Monday, May 04, 2009

"Once more into the breach, dear friends, once more!"

The more I read about "Cognitive Computing", the more disenchanted I get with most of the work being done under this banner. There is an awful lot of hype going on here: everything from university researchers that claim how simple it is to create a silicon chip that accurately emulates millions of neurons and projects to create silicon prosthetics for some of the major centers in the brain to overly ambitious claims stating how close we are to getting computers to 'think' and thus to the resulting 'singularity'. Most 'cognitive computing' efforts seem to miss the point that there is more happening here than simple electrical signaling over a network. So coming across the following articles and podcast was like a breath of fresh spring air:

Complex Synapses Drove Brain Evolution:

ScienceDaily (June 9, 2008) — One of the great scientific challenges is to understand the design principles and origins of the human brain. New research has shed light on the evolutionary origins of the brain and how it evolved into the remarkably complex structure found in humans.

The research suggests that it is not size alone that gives more brain power, but that, during evolution, increasingly sophisticated molecular processing of nerve impulses allowed development of animals with more complex behaviours. The study shows that two waves of increased sophistication in the structure of nerve junctions could have been the force that allowed complex brains - including our own - to evolve. The big building blocks evolved before big brains.

Current thinking suggests that the protein components of nerve connections - called synapses - are similar in most animals from humble worms to humans and that it is increase in the number of synapses in larger animals that allows more sophisticated thought. "Our simple view that 'more nerves' is sufficient to explain 'more brain power' is simply not supported by our study," explained Professor Seth Grant, Head of the Genes to Cognition Programme at the Wellcome Trust Sanger Institute and leader of the project. "Although many studies have looked at the number of neurons, none has looked at the molecular composition of neuron connections. We found dramatic differences in the numbers of proteins in the neuron connections between different species".

"We studied around 600 proteins that are found in mammalian synapses and were surprised to find that only 50 percent of these are also found in invertebrate synapses, and about 25 percent are in single-cell animals, which obviously don't have a brain." Synapses are the junctions between nerves where electrical signals from one cell are transferred through a series of biochemical switches to the next. However, synapses are not simply soldered joints, but miniprocessors that give the nervous systems the property of learning and memory. Remarkably, the study shows that some of the proteins involved in synapse signalling and learning and memory are found in yeast, where they act to respond to signals from their environment, such as stress due to limited food or temperature change.

"The set of proteins found in single-cell animals represents the ancient or 'protosynapse' involved with simple behaviours," continues Professor Grant. "This set of proteins was embellished by addition of new proteins with the evolution of invertebrates and vertebrates and this has contributed to the more complex
behaviours of these animals.

"The number and complexity of proteins in the synapse first exploded when muticellular animals emerged, some billion years ago. A second wave occurred with the appearance of vertebrates, perhaps 500 million years ago."

There's an excellent podcast interview with Dr. Seth Grant at BrainScience - episode 51 that covers this work in more depth. Highly recommended!
The ancestral proteins that are found in unicellular animals are the proteins that are found in more or less all of the different synapses in the brain of the mouse. The most recently evolved proteins - the vertebrate proteins - those are the ones that are most diverse in the brain regions of the mouse. So some of those proteins are very high, for example, in the frontal cortex, others might be high in the hippocampus, others might be high in the cerebellum; in other words, they're very variable like that.

So what that is telling us, then, and I'm just returning now to that ancient vertebrate synapse that arose before big brains, it tells us that 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. And we know from many many studies that the regionalization of the brain - there's parts involved with learning, there's parts involved with fear, there's parts involved with some aspect of mood or so on, there's parts involved with motor function - that all appears to be built on the template of molecular evolution of the synapse. "

Journal References
Nature Neuroscience, 8 June 2008 Evolutionary expansion and anatomical specialization of synapse proteome complexity.
Emes RD, Pocklington AJ, Anderson CNG, Bayes A, Collins MO, Vickers CA, Croning MDR,
Malik BR, Choudhary JS, Armstrong JD and Grant SGN.

PubMed Abstract:Neurotransmitters drive combinatorial multistate postsynaptic density networks.
Coba MP, Pocklington AJ, Collins MO, Kopanitsa MV, Uren RT, Swamy S, Croning MD, Choudhary JS, Grant SG.

The mammalian postsynaptic density (PSD) comprises a complex collection of approximately 1100 proteins. Despite extensive knowledge of individual proteins, the overall organization of the PSD is poorly understood. Here, we define maps of molecular circuitry within the PSD based on phosphorylation of postsynaptic proteins. Activation of a single neurotransmitter receptor, the N-methyl-D-aspartate receptor (NMDAR), changed the phosphorylation status of 127 proteins.

Stimulation of ionotropic and metabotropic glutamate receptors and dopamine receptors activated overlapping networks with distinct combinatorial phosphorylation signatures. Using peptide array technology, we identified specific phosphorylation motifs and switching mechanisms responsible for the integration of neurotransmitter receptor pathways and their coordination of multiple substrates in these networks. These combinatorial networks confer high information-processing capacity and functional diversity on synapses, and their elucidation may provide new insights into disease mechanisms and new opportunities for drug discovery.

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