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.
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).
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.
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.
Proper migration requires recognition and adhesion molecules
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.
Dendritic growth• Just like the axons, dendritic growth is controlled by growth factors that promote branching of the dendritic tree.
Insufficient dendritic arborizationleads to defective synaptogenesis.
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:
Long term potentiationFrequent 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
Utilization of a synapse increases its flexibility
Released neurotransmitters strengthen the synapse
Adjacent synapses form in thepresynaptic and postsynaptic neurons
Dendritic pruningThe 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)