Thus, in essence, the entire brain is an intricate interval timing machine, in which individual structures busy with their own neural tasks, generate resonances that integrate to become ticks of the neural clock.
Meck, Buhusi and their clockwork colleagues are using an array of experimental techniques to try to identify this "baton" timing signal and to refine the theory. These include studies using genetically modified mice, pharmacological tools, recording of electrical brain signals in ensembles of brain cells and functional magnetic resonance imaging of the brain.
For example, they are studying how the clock's ticking changes in Parkinson's patients as they change levels of their medication, which effects the amount of dopamine in their brains. Dopamine has been implicated as a key signaling molecule in the neuronal circuitry of the timing machinery.
"When Parkinson's patients are on their medication, they time quite normally," said Meck. "But as their medication wears off, we can see their clock slow down by recording their brain signals."
Said Meck of their research, "We're addressing two challenges. One is to find the molecular processes that underlie this internal clock. And the second challenge is to build more realistic models of how this timing process works, with constant, parallel input from throughout the brain." In such studies, the researchers face the daunting process of trying to monitor the intricate swirling of neural activity throughout the entire brain, said Meck.
"Looking at only one place in the brain for the interval clock is like the blind man feeling just the toe of the elephant and trying to describe how it works," he said. "While we're very excited about our success so far, we