The hippocampus is a neural structure thought to maintain a cognitive map of our surroundings and the activity of some hippocampal neurons reflect when an animal is in a particular location. These ‘place cells’ are thought to represent the cognitive unit which signals the representation of location in space.
Sleep is thought to contribute to memory consolidation, and observed patterns of neural activity are known to repeat as sharp wave ripples (SPW-Rs) during slow wave sleep. However, it is unknown if these SPW-Rs during sleep actually reflect a replay of spatial information or not. In a recent publication in Nature Neuroscience (de Lavilleon et al., 2015), the authors investigate this by dissociating neural activity from the physical location of mice and demonstrating causally that place cell activity is representative of location.
In the work, the researchers used in vivo recordings of hippocampal principal cells and stimulation of the medial forebrain bundle (MFB), a fiber tract which includes dopaminergic projections and is involved in reward signaling. First, they demonstrated that MFB stimulation did not interrupt sleep, hippocampal theta rhythms, place cell characteristics, or SPW-Rs. Then they used an online detection algorithm which allowed them to detect place cell spiking and immediately stimulate the MFB. As expected, when mice received MFB stimulation while in a particular area of an open field, the animals sought out and remained within that area, so as to continue to receive the rewarding stimulation. Critically, after MFB stimulation, the mice continued to seek out and spend time in that location, demonstrating a conditioned preference for that space.
In a follow up test, place cells were identified while a new set of mice navigated the open field. Researchers continued to monitor the mice as they slept, and stimulated the MFB when SPW-Rs were detected, pairing the neural activity of the place cell with the rewarding activity of MFB stimulation. When these mice were awake and placed back into the open field, they spent a significant amount of time (4-5 times pre-stimulation) in the area where the place cell was most active. Additionally, MFB-stimulated mice were quicker to move to the place cell area, spent more time there and spent less time elsewhere in the arena, compared to controls.
These results causally demonstrate that place cell activity represents spatial representations. Additionally, memories made during sleep show a role for spatial reactivation of place cells in the consolidation of spatial memory. This represents a critical step forward in our understanding of memory consolidation.
- de Lavilleon G, Lacroix MM, Rondi-Reig L, Benchenane K (2015) Explicit memory creation during sleep demonstrates a causal role of place cells in navigation. Nature Neuroscience, advance online publication. doi: 10.1038/nn.3970