To find out, the team used a technique developed in Harvey’s lab that places mice in a virtual reality maze : A mouse runs on a ball as it looks at a large, surround screen that displays a spatial navigation task such as solving a maze to find a reward. The investigators wondered whether Fos could be involved in how mice form spatial maps as they navigate their environment. However, the relationship between Fos and place cells in the hippocampus was not known.
They also demonstrated that Fos acts as a mediator for different types of neural plasticity, including navigation and memory formation. In previous research, Greenberg and his colleagues showed that Fos is expressed minutes after a neuron is activated, making it a useful marker for neural activity in the brain. Greenberg’s lab studies the Fos gene, which codes for a transcription factor protein that regulates the expression of other genes. To study the molecular cascade involved in this mapping process, Harvey and first author Noah Pettit, research fellow in neurobiology in the Harvey lab, teamed up with co-senior author Michael Greenberg, the Nathan Marsh Pusey Professor of Neurobiology at HMS, and author Lynn Yap, a graduate of the Harvard PhD Program in Neuroscience who did her doctoral work in the Greenberg lab. “My lab has studied spatial navigation for years, including how place cells form a map of the environment and form spatial memories,” Harvey said, and yet “the molecular mechanisms that underlie those processes have been difficult to study in the behaving animal.” By turning on and off as an animal moves through its environment, place cells essentially construct a map of the surrounding area that can be incorporated into a memory. Scientists have long known that for navigation, the hippocampus contains specialized neurons called place cells that selectively become active when an animal is at different locations in space. The hippocampus lies deep in the brain’s temporal lobe and plays an essential role in learning, memory, and navigation for many species, including mice and humans. Eventually, this knowledge could help scientists better understand what happens when this process breaks down, as it often does as a result of brain injury or neurodegeneration. If the findings translate into humans, they will provide crucial new information about how our brains construct spatial maps. “Here we can understand what’s actually underlying the formation and stability of spatial maps.” “This research connects across the different levels of understanding to make a pretty direct link between molecules and the function of circuits for behavior and memory,” said senior author Christopher Harvey, associate professor of neurobiology at HMS.
24 in Nature, establishes that a gene called Fos is a key player in spatial mapping, helping the brain use specialized navigation cells to form and maintain stable representations of the environment. The new study, conducted in mice and published Aug. Now, scientists, through a multilab collaboration within the Blavatnik Institute at Harvard Medical School, have made a major advance toward understanding the molecular mechanisms that are involved in the creation of spatial maps in the brain. Perhaps unsurprisingly, the precise steps of this multiplayer interaction have eluded neurobiologists.
Just how the brain forms these spatial maps is astoundingly complex – a process that involves an intricate molecular interplay across genes, proteins, and neural circuits to shape behavior.
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