Correlates of motivation and reward

Ikemoto, Satoshi

Abstract

To understand how goal-directed behavior is learned, we must first understand how cognitive and motivational processes interact with each other. The hippocampus is involved in information processing and memory consolidation, which are influenced by subcortical neuromodulatory systems, including the median raphe nucleus (MnR) that regulates motivational and arousal states. Although accumulating evidence shows that the MnR influences hippocampal neural activity, it is not known whether and how the hippocampus influences neural activity of the MnR. In freely-behaving C57BL/6 mice, we simultaneously recorded neural activity of the hippocampus CA1 and MnR using multi-tetrode arrays. We found that the local field potential in the MnR exhibited bi-phasic activity: inhibition followed by excitation, immediately after the occurrence of hippocampal high-frequency (200Hz) ripple oscillation. The amplitude of the MnR bi-phasic activity was proportional to the amplitude of the hippocampal ripple oscillation. Moreover, electrical stimulation of the hippocampal CA1 elicited a similar rapid bi-phasic response in the MnR, confirming a hippocampal control of MnR activity. In addition, we found that 26% of the MnR neurons exhibited firing changes at the time of the occurrence of ripple oscillation. Their firing patterns can be classified into several types (type-1, 2, 3 and others). Importantly, changes in the firing rate of many neurons were correlated with changes in ripple-amplitude. Together, our results suggest that hippocampal neural activity closely influences that of the MnR during ripple events. In light of previous research showing that hippocampal ripples/sharp waves influence only limited forebrain regions, our data suggest that ripple events influence much larger brain regions than previously thought. Ripples generated within the hippocampus mainly occur during stand-by or non-aroused states, and are thought to play a crucial role in memory consolidation processes. We propose that hippocampal ripple oscillation influences large forebrain areas in information processing and memory consolidation by altering neural activity of the ascending raphe system.