Switching Memory Systems during Learning: Changes in Patterns of Brain Acetylcholine Release in the Hippocampus and Striatum in Rats

This experiment measured acetylcholine (ACh) release simultaneously in the hippocampus and striatum while rats were trained in a cross maze. Consistent with past findings, rats initially showed learning on the basis of place (i.e., turning to the correct position relative to the room), but after extensive training, rats shifted to learning on the basis of response (i.e., turning to the right/left to find the food). Profiles of ACh release in the hippocampus and striatum were markedly different during training. In the hippocampus, ACh release increased by ∼60% at the onset of training and remained at that level of release throughout training, even after the rats began to show learning on the basis of turning rather than place. In the striatum, increases in ACh release occurred later, reaching asymptotic increases of 30–40%, coincident with a transition from expressing place learning to expressing response learning. These findings suggest that the hippocampal and striatal systems both participate in learning in this task, but in a manner characterized by differential activation of the neural systems. The hippocampal system is apparently engaged first before the striatum is activated and, to the extent the hippocampus is important for place learning, promotes the use of a place solution to the maze. Later in training, although the hippocampus remains activated, the striatum is also activated in a manner that may enable the use of a response strategy to solve the maze. These findings may offer a neurobiological marker of a transition during skill learning from declarative to procedural learning.