Surprising Discoveries about Synapse Evolution with Seth Grant (BSP 51)

Episode 51 of the Brain Science Podcast is an interview with Dr. Seth Grant from Cambridge University, UK.  Dr. Grant's work focuses on the proteins that make up the receptors within synapses. (Synapses are the key structures by which neurons send and receive signals.) By comparing the proteins that are present in the synapses in different species Dr. Grant has come to some surprising conclusions about the evolution of the synapse and the evolution of the brain.

In this interview Dr. Grant explains how his research team has uncovered the identity of  synapse proteins in a variety of species including yeast, fruit flies, and mice. Our discussion is centered on the paper he published in Nature Neuroscience in June 2008. Dr. Grant's team has made several surprising discoveries. First, he has discovered that some proteins associated with neuron signaling are actually found in primitive unicellular organisms like yeast. He has also discovered that the protein structure of the synapse becomes more complex as one moves from invertebrates like fruit flies to vertebrates like mice, but that most of the complexity seems to have arisen early on in vertebrates.

According to Dr. Grant:

The origins of the brain appear to be in a protosynapse or ancient set of proteins found in unicellular animals, and when unicellular animals evolved into metazoans or multicellular animals their protosynaptic architecture was coopted and embelished by the addition of new proteins onto that ancient protosynaptic set, and that set of new molecules was inserted into the junctions of the first neurons or the synapse between the first neurons in simple invertebrate animals. When invertebrates evolved into vertebrates, around a billion years ago, there was a further addition or enhancement of the number of these synaptic molecules and that has been conserved throughout vertebrate evolution where they have much larger numbers of synaptic molecules. The large complex synapses evolved before large anatomically complex brains.

The discovery that there are significant differences between the synapses in vertebrates and non-vertebrates is significant because it has long been assumed that synapses were essentially identical between species and that brain and behavioral complexity was based on having more neurons and bigger brains. Instead, Dr. Grant proposes an alternative hypothesis:

The first part of the brain to ever evolve was the protosynapse. In other words, synapses came first.

When this big synapse evolved what the vertebrate brain then did as it grew bigger and evolved afterwards; it exploited the new proteins that had evolved into making new types of neurons in new types of regions of the brain. In other words, we would like to put forward the view that the synapse evolution has allowed brain specialization, regionalization, to occur.

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Addition Show Notes and Links:

References:

• "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes." Nature Neuroscience 2000 Jul;3(7):661-9. Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG.


• "Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases." Human Molecular Genetics 2005 Oct 15;14 Spec No. 2:R225-34. Grant SG, Marshall MC, Page KL, Cumiskey MA, Armstrong JD.


• “The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour.” Molecular Systems Biology 2: 2006.0023. Pocklington AJ, Cumiskey M, Armstrong JD, Grant SG.


• "Evolutionary expansion and anatomical specialization of synapse proteome complexity." Nature Neuroscience 2008. Emes RD, Pocklington AJ, Anderson CN, Bayes A, Collins MO, Vickers CA, Croning MD, Malik BR, Choudhary JS, Armstrong JD, Grant SG

Blog posts and other links:

• Press Release from Genes to Cognition on Brain Evolution.  June 2008


• New York Times article by Nicholas Wade (6/10/08)


• "Synapse Proteomics," by Diane Jacobs. June 2008


• "Synapse Proteomics & Brain Evolution." Neurophilosophy blog. June 2008


• "Increasing complexity of nerve synapses during evolution." Deric Bownds. June 2008

Learn more about Dr. Grant's work:

• Genes to Cognitions (G2C) website


• Dr. Grant's faculty page

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