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
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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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.
When I started preparing for this week's episode I realized that before I could discuss neurotransmitters (brain chemicals) I would need to discuss some basic information about how neurons work. Thus this episode is rather long and technical, but hopefully understandable to those who are new to the field. I am including more detailed show notes than I usually do, along with the approximate times for the main sections, in case there is a particular topic you want to go back and review.
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The main source for this episode was the textbook, From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System, Fourth Edition (2001)
2:39-11:33 Neuronal signaling-the basics of electrical and chemical signaling types of signaling-electrical and chemical introducing the synapse the importance of membrane proteins
11:55 - 13:03 A bried discussion of how the brain differs from a digital computer
13:3 3-13:50 Definition of neurotransmitters-
13:56 -22:10 How neurotransmitters interact with receptors in the synapse
-direct and indirect chemical synapses-why they are important
-neuromuscular junction-an example of a direct chemical synapse
-the importance of synaptic delay
-the role of second messengers in indirect chemical synapses
-release and recycling of neurotransmitters
22:25 -29:42 Types of Neurotransmitters and how they work-with examples
-how neuropeptides differ from low molecular weight neurotransmitters
-a little about how drugs work
29:58 - 41:54 How Neurotransmitters function in the Central Nervous System-with examples
-Glutamate is the key excitatory neurotransmitter in the brain
-an aside about Nutrasweet™ (30:33)
-glycine and GABA are inhibitatory
-discussion of Molecules of Emotion by Candace Pert (35:30-36:55)
-dopamine and Parkinson's disease
42:07 - 43:36 Closing Summary