Stimulating Neurons With Light
One of our most important strategies for understanding brain functioning is electrical stimulation. But this technique activates a single neuron with a microelectrode or all of the neurons surrounding a larger electrode—regardless of their function. Optogenetics promises a variety of advantages, including targeting an entire network. Optogenetics involves insertion of a gene in neurons to create light-activatable ion channels in the neural membrane. Channel rhodopsins, normally produced by algae and used to orient toward light, can be activated by blue light; they allow entry of positive ions, depolarizing the neuron. Halorhodopsin provides a chloride pump; activating it with yellow light hyperpolarizes the neuron. Both can be inserted in a group of neurons if needed, and the neurons can be excited and inhibited in intervals of just a few milliseconds. (See PLoS ONE , Vol 2, e299.) Even better, the gene insertion can be targeted to specific networks of neurons, for example those employing dopamine. Neurons can be stimulated by light on the exposed surface of the brain if they are not too deep, or a light-conducting optical fiber can be inserted into deeper structures. Optogenetics has been used to study sleep-producing circuitry in the hypothalamus (Nature, Vol 450, 420-425); to restore some visual functioning in mice lacking visual receptors, by inserting channel rhodopsin in neurons at the back of the eye (Nature Neuroscience , Vol 11, 667-675); and to pin down just which neurons account for the effect of deep brain stimulation for Parkinson's disease, helping explain why some patients receive no benefit (Science, advance online publication, DOI: 10.1126/science.1167093). The technique could eventually find therapeutic uses, but currently such gene manipulation research is prohibited with human subjects.
A New Way to Separate Nature from Nurture
In Chapter 5 you will learn that children whose mothers smoked during pregnancy have double the rate of conduct disorder. It seems logical that this effect is due to the mother's smoking, but we can't rule out the possibility that it stems from some genetic difference in women who are prone to smoke—however far-fetched that might seem. To study this question in animals we would use cross-fostering, in which an egg or fetus from an unrelated mother is implanted in the female that will bear the offspring. Of course, that strategy is not available to us with humans, but the increasing frequency of in vitro fertilization (IVF) provides a very promising alternative. British researchers examined the medical records of 800 children conceived with IVF, about a quarter of whom were genetically unrelated to the mother. Children born of mothers who smoked during pregnancy weighed 11.4% less than children of non-smoking mothers, regardless of genetic relationship, indicating that this effect is environmental. On the other hand, antisocial behavior (tantrums, fighting, lying, etc.) increased in smoking mothers, but only if the mother and child were related, suggesting that this effect has genetic rather than environmental roots. Proceedings of the National Academy of Sciences, Vol 106, 2464-2467.
Will the EU Ban Primate Research?
The European Union is revising its animal research regulations for the first time since 1986. Last year, the European Parliament passed a resolution calling for a ban on all use of nonhuman primates; however, the European Commission, which is the union's executive body, is proposing only an end to scientific "procedures" on great apes and a ban on the use of wild-caught primates. Since no medical research has been performed on great apes in the EU since 2002, many see the first of these two proposals as a token move. The proposal, now in the draft stage, emphasizes the "3Rs" of reducing the number of animals used, refining techniques to lessen pain and discomfort, and replacing animal studies with alternatives. And, if the rules are adopted, for the first time they will cover non-human fetal vertebrates in the third trimester of their development, along with invertebrates that show evidence of sign and distress, such as octopuses and lobsters. ScienceNow Daily News, 11/5/08.
