Spatial memories help us navigate to places we want to go. However, scientists still don’t fully understand how our brains store these goal locations or how they help us reach them.
In a new study, Neuroscientists at Johns Hopkins Medicine successfully used a sophisticated brain-imaging system to reactivate a specific memory circuit in mice. This lets the mice find shelter even if no shelter is present.
The study sheds light on how memories are structured in the mammalian brain. It could lead to new ways of slowing down or preventing the memory loss that accompanies Alzheimer’s and other neurodegenerative diseases.
The team stimulated neurons in two areas of mouse brains:
- The nucleus accumbens, aka the brain’s “pleasure center,” plays a key role in relaying dopamine-dependent behaviors.
- The dorsal periaqueductal gray (PAG) has a crucial role in defensive behavior.
How does our brain separate, store, and retrieve memories?
Stimulating neurons in these areas of brain reactivated a “spatial memory”. It leads mice ti seek for shelter, found scientists.
Senior author Hyungbae Kwon, Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine said, “When we artificially reactivate those memory circuits in the brain, it triggers the mouse to do the same thing it did naturally, even without the fear stimuli that cause them to seek shelter to begin with.”
In the experiments, scientists allowed mice to explore their surroundings within a box with shelter in the corner. They added colorful shapes like triangles and circles to help the mice find shelter. After the mice spent seven minutes getting used to the area, they introduced a visual or sound signal to encourage them to look for the shelter, helping the mice build a spatial memory based on their location and the cues.
Usinga light-activated gene-expression switching system called Cal-light, scientists selectively tagged shelter memory neurons. Once these neurons were identified in nucleus accumbens, they switched on expression of the genes associated with them, reactivating the shelter-seeking memory in mice while also activating neurons in the dPAG.
Three regions in our brain store the memories of a familiar place
The mice remembered where the shelter had been and went to that spot even when the shelter and threat were gone. To understand this, scientists activated specific neurons in two brain areas: the nucleus accumbens and the dPAG, to see if activating just one of these areas would trigger the mice’s behavior.
It was surprising for scientists to know mice did not seek out shelter after activating neurons in the nucleus accumbens alone. Activating neurons in the dPAG made the mice act randomly and didn’t lead them to the specific area where they had previously sought shelter.
Kwon said, “The Cal-light system allowed us to selectively tag a specific function in the brain, helping us to map out memory on a cellular level.”
“Eventually, this research could provide a foundation for reactivating or engineering memory circuits in people with Alzheimer’s.”
“If we understand the macro-level structure of memory, then we may be able to develop more effective strategies to prevent or slow down neurodegenerative diseases using this method.”
Scientists noted, “They hope to understand brain-wide memory structure by selectively tagging and reactivating neurons with different functions in different areas of the brain that lead to other specific behaviors.”
“Understanding how all of these memory circuits work together will help us understand brain function better.”
Journal Reference:
- Jung, K., Krüssel, S., Yoo, S. et al. Dopamine-mediated formation of a memory module in the nucleus accumbens for goal-directed navigation. Nat Neurosci (2024). DOI: 10.1038/s41593-024-01770-9