Todays session, “Synaptic Receptor and Regulation” has been a wonderful overview of a great diversity of synaptic components. Across the talks, it is abundantly clear that synaptic proteins – particularly those located in the post-synaptic density (PSD) are over-represented in mental and developmental disorders. Hence, it is clear that understanding how these proteins work will help understand brain-related illness. Another common theme is that most of the proteins discussed so far seem to interact via a common latticework of proteins such as PSD95 and gephrin which are prone to polymerize in ways that provide a scaffold for ion channels and other receptors that intitiate action potentials. Hence, it seems that 3-D structure IS function when talking about synapses. Just a smattering of highlights for me were:
-amazing 3-D tomographic reconstructions of the PSD
-protein palmitoylation is necessary for proper spine formation (perhaps because ras & rho use such modifications during signalling?)
-that a conformational change in collybistin upon binding with neuroligins is what promotes the clustering of ion channels
-a failure to stabilize AMPA receptors is an underlying cause of mental retardation
-the localization of synapses in the axon initial segment is regulated by neurofascin – which is expressed just there in that very tiny aspect of a neuron!
-beautiful 3-D reconstructions of dentrites, spines and astrocytes entwined together and also detailed freeze-fracture replica images of AMPA receptor localization (clustered in the center of the active zone) and NMDA channels (more diffusely spaced)
-the dishevelled gene (the mouse knockout has a behavioral phenotype) regulates AcH receptor localization in c. elegans.
-red hot chilli pepper spice (a.k.a. capsaicin) is actually able to cause AMPA receptors to internalize and depress neural activity.
-the PSD is highly conserved in vertebrates and has very ancient evolutionary roots as far back as our common ancestor with yeast! yet the most divergent genes are those involved in neural development.
-still trying to figure out what “the calyx of held” is … more on that later … blasted wifi here
Genes 2 Brains 2 Mind 2 Me 
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