Home NEUR 310 Tuesday, January 21, 2014

Tuesday, January 21, 2014 CC-BY-NC
Neuron Target Interaction

Maintainer: admin

1Synapse

  • presynaptic active zone (electron dense)
  • synaptic cleft
    • PNS has clear synaptic basal lamina, CNS doesn't
    • has specialized extracellular matrix
  • postsynaptic membrane
    • has post-synaptic density (PSD)
    • anchor and cluster receptors and ion channels
  • CNS: both inhibitory (GABA) and excitatory (glutamate)
  • PNS: only exitatory

1.1synapse formation

  • two ways:

    • target selection : axon switch from a motile axon guidance mode to recognize target, activitiy-independent
      • ephrins repel axons of neurons expressing ephrin receptors
      • this allow topological mapping of retinal ganglion axons in tectum.
    • address selection: major remodeling of the initial course distribution, activity-dependent

  • motile growth cone touch the target and adhesion and differentiate

1.2PNS

  • NMJ : neuromuscular junction is often used to study synapses

    • ACh: transmitter at NMJ

  • maturation of NMJ

    • synapse formation involves dramatic clustering and concentrating of ACh Receptors
    • use bungarotoxin (BTX) to label AchR: shows that following innervation, receptors cluster and distribution maches presynaptic inputs
    • also switch from gamma to episolon subunit in AChR: change in eletrophysiological properties

  • 4 mecahnism of AChR clustering

    • redistribution of existing receptors
      • nerve directs the formation of cluster
      • Agrin : a heparin sulphate proteoglycan made by motoneurons
      • agrin binds to MuSK on post-synaptic terminal.
      • rapsyn links AChR to MuSK
    • increase stability on membrane
      • increase half-life
    • synaptic myonuclei upregualte AChR
      • neuregulin : secreted from presynaptic termianl
      • neuregulin -> erbB -> ras -> raf -> map -> > AchR gene
    • suppression of AChR gene transcription in non-synpatic nuclei

1.3CNS synapses

  • CNS neurons respond to more than one neurotransmitter, unlike NMJ in PNS

  • synCAM :

    • homophilic cell adhesion molecule on both sides of synapses
    • promotes excitatory glutamatergic synapse

  • Cadherins

    • homophilic transmembrane proteins, bind to each other
    • intracellular domains bind to b-catenin, which binds a-catenin, which binds actin
    • adhesive bridge
    • forms a donut shape at synaptic site, surrounding PSD95 complex

  • adaptors: Organizing receptor clusters

    • geophyrin: links glycine receptor (inhibitory) to microtubule
    • PSD95 complex, link NMDA-type glutamate receptor
    • proteins with PDZ domains : for proteiprotein interaction and linking

  • neurorexin-neuroligin

    • presynaptic beta-neurexin and post-synaptic neuroligin bind
    • link to intracelular adaptor proteins like PSD-95
    • like SynCAM, triggers presynaptic differentiation

  • active zone precursor vesicle

    • active and vesicles are arranged in precised grids, which determine how many vesicles are released
    • presyanptic active zone precursor vesicle: doesn't have synaptic vesicle proteins but help with increasing number of neurotransmitter relase

  • an incomplete model of CNS synapse formation

    • intial pre-post adhesion
    • recuritment of active zone precursor vesicles
    • recruitment of PSD scaffold proteins
    • recruitment of post-synaptic receptors by PSD scaffold proteins