1. Neurodevelopment involves the formation of neurons, their selection and migration to the proper areas of the brain, and the growth of synapses between neurons. 2. In adulthood, neurogenesis continues in two small areas of the brain. Synapses can also be lost through stress, aging or disease but can be restored through learning, exercise, therapies and treatments. 3. During development, neurons are formed, selected and migrate to their proper locations. Defects can occur during these processes and lead to neurological or psychiatric conditions. Synaptogenesis and pruning further shape the brain through adolescence.

1. NEUROPLASTICITY AND
NEURODEGENERATION
Adapted from Steven Stahl, MD, PHD

2. Synaptic development and synaptic
neurotransmission.
• Neurodevelopment
• Neuronal selection
• Neuronal migration
• Synaptogenesis
• Competitive elimination

3. Time course of neurodevelopment

4. Overview of Neurodevelopment

5. Neurogenesis also occurs in adult life
• In adult life neurogenesis occurs in only two
areas of the brain:
• in the dentate nucleus of the hyppocampus
and in the olfactory bulb.

6. Adult Neurogenesis in the
hippocampus

7. Synapse loss and restoration
• Stress, aging and neurodegeneration can
cause loss of the synapse with or without
neuronal loss.
• Learning, exercise, growth factors,
antidepressants and psychotherapy cause
restoration of the synapse and of neurons.
• Transplantation of stem cells is another way to
restore the neurons or the synapses.

8. Growth Factors (promote neuronal
restoration)

9. Necrosis vs. Apoptosis
• In necrosis neurons are being destroyed by
suffocation or toxins/poisons(neuronal
assassination).
• In apoptosis neurons are being destroyed by
the activation of a gene inside the cell’s
DNA(neuronal suicide).

10. Neuronal death
(necrosis vs. apoptosis)

11. Neurodevelopment
• During neurodevelopment, neurons are
formed in excess (some are normal and some
are defective) then they are selected for
performing their duties.
• The defective neurons are eliminated.
• In developmental disorders the defective
neurons may be selected leading to a
neurologic or psychiatric condition.

12. Neuronal Selection during
neurodevelopment

13. Neuronal Migration
• After neurons are selected, they must migrate to
the right parts of the brain.
• In order to migrate, neurons trace either glial
cells or the neurons that already migrated.
• Migration is helped by adhesion molecules on the
neuronal surfaces and complementary molecules
on the glia.
• If migration is successful, the neurons are
properly aligned to grow, develop and form
synapses.

14. Good migration vs. defective migration

15. Proper migration requires recognition
and adhesion molecules

16. Synaptogenesis
• Synaptogenesis is directed by neurotrophins.
• Neurotrophins are molecules that cause neurons
to sprout an axonal growth cone.
• Once the growth cone is formed the neurons and
glia in the area make recognition molecules that
can be ATTRACTIVE or REPULSIVE.
• Repulsive neurotrophins cause the neurons to
grow away from them, while attractive
neurotrophins cause the neurons to grow
towards them.

17. Attractive and Repulsive neurotrophins

18. Axonal growth cone “docking”

19. Dendritic growth
• Just like the axons, dendritic growth is
controlled by growth factors that promote
branching of the dendritic tree.

20. Insufficient dendritic arborization
leads to defective synaptogenesis.

21. Formation of a Synapse
• Presynaptic axons contain some of the
molecular components necessary to form a
synaptic connection even before making
contact with a postsynaptic site.
• A synapse is formed in stages:

22. Stage 1 - Hemisynapse

23. Stage 2(obtaining supplies)

24. Stage 3 (extracellular scaffolding)

25. Stage 4 (intracellular scaffolding)

26. Stage 5 (adding elements)

27. Long term potentiation
Frequent utilization of synapse leads to:
• increased flexibility of the postsynaptic site,
• Increased neurotransmitter release
• postsynaptic receptors increase in number
• surface area of the postsynaptic neuron
increases
• adjacent postsynaptic sites form

28. Utilization of a synapse increases its
flexibility

29. Released neurotransmitters
strengthen the synapse

30. Adjacent synapses form in the
presynaptic and postsynaptic neurons

31. Dendritic pruning
The dendritic tree is constantly changing
throughout life, it can:
• sprout new branches, grow and establish
synaptic connections when necessary
• trims, alter or destroy synaptic connections
when necessary (pruning)

32. Normal pruning

33. Abnormal pruning(in degenerative
diseases)

34. Out of control neurotransmission
• Can increase the intracellular calcium which
• can lead to dendritic death and
• even cell death.

35. Abnormal dendritic pruning due to
increased neurotransmission

36. Competitive Elimination
• Between birth and age 6 synapses are formed
at an accelerated rate
• During adolescence competitive elimination
(pruning) occurs destroying about 50% of the
synapses.

37. Competitive Elimination of synapses in
adolescence