Nestled deep in the brain, the hippocampus is the seat of spatial cognition. Specialized hippocampal neurons fire in consistent patterns thought to construct mental maps that help us navigate the world—in general, researchers believed there was one map for every external physical environment. But new findings call into question that assumption, overturning a long-standing textbook dogma. In work published in Current Biology, researchers suggest that hippocampal neurons can actually encode multiple maps of the same environment.
Researchers at the Weizmann Institute of Science in Rehovot, Israel, tracked the activity of hundreds of hippocampal mouse neurons over time. Each of 37 mice ran back and forth on a linear track—in the course of 25 to 40 trials spread over multiple days—with a tiny microscope affixed to its head. The microscope peered into the hippocampus through a probe in the brain and recorded the activity of individual neurons. The researchers removed each mouse from the track for three minutes between trials so that the mouse visually disconnected from the track environment, letting its neurons “reset” between trials.
As expected, the microscope detected specialized hippocampal neurons called place cells firing in sequence as each mouse ran along the track. For example, in the hippocampus of one mouse, place cell one was active when the mouse reached the middle of the track running in a rightward direction, while place cell four fired when the mouse was at the far end of the track. Place cells have long been known to anchor the brain’s positioning system, building a mental map that many animals use to navigate. The general assumption had been that one location—an office, kitchen, or, in this case, a mouse-sized track—is associated with one map.
Hence, the authors of the Current Biology study expected that each mouse place cell would retain its preferred firing position across trials and days, building a single map—place cell one, for example, might always fire when the mouse reached the middle of the track, explains coauthor Yaniv Ziv, a neurobiologist at the Weizmann Institute. Indeed, the researchers observed this pattern in some mice. But other mice defied expectations with place cells that switched their preferred firing position between trials. For example, in the hippocampus of a particular mouse in this study, place cell one fired in the middle of the track during trials one, two, and four, but activated at the far right of the track during trials three and five.
At first, Ziv thought the switching was erroneous, that each mouse had one true map, and that any incongruent place cell activity was random. But when he and coauthor Alon Rubin, also of the Weizmann Institute, examined the results, they saw that whole patterns of place cells consistently and synchronously switched their firing positions between trials. It seemed that place cells could switch among several modes, thereby building multiple maps of the same environment.
Some previous studies had in fact shown that animals can make multiple hippocampal maps for the same place under some circumstances, says Edvard Moser, cowinner of the 2014 Nobel Prize in Physiology or Medicine for the discovery of the brain’s positioning system. But Moser, at the Norwegian University of Science and Technology in Trondheim, says that these previous studies only showed multiple maps in cases where the animals were old, mentally impaired, or tricked into thinking that they were experiencing two different environments. Experiments reported in the place cell literature, going back to the 1970s, typically followed the activity of fewer neurons over much shorter periods, notes computational neuroscientist Sandro Romani of the Howard Hughes Medical Institute Janelia Research Campus in Ashburn, Virginia. More recently, labs have collected data from many neurons across days, he says. Revisiting that data could perhaps shed light on the conditions under which researchers observe multiple maps.
Romani adds that the discovery could help researchers better understand how the hippocampus stores memories. “I might have memories about the room I’m in now that could be from yesterday, two weeks ago, five years ago, but this room is always the same,” he says. “Having a system like this that creates different maps could help in making these memories more distinct. And generally, the more distinct the memories, the more you can store.”
The study also raises new questions, including how different mental maps for the same environment emerge in the first place. “The hippocampus may choose among multiple available more or less premade maps when the animal first encounters a place,” Moser offers by email.
It’s still unclear why a mouse would want multiple maps of the same environment, coauthor Ziv notes. Future work will probe whether there’s some functional utility to having more than one map.