Synapse stabilization

Synapse stabilization

1. Evolution of the brain / survival of the fittest connections

   • But synapses are refined throughout life
     • Are similar mechanisms involved in both development and memory?

2. Hebbian synapse

   • “Coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthen the synaptic connections between them.”

3. Synaptic refinement

   • Loss
     • Multiple examples – widespread phenomenon
       • Motorneuron axon / branch loss
         • Muscle fibres initially receive multiple inputs
           • In mature muscle, one input per muscle fibre
             • Every muscle fibre innervated
               • Non random - competition
       • Climbing fibre loss
         • Mature cerebelum – 1 CF per Purkinje cell
           • During development up to 4 CF’s per cell
   • Focusing
     • Climbing fibre re-organization
       • Initial contacts on soma
       • Mature contacts on dendrites
     • Ocular dominance columns
       • Mature inputs to layer IV are segregated
       • Immature inputs are not segregated
     • Connection focusing by competetion
       • Establishment of ODC’s is by competition
         • Monocular deprivation → spreading of non – deprived inputs
   • Transmitter choice
     • Choice of transmitter may depend on environment
       • Example: parasympathetic/ sympathetic neurons (MP)
         • Most SYMP are ADR+
         • Most PARA are ACh+
         • Transplantation
           • PARA → SYMP = ADR+
           • SYMP → PARA = ACh+
     • Changing transmitters
       • Target-dependent transmitter choice
         • Some symp neurons normally become ACh+
           • e.g. sweat glands / transplantation studies
   • Turning on synapses
     • Silent synapses in developing and mature systems
       • Intact, non-functional synapses
         • Activation like LTP in the mature hippocampus?
           • Transfection of GFP-labeled glutamate receptor subunits into hippocampal cells and slices
             • Appearance of GLUR1 at dendritic spines in LTP hippocampal slices
               • Strengthening of synapse
           • NMDA receptor involvement
             • APV blocks delivery of GLUR1
             • Recruitment of receptors occurs also in development
         • One mechanism for activating silent synapses may be “AMPAfication”
       • Seen in NMJ’s but focus on glutamatergic

4. Remember

   • Making synapses is a competition
   • Synapse formation / modification goes on throughout life
   • A successful synapse is a functional synapse
   • Use ‘em or lose ‘em