Wiring the Brain

Wiring the Brain

1. Wiring Diagram models

   • Pruned
     • No specificity for neuropil outgrowth
     • Final connections emerge through loss of functionally inappropriate connections
   • Set
     • Specific to start with, and occurs via two ways
       • "I know where to go"
       • With guides

2. Growth cone

   • Flat sheets of membrane = Lamellipodia
   • Thin spikes moving in and out = filopodia
     • Growth occurs when filopodium takes hold of substrate and pulls growth cone forward
   • Substrate
     • Fibrous proteins
     • Permissive substrate
       • Laminin (glycoprotein)
         • Is bound by integrin on axon surface
           • Promotes axon elongation
       • Bordered by repulsive substrates
         • = corridor channeling axon growth along specific pathway
     • GAP-43 (Growth-associated protein)
       • In high concentration in growing axons
   • Fasciculation
     • Growing axons stick together
       • Cell-adhesion molecules (CAMs)

3. Extracellular Matrix

   • Composition
     • Glycosaminoglycans (mucopolysaccharides)
     • Fibrous proteins with growth factors and proteases
     • Proteoglycans
       • Chondroitin Sulfate (CSPGs)
         • Lecticans
           • Aggrecan
           • Versican
           • Neurocan
           • Brevican
         • Matrix-associated proteoglycans
           • Phosphacan
         • Cell-surface proteoglycans
           • Neuroglycan C
       • Keratyn Sulfate (KSPGs)
       • Heparan Sulfate (HSPGs)
       • Tenascin
         • Cross-links CSPGs and binds them using CSPG side chains
     • Others
       • Hyaluronan
       • Collagens
       • Elastins
       • Fibronectins
       • Laminins
       • CAMs (Cell-adhesion molecules)
         • Immunoglobins
         • Integrins
         • Selectins
         • Cadherins
   • Components
     • Interstitial matrix
     • Basement membrane
       • Basal Lamina
         • Lamina Lucida
         • Lamina Densa
       • Reticular Lamina

4. How axons move

   • Axons move through EM using connections between integrins and laminin, fibronectin and collagen
     • Indirect connections: via alpha actinin + proteins
   • NCAMS (neural cell-adhesion molecules)
     • Fasciculation (bundling of axons)
     • NGF (Neural growth factor)
       • Promotes undirected neural growth