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Love it or hate it, the Morris Water Maze is a staple of most memory labs. If you’re a PI, you probably love it. If you’re a graduate student, undergrad, technician, or any other poor soul that actually has to run the damn thing, it’s very likely that you hate it. And for how widespread its use is, it certainly has many, many limitations. Don’t tell me that plunking a rat into a pool of milky water, with an invisible platform as his only means for escape, is a pure measurement of spatial memory. The stress alone is enough to confound your measurement. But as the saying goes, it’s the worst test for spatial memory we have, except for every other test in existence…
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And amidst this backdrop, the creator of the Morris Water Maze, the (in)famous Richard Morris, took the stage for the SfN Presidential Special Lecture last Sunday (Oct 18). Part of me was anticipating some disgruntled grad student start chucking wet rats at the stage, while another was excited to hear the musings from one of the greatest minds in the field. But I began to lose interest in both prospects as he slowly trudged through decades of memory research with his punctilious British accent. I’m glad I held on though, because when past gave way to present, he introduced some very exciting research that challenges what some consider dogma in learning and memory research. Basically, he set out to refute two long-held beliefs by claiming: 1) under particular scenarios, memories can be formed to weak, sub-threshold input (that is, input unable to form a memory by itself); and 2) cortical learning – which is believed to take place only after many repetitions or long durations of time – can be rapidly acquired if new learning is integrated into a previously held network of cortical memories (i.e., an existing schema). The first statement I didn’t find that revolutionary, as we’ve known for a long time that super-threshold stimuli paired with sub-threshold stimuli can cause a memory for the weak stimuli to be formed. However, his interpretation was quite different and actually rather novel. The claim? Memory formation requires both a tag and interacting ligands. The former can be elicited by strong or weak stimulation. In contrast, only strong stimulation can bring about the latter. The evidence? LTP was blocked (via CaMKII inhibition) in strongly stimulated pathways. However, when a weak stimulus was applied at a later time point in a separate pathway, this weakly stimulated synapse was potentiated. The explanation? The strong stimulation causes expression of ligands that interact with CaMKII, leading to LTP. Usually, weak stimulation does not lead to ligand creation (or perhaps ligand liberation). But because the ligands were available due to the previous strong stimulation (and perhaps still present because they were inhibited from binding within the “strong pathway”), they bound to tags present in the weak pathway, leading to potentiation of theses synapses. Beautiful. His second claim employed a clever behavioral paradigm that would take too long to get into here (good news though: it in no way involves water). But the gist is that if animals are able to integrate new information into an existing, well-learned schema, then this new knowledge can be incorporated into the cortex very rapidly. This learning is still hippocampal-dependent, however, as lesioning the hippocampus before or directly after the task abolishes learning. But the role of the hippocampus is remarkably transient (only a day or so, I believe). After delighting us with these recent insights, he moved toward the future of memory research, and, like all great scientists before him, he has set his sights on locating the legendary engram. And while I’m hopeful that he will bring about great advances in this ongoing search, like all great scientists before him, he will probably fail to find it (as I’m sure I will if I ever take up the learning and memory torch that intrigues me so). So, there you have it. Despite creating one of the most hated behavioral tests of our time – and being British – his brilliance and keen intellect is undeniable (just kidding, Brits). No real surprise, of course, but it’s exciting when giants of the field still have some tricks up their sleeve.
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