Saturday, January 15, 2011

The crazy present/future cellular mapping

I am fascinated by brain imaging and electrophysiological stimulation, mainly because of the way in which it allows us to have a more minute understanding of the processes involved in functioning. The more micro we can get with these sorts of tests, the more we can actually understand the cellular and molecular mechanisms governing mental processes and behaviours. I read an article recently in Nature ("Neuroscience: Illuminating the brain", Buchen, 2010) about optogenetic manipulation, which is the opening of ion channels through opsin proteins injected via a virus; light stimulation triggers these opsin proteins at the cell membrane to open ion channels. This is a really neat new way of determining, with a great deal of specificity, the cellular networks involved in certain processes, and even crazier than that, the individual activity of cells within those networks. At this time, the light source is implanted through an "optrode" (an optic fibre and an electrode) into the skull of the animal when done in vivo, so there is no application for this on humans. As such, the more tantalizing higher functions we so desperately desire to map are still out of reach; but the neural networks involved in processes such as spatial learning can be measured in mice and rats. Optogenetic manipulation is also used quite successfully in vitro, which is actually how it was discovered. In 2005, Karl Diesseroth and Ed Boyden at Stanford University inserted a light sensitive channel (channelrhodopsin2) from green algae into neurons in a growing dish. They exposed these neurons to a pulse of blue light, and the channels opened, flooding positive ions into the neurons and causing them to fire. Optogenetic manipulation is going to change the mapping of cellular networks in a huge way.

Another thing that's going to change neurological mapping is that crazy connectome! If you haven't seen the TED talk on it (Sebastian Seung: "I am my connectome"):



My problem with this, other than the fact that the talk itself comes off as being a motivational speech, is that it doesn't seem to take synaptic plasticity into account. In fact, what it really doesn't take into account are the individual differences that arise from synaptic plasticity; but most importantly, that we, living our lives, are constantly altering the strength and weakness of connections in our brain. These neural connections are ever-changing and plastic. With every trafficked AMPA, with every hippocampal place cell reorganized, our synaptic circuitry is changing. Yes, it is ever-so-slight, but when what you are measuring is cells, ever-so-slight is pretty huge.

On the other hand, the idea of it being used to visualize mental illness by identifying miswiring of individual connections is pretty wild.

References

Buchen, L. (2010). Neuroscience: Illuminating the brain. Nature 465, 26-28.

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