Life without Cortex

In humans, the neocortex (CTX) plays essential roles in sensory processing and motor control. Furthermore, the interplay between the neocortex and hippocampus (HPC) is necessary for the formation, retention, and recall of memories. It is commonly assumed that this applies to rodents as well. Here we tested these ideas using a mouse mutant that lacks the dorsal forebrain, including the hippocampus and most of the neocortex. We studied the acortical (ACT) mutant in four naturalistic tasks: escape from predator, hunting of prey, navigation in a complex labyrinth, and long-term memory ranging from hours to weeks. Some of the experiments were repeated on mice with acute lesions to the cortex and hippocampus. We found that ACT mice are proficient in all these behaviors. On tasks that require learning, they take ~3x longer to mastery than normal mice. For example, the ACT animals - like normal mice - exhibit one-shot learning of a reward location in a complex maze. However, it takes them longer to discover that location. As a rule, the ACT mouse’s behavior includes more repetition and less exploration. In addition, we found a few specific deficits: clumsy manipulation with the digits of the forepaw, and a failure to transition from escape to sheltering during predator avoidance. Both deficits are expected based on known cortical pathways. We conclude that the neocortex and hippocampus are not necessary for escape, pursuit, navigation, or learning. The absence of CTX/HPC introduces behavioral changes that slow the learning process but do not eliminate learning or memory itself. Our findings call attention to the power of subcortical pathways in all these functions. We conclude that rodents use CTX/HPC in ways that are categorically different from primates, which recommends caution when translating human psychiatric disorders to mice.