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.Read More
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.Read More
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.
How to get this episode:
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
Upcoming Episode will feature the return of Olaf Sporns (BSP 74) and Dr. Allen Frances, author of Saving Normal: An Insider's Revolt Against Out-of-Control Psychiatric Diagnosis, DSM-5, Big Pharma, and the Medicalization of Ordinary Life and Essentials of Psychiatric Diagnosis, Revised Edition: Responding to the Challenge of DSM-5®.
I (Dr. Campbell) will be at the University of Florida November 1-5, 2013 attending the meeting of the National Association of Science Writers. Drop me an email at firstname.lastname@example.org if you would like to have a meet up.
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.
How to get this episode:
Addition Show Notes and Links
- "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:
Send email feedback to Ginger Campbell, MD at email@example.com.