0
0
Madrid, Spain – A groundbreaking study has revealed new insights into how the brain forms internal “maps” to help navigate and remember the world. Led by Liset M. de la Prida at the Cajal Neurosciences Center (CNC-CSIC) in Madrid, in collaboration with Imperial College London, the research sheds light on how spatial and experiential information is encoded in the hippocampus, a crucial brain region for navigation and memory.
Published today in Neuron, the study demonstrates that two distinct types of hippocampal neurons work together in mice to generate sophisticated and adaptable spatial maps. The findings could have significant implications for understanding neurological disorders related to memory and orientation, such as Alzheimer’s disease.
Neurons That Work in Harmony
The researchers identified two subpopulations of pyramidal neurons—superficial and deep—each playing a unique role in processing spatial information. Deep pyramidal neurons respond to changes in the immediate environment, such as the movement of objects like furniture, while superficial pyramidal neurons maintain a stable spatial representation, anchored to global features like walls, windows, and doors.
“This stability is crucial for maintaining a consistent reference of the environment,” said de la Prida. The study builds upon previous work recognized with the 2014 Nobel Prize, awarded to May-Britt and Edvard Moser and John O’Keefe, who discovered place and grid cells, the fundamental elements of the brain’s positioning system.
Speed, Space, and Direction
To analyze these representations, the research team used maze-like corridors where mice navigated through visual and tactile cues. The results showed that deep-layer neurons are more attuned to movement, speed, and direction, responding strongly to nearby landmarks. In contrast, superficial neurons process the broader spatial environment, allowing for a cohesive and adaptable mental map.
“Hippocampal neurons create abstract spatial representations that enable orientation and memory,” de la Prida explained. “Until now, it was unclear how different neuron types contributed to these maps.”
Advanced imaging techniques played a crucial role in these discoveries. Researchers used a dual-color sensor system to track both superficial and deep neurons in real time. “This method allowed us to visualize hundreds of neurons simultaneously and understand their interactions,” said co-author Juan Pablo Quintanilla.
Updating Maps in Real Time
The study also incorporated topological mathematics to analyze neuronal maps, revealing that as mice explored, their hippocampal maps took the shape of three-dimensional rings. When environmental changes occurred—such as furniture being rearranged—the two neuron types responded differently, ensuring the brain could update its spatial representation without losing overall coherence.
“These different spatial representations coexist in parallel within the hippocampus,” said biomedical engineer Julio Esparza, who led the topological analysis. “This ability to maintain multiple reference frames is a remarkable feature of cognitive maps.”
Using chemogenetics, researchers temporarily silenced specific neuron types to observe how spatial maps could be rotated and reoriented. The findings suggest that similar mechanisms could be used to enhance memory retention, such as through the ‘memory palace’ technique, which leverages spatial visualization for recall.
Implications for Neurological Research
The study’s findings provide a deeper understanding of how the hippocampus integrates different frames of reference to process spatial information. This could pave the way for future treatments targeting memory-related disorders like Alzheimer’s disease, where spatial disorientation is a common symptom.
“These discoveries help us understand how our brains build and maintain internal maps of the world,” said Esparza. “It could have real-world applications for treating neurodegenerative diseases.”
More Information: Julio Esparza et al, Cell-type-specific manifold analysis discloses independent geometric transformations in the hippocampal spatial code, Neuron (2025). DOI: 10.1016/j.neuron.2025.01.022
Disclaimer: This article is based on scientific research findings and is intended for informational purposes only. The study is conducted on animal models, and its implications for human neurological treatment require further research and clinical validation.
