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For years scientists have sought technological advances to allow them to study the neural pathways in the mammalian brain in more detail. Recently, it became possible to pin-point specific neural circuits. Robert Malenka, of Stanford University in California, and his postdoc Anatol Kreitzer studied two related pathways, and their findings could contribute to the development of therapies for disorders such as Parkinson's disease. They focused on neurons in the striatum, a brain region involved in two circuits — one that promotes movement and one that inhibits unwanted movement. These processes are modulated by endocannabinoids, whose release from striatal neurons is promoted by dopamine. Dopamine is depleted in Parkinson's disease. Malenka and Kreitzer proposed that restoring normal function to the circuit that inhibits unwanted movement could improve motor control (see page 643). It is too early to tell whether an effective therapy for Parkinson's disease will emerge, but the authors show that two drugs — one that inhibits the normal breakdown of endocannabinoids and one that mimics dopamine — can drastically improve motor function in dopamine-depleted mice.

How did you isolate specific brain pathways?

Transgenic mice engineered with fluorescent markers for different subtypes of neurotransmitter receptor make it possible to distinguish between different circuits, such as the two pathways in the striatum. We couldn't have done this work without such mice.

Are plant-derived cannabinoids, such as those in marijuana, a treatment option?

Probably not. The drugs we used are very different from marijuana. We boosted the action of endogenous cannabinoids in specific pathways. But the primary cannabinoid receptor is found in nerve terminals all over the brain, and taking marijuana activates all of them indiscriminately.

What new questions do your findings raise?

The action of dopamine in the striatum has been the subject of intense interest and controversy for the past 30 years. We're just beginning to make significant progress in understanding its many different physiological effects. Our work looks at just one of dopamine's many actions in the brain.

What is the future of neuropharmacology?

With gene-expression maps and the ability to engineer transgenic mice encoding cell-specific activity markers, it is hoped that we'll be able to selectively study and manipulate specific circuits in the brain in a much more sophisticated way. This might, in turn, lead to the development of new pharmacotherapies.