their correct target even if we alter the eye and severe connections

  • There is a hypothesis that involved chemical gradients

Chemical Gradient Hypothesis

  • Growing axons follow cell surface molecules

    • These molecules are attracted to and repelled by other chemicals

    • Axons then follow gradients of chemicals

  • Axons with the highest concentration of a chemical or protein navigate to brain areas with highest concentration of this chemical/protein

    • Axons with lowest concentration go to regions with lowest concentration of the chemical/protein

Axonal Competition

  • Axons synapses onto multiple cells in the approximate location of their target

  • This ensures that at least one of the synapses will reach the proper target

  • The proper synapse will be strengthen

  • All the other unnecessary synapses then will die

Neuronal Survival

  • How is it that each muscle and gland is innervated by the exact amount of axons needed?

    • Each 50% more neurons are produced than required, so they cannot all stay

  • In the peripheral nervous system muscles help determine how many axons survive

    • Muscles that receive a synapse with an axon deliver a protein called nerve growth factor (NGF)

    • This is a nuerotrophin that promotes the growth and survival for the axon

    • Axons that do not receive NGF die

  • In the CNS is currently unknown

    • In general the easiest way to ensure survival is to be useful

    • Continue having synaptic transmission between 2 or more neurons

Neuron Death

  • Two separate processes of neuron death

  • Necrosis

    • Passive cell death

    • Necrosis is more dangerous, as parts of the cell can spill into extracellular fluid causing inflammation

  • Apoptosis

    • Active cell death

    • Apoptosis is safer, it bundles pieces to be recycled

    • If the process is blocked it could cause cancer

    • If inappropriately activated it could result in a neurodegenerative disease

  • Neuron death is a sign of maturation

  • System becomes more efficient