Cognitive Science 320
Spring 2011

animated gifs
  • Drugs that affect presynaptic mechanisms
    • botulinum toxin (from the bacterium Clostridium botulinum, an anaerobic bacterium found in the soil): blocks docking by enzymatically cleaving synaptobrevin.
    • tetanus toxin (from the bacterium Clostridium tetani, an anaerobic bacterium found in the soil) blocks docking by enzymatically cleaving synaptobrevin.
    • a-latrotoxin (from black widow spider venom): causes massive release of neurotransmitter (affects neurexin)
    • hemicholinium: blocks the reuptake of choline into the presynaptic nerve terminal
synaptic vesicle proteins
synaptic vesicle life cycle
Figure 2.32 Gazzaniga et al

These images show some of the different molecules involved in (1) a vesicle attaching to the inside of the axon terminal's membrane and (2) release of the contents of the synaptic vesicle into the synaptic cleft (extracellular space).

NT = neurotransmitter

SB = synaptobrevin

SG = synaptogamin (synaptotagmin): may facilitate fusion of the membranes under the influence of Ca2+

ST = syntaxin

S25 = SNAP 25

 

In reality it is much more complex than shown above.  See the figure below copied from an article published May 2004 Nature Reviews Neuroscience

 

Molecular structure of CNS glutamatergic synapses

From the following article:

Cellular and molecular mechanisms of presynaptic assembly

Noam E. Ziv & Craig C. Garner
Nature Reviews Neuroscience 5, 385-399 (May 2004)
 doi:10.1038/nrn1370

 
     Current studies indicate that three distinct complexes help to define the active zone (see Table 1 for a list of key active zone proteins). The first complex is largely structural, and is thought to hold the active zone in register with the postsynaptic density (PSD) and clusters calcium channels within the active plasma membrane. It includes cell adhesion molecules (CAMs), including neuroligin, neurexin and N-cadherin, as well as synaptic CAM (SynCAM) and neuronal CAM (NCAM, not shown), and cytoskeletal proteins, such as piccolo, bassoon, ERC/Cast, liprin, calcium/calmodulin-dependent serine protein kinase (CASK), velis, mint and spectrin10, 12. The second complex is involved in synaptic vesicle docking and fusion, and it contains components of the SNARE complex, including syntaxin and Snap25, as well as Rim, Rab3a, Munc13, Munc18 and N and P/Q type calcium channels14, 15. Before fusion can occur, the synaptic vesicles must be primed, and molecules such as Rim, Munc13 and Munc18 are crucial for this step. Protein complexes that are involved in synaptic vesicle endocytosis include clathrin, dynamin and a family of SH3-domain-containing adaptor proteins26, 27.

Cellular and molecular mechanisms of presynaptic assembly 

Postsynaptically, PDZ-domain-containing proteins, such as SAP90/PSD95 (postsynaptic density protein 95), are abundant, and they are thought to build specialized protein complexes around specific subclasses of ionotropic glutamate receptors (NMDAR (N-methyl-D-aspartate), AMPAR (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor)) and metabotropic glutamate receptors (not shown)18, 19, 20. The tyrosine kinase receptor EphB is also tethered to the postsynaptic density, and it is an excellent candidate for regulating the recruitment of neurotransmitter receptors from endosomal pools. Proteins such as NARP and ephrin-B are thought to promote the clustering of AMPA and NMDA receptors, respectively10.

 

This picture of a serotonergic synapse shows autoreceptors presynaptically which are thought to be involved in regulating production of serotonin presynaptically.  "Serotonin levels in synapses are reduced by two kinds of synaptic molecules: autoreceptors (orange) which direct the cells to inhibit serotonin production, and reuptake transporters (yellow) which absorb the neurotransmitter."

Several antidepressants, including Prozac and Paxil, increase synaptic serotonin by inhibiting its reuptake." 

 

 

 

http://abdellab.sunderland.ac.uk/lectures/Parmacology/ANSdoc/serotonin3.html