How does the brain accumulate cognitive maps?

Project Summary Across our lifetimes we have an infinite number of experiences that are stored in our memories. As we age our capacity to reuse this information to influence our future learning decreases, leading to impaired cognitive and behavioral flexibility. Cognitive decline is a major concern for an increasingly large and aging population, and these cognitive deficits will directly impact quality of life for countless individuals. It is essential to understand the neuronal coding deficits underlying cognitive decline to provide the necessary groundwork for developing therapeutic interventions that can spare people from cognitive decline. It has been postulated that the brain uses cognitive maps, or internal neural representations, to enable flexible behavior and relate items in our memory. The discovery of neurons in the hippocampus that fire action potentials in specific locations within an environment, termed place cells, provided initial support for the cognitive map hypothesis, as these cells create a neural representation of the environment. Both the engram and spatial navigation literatures have shown that distinct cognitive maps are used to encode two different environments, which would presumably reduce interference between maps during recall. However, recent work suggests that linking two distinct memories neuronally can enhance memory strength by sharing neural resources. Due to this linking, recall of one memory leads to a higher probability of recalling the other. This implies that some aspects of the two cognitive maps have increased in similarity and are no longer distinct. Others have hypothesized that increased similarity between cognitive maps may link experiences across environments and provide a mechanism to increase learning rates. Indeed, more recent evidence showed that neuronal representations in dCA1 became more similar as mice increased their speed of learning novel problems, suggesting that, under certain conditions, cognitive maps in the hippocampus may become increasingly similar, impacting learning. I will utilize in vivo calcium imaging with miniature microscopes as young adult and middle-aged mice navigate four distinct circular tracks for water rewards to ask the question of whether the similarity between neural representations underlying cognitive maps changes as mice increase their learning rates in novel environments. By using separate measurements of representational similarity, I can provide a detailed account of how the brain encodes new cognitive maps and whether the brain relates cognitive maps to alter learning rates. By using young adult and middle-aged mice, I can determine if these mechanisms change during aging. All results from this proposal have the capability to inform us on how the brain uses stored information to influence our future learning and, ultimately, how these mechanisms change during the early stages of cognitive decline.