Learning by Subtraction: Hippocampal Activity and Effects of Ethanolduring the Acquisition and Performance of Response Sequences

摘要

Learning is believed to be reflected in the activity of the hippocampus. However, neural correlates of learning have been difficult to characterize because hippocampal activity is integrated with ongoing behavior. To address this issue, male rats (n=5) implanted with electrodes (n=14) in the CA1 subfield responded during two tasks within a single test session. In one task, subjects acquired a new 3-response sequence (acquisition), whereas in the other task, subjects completed a well-rehearsed 3-response sequence (performance). Both tasks though could be completed using an identical response topography and used the same sensory stimuli and schedule of reinforcement. More important, comparing neural patterns during sequence acquisition to those during sequence performance allows for a subtractive approach whereby activity associated with learning could potentially be dissociated from the activity associated with ongoing behavior. At sites where CA1 activity was closely associated with behavior, the patterns of activity were differentially modulated by key position and the serial position of a response within the schedule of reinforcement. Temporal shifts between peak activity and responding on particular keys also occurred during sequence acquisition, but not duringsequence performance. Ethanol disrupted CA1 activity while producingrate-decreasing effects in both tasks and error-increasing effects that weremore selective for sequence acquisition than sequence performance. Ethanol alsoproduced alterations in the magnitude of modulations and temporal pattern of CA1activity, although these effects were not selective for sequence acquisition.Similar to ethanol, hippocampal micro-stimulation decreased response rate inboth tasks and selectively increased the percentage of errors during sequenceacquisition, and provided a more direct demonstration of hippocampal involvementduring sequence acquisition. Together, these results strongly support the notionthat ethanol disrupts sequence acquisition by disrupting hippocampal activityand that the hippocampus is necessary for the conditioned associations requiredfor sequence acquisition.