Researchers at the Picower Institute for Learning and Memory at MIT report in the Jan. 24 online edition of Science that they have created a way to see, for the first time, the effect of blocking and unblocking a single neural circuit in a living animal.
This revolutionary method allowed Susumu Tonegawa, Picower Professor of Biology and Neuroscience, and colleagues to see how bypassing a major memory-forming circuit in the brain affected learning and memory in mice.
“Our data strongly suggest that the hippocampal neural pathway called the tri-synaptic pathway, or TSP, plays a crucial role in quickly forming memories when encountering new events and episodes in day-to-day life,” Tonegawa said. “Our results indicate that the decline of these abilities, such as that which accompanies neurodegenerative diseases and normal aging in humans, is likely to be due, at least in part, to the malfunctioning of this circuit.”
Combining several cutting-edge genetic engineering techniques, Tonegawa's laboratory invented a method called doxycycline-inhibited circuit exocytosis-knockdown, or DICE-K-an acronym that also reflects Tonegawa's admiration of ace Boston Red Sox pitcher Daisuke Matsuzaka. DICE-K allows researchers for the first time to induce and reverse a blockade of synaptic transmission in specific neural circuits in the hippocampus.
“The brain is the most complex machine ever assembled on this planet,” Tonegawa said. “Our cognitive abilities and behaviors are based on tens of thousands of molecules that compose several billion neurons, as well as how those neurons are connected.
“One effective way to understand how this immensely complex cellular network works in a major form of cognition like memory is to intervene in the specific neural circuit suspected to be involved,” he said.
Computing memories
The hippocampus, a seahorse-shaped brain region, plays a part in memory and spatial navigation. In Alzheimer's disease, the hippocampus is one of the first regions to suffer damage; memory problems and disorientation are among the disease's first symptoms.
The hippocampus is made up of several regions--CA1, CA3 and the dentate gyrus--that are wired up with distinct pathways.
The MIT study sought to determine how the interactions between neural pathways and the hippocampal regions affect learning and memory tasks.