Seth Grant talks about Synapse Complexity (BS 176)

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BS 176 is my fifth interview with molecular biologist and neuroscientist Dr. Seth Grant from The University of Edinburgh. Dr. Grant was recently recognized for his pioneering work by the Federation of European Neuroscientists. He continues to make fundamental discoveries about the structure and function of the synapse and this month we discuss the discovery that synapse complexity and diversity is greater than expected, along with the  implications of these discoveries. 

Dr. Grant first appeared on Brain Science back in 2008. So in this interview, I also asked him to take us back through some of the key discoveries of his career. These include the discovery that the synapse is much more complex than previously assumed and the fact that this complexity preceded the evolution of animals with brains. More recently he has discovered that synapses are also more diverse than expected and that those in some parts of the brain are more complex than others.

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Links and References:

  • Seth Grant: University of Edinburgh

  • FENS EJN Award 2020

  • Cizeron M, Qiu Z, Koniaris B, et al. A brainwide atlas of synapses across the mouse life span. Science. 2020;369(6501):270-275. doi:10.1126/science.aba3163

  • Additional references are available in the episode transcript and in the show notes for previous episodes (Listed below)

Dr. Grant’s Previous Brain Science Interviews:

  • BSP 51: our first introduction to synapse complexity and evolution

  • BS 101: The role of the synapse in learning and disease

  • BS 137: How synapses change through out the lifespan

  • BS 150: Introducing the Synaptome and why it matters

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Explore the Synaptome with Seth Grant (BS 150)

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Explore the Synaptome with Seth Grant (BS 150)

BS 150 is our 4th interview of Seth Grant, the molecular biologist who has uncovered the fascinating evolution of synapse complexity. In this interview we learn about the first whole brain mapping of the mouse brain synaptome. We discuss the implications of the surprising level of diversity found in synapses in different brain areas. Dr Grant introduces us to a new theory of perception and memory recall.

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Seth Grant's latest Research (BS 137)

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Seth Grant's latest Research (BS 137)

In BS 137 neuroscientist Seth Grant introduces the "genetic lifespan calendar." He describes a new paper that describes how the genome determines the brain's complexity in "both time and space." This is the first paper to describe evidence that gene expression in the brain follows a predictable schedule that might offer new understanding of diseases like schizophrenia.

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Synapse Evolution with Seth Grant (BSP 101)

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Seth Grant (click photo to hear interview)

Seth Grant (click photo to hear interview)

Early in his career Seth Grant helped develop the transgenic mice that Eric Kandel used in his studies of how memory works. Since then he has combined his skill in genetics with his work on isolating the proteins that form the functional components of the synapse. (The synapse is a key component in the nervous systems of all multi-cellular animals.) When we last talked back in BSP 51 I was particularly struck by how many of these proteins actually evolved with single celled life--long before the arrival of nervous systems.

Recently Grant's work has focused on the discovery that the vertebrate synapse is actually much more complex than the one present in invertebrates. For BSP 101 we got together to talk about two papers he and his collegues recently published in Nature Neuroscience. These papers explore how small changes in the synapse proteins effect learning in measurable ways.

Grant has a special gift for making complex ideas clear, which means that this interview can be enjoyed by all listeners, even those who are new to the Brain Science Podcast and neuroscience. 

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References: 

  • S.G.N. Grant, T. J. O'Dell, K. A. Karl, P. L. Stein, P. Soriano, and E. R. Kandel, "Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice." Science 258 (1992):1903-10.

  • Emes RD, Pocklington AJ, Anderson CN, Bayes A, Collins MO, Vickers CA, Croning MD, Malik BR, Choudhary JS, Armstrong JD, Grant SG, "Evolutionary expansion and anatomical specialization of synapse proteome complexity." Nature Neuroscience 11 (2008) 799-806.

  • Nithianantharajah, J., Komiyama, N., McKechanie, A., Johnstone, M., Blackwood, D. H., Clair, D. S., Emes, R. D., van de Lagemaat, L. N., Saksida, L. M., Bussey, T. J. & Grant, S. G. N. “Synaptic scaffold evolution generated components of vertebrate cognitive complexity.” Nature Neuroscience 16 (2013) 16-24. doi:10.1038/nn.3276

  • Ryan, T. J., Kopanitsa, M. V., Indersmitten, T., Nithianantharajah, J., Afinowi, N. O., Pettit, C., Stanford, L. E., Sprengel, R., Saksida, L. M., Bussey, T. J., O'Dell, T. J., Grant, S. G. N. & Komiyama, N. “Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior.” Nature Neuroscience 16 (2013) 25-32. doi:10.1038/nn.3277

  • List of research papers by Seth Grant

  • See FREE transcript for more links and references

  • More episodes about brain evolution: BSP 47, BSP 48, and BSP 51

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

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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 ofsynapse 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 co-opted 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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  • Buy mp3 for $1.

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Addition Show Notes and Links

References:

Blog posts and other links:

Learn more about Dr. Grant's work:

Send email feedback to Ginger Campbell, MD at brainsciencepodcast@gmail.com.