By Jordan Farrell

The brain has a remarkable ability to keep track of where we are in space and form a mental map of our environment. Even when we are not physically moving, we are able to mentally navigate through space independent of our body, such as mentally retracing our steps to the location of our parked car. The mechanisms by which the brain can explore space to create and utilize a mental map, as well as then re-access it in an “offline” state are increasingly being understood. Mounting evidence supports that replaying of neural activity, such as previously experienced events, helps consolidate memories. But how does the brain snap out of replay mode and shift back to the present? This is especially important if something stimulates us in our immediate environment, like hearing our name called.

Using open datasets and data collected during my postdoctoral work with Ivan Soltesz at Stanford University, we found that a characteristic voltage signature called a dentate spike, which is produced by synchronously active neurons in the hippocampus, accompanies this transition to reality. Neurons that tell us where we are in space, called “place cells”, are specifically kicked into high gear during dentate spikes. This realignment of the cognitive map to current reality also occurs if we play a loud tone to wake mice from a restful state. By pairing this loud, aversive tone with a specific location, we could test whether mice can form an associative memory and avoid the aversive location when we blocked dentate spikes. Dentate spikes were necessary for this memory, highlighting that this pattern of brain activation shifts the brain towards engaging with its immediate surroundings.

These findings have inspired several new research avenues in our recently established lab at Boston Children’s aimed at understanding how dentate spikes may be perturbed under pathological conditions, including memory disorders. We are especially interested in how the pronounced brain-wide activity increases that occur during dentate spikes could play a role in driving seizure activity in epilepsy. Our goal is to understand the neural network mechanisms responsible for the generation of dentate spikes in hopes of yielding new approaches for modulating their activity across a range of brain disorders

Jordan Farrell is an Assistant Professor of Neurology at Harvard Medical School and a faculty member of the Rosamund Stone Zander Translational Neuroscience Center and F.M. Kirby Neurobiology Center at Boston Children’s Hospital.

Learn more in the original research article:
Neural and behavioural state switching during hippocampal dentate spikes
Farrell JS, Hwaun E, Dudok B, Soltesz I.. Nature. 2024 Mar 13. Epub ahead of print. PMID: 38480889.