Rapid spatial cognition in mice, with and without neocortex and hippocampus

Abstract Rapid learning, memory, and generalization are often attributed to circuits of the neocortex and hippocampus, but their specific role remains unclear. To examine these cognitive abilities together in individual mice, we observed mice navigating the Manhattan Maze , a reconfigurable 3D labyrinth. Naïve wildtype mice improved within two rewards, approached efficient paths within ∼20 rewards, retained a 9-turn route overnight, and learned faster in new configurations. Much of the few-shot improvement follows from a rule-based forward bias that emerged even before any reward. In a maze with loops, where that rule is less useful, mice learned within a few rewards to prefer one bottleneck corridor far from the reward location, while choices elsewhere stayed flexible. To begin linking these different components of learning to brain function, we presented the same task to mutant mice that lack the hippocampus and most of the neocortex. They were impaired during initial exploration, where repetitive scanning made them ∼3× slower to obtain the first few rewards. Past that stage, learning, retention over weeks to months, and generalization to new mazes were largely preserved. Learning this fast is hard to reconcile with trial and error, in which value propagates backwards from the reward. A neuromorphic circuit model instead accounts for the bottleneck choice: it builds a map of the environment without reward, and needs neither cortical nor hippocampal circuit motifs. Therefore, learning is possible without the involvement of neocortex and hippocampus. Structure learned before the first reward, rather than the reward itself, may be what makes few-shot learning possible.