PASADENA, Calif.- Biologist Erin Schuman is interested in how memories are formed--or forgotten. The landscape the professor of biology at the California Institute of Technology explores is the hippocampus, the part of the brain known to be crucial for memory in humans and other animals.
In 2002, Schuman and Miguel Remondes, her graduate student, published a paper in the journal Nature that suggested a possible role for a well-known but poorly understood part of the brain known as the temporoammonic (TA) pathway. Using rat hippocampal slices, they suggested two possible roles for the TA pathway that were not previously known: to serve as a memory gatekeeper that can either enhance or diminish memories, and to provide information to help animals know where they are in their environments.
The researchers' next step was to prove their theories by looking at a possible role for the TA in memory at a behavioral level. That is, says Remondes, now a postdoctoral fellow at MIT, "to do the real test."
To understand how memories are formed, many scientists have focused on the "trisynaptic circuit," which involves three areas of the hippocampus: input from the senses is first sent from the cortex to the dentate gyrus, where this signal is processed by two sets of synapses, then sent back to the cortex. That's the circuit. An often overlooked separate input to the hippocampus, though, is the TA pathway. It makes direct contact with the neurons that are at the last station in the trisynaptic circuit, thus short-circuiting the traditional trisynaptic pathway.
Reporting in the October 7 issue of the journal Nature, Remondes and Schuman, also an associate investigator for the Howard Hughes Medical Institute, now show they were correct in their belief that the TA Pathway is important in spatial or location memory. The scientists used rats as their experimental animal, and the Morris Water Maze, a standard test for location memory in rodents. The animals swim in a pool of opaque water until they find a hidden goal--a platform which allows them to escape the water. To find the platform, the animals rely on the geometrical relationships of cues away from the pool (e.g., on the walls of the maze). In other words, says Remondes, "they have to navigate and remember where the platform is in order to escape the water."
The researchers tested both short-term (24 hours) and long-term memory (four weeks). The TA pathway was lesioned (disabled) in one set of rats; another set was used as a control. Having learned the location of the platform, both sets of rats still remembered where it was 24 hours later. But when tested four weeks later, only the control rats remembered where it was. The lesioned rats forgot, which showed that the TA pathway played some role in the retention of long-term memories. But what was the role?
"It led to a second question," says Schuman. "Because long-term memories require something called consolidation, an exchange of information between the cortex and hippocampus, we wanted to know if the TA pathway was working in the acquisition phase of memory or in its consolidation."
Using two other groups of rats, the pair conducted a second set of tests. After confirming the rat's memory of the platform after 24 hours, one group was immediately lesioned. These animals lost their long-term memory when tested 4 weeks later, indicating to Schuman and Remondes that ongoing TA pathway activity was required on days after learning to stabilize or consolidate the long-term memory.
The second group of rats was also lesioned, but not until three weeks later. The researchers found that this group remembered the platform's location, showing their memory had already been adequately consolidated after three weeks. This proved the TA pathway is required to consolidate long-term location memory.
"These data indicate there must be a dialogue between the hippocampus and the cortex during long-term memory consolidation," says Schuman. "Clearly, the TA pathway plays an important role in this discussion." Further, she notes, "understanding the mechanisms of memory formation and retention may shed light on diseases like Alzheimers, where memory is impaired. "
