Correlates of motivation and reward

Ikemoto, Satoshi

Abstract

Previous work done in our group has indicated that excitation of the septum may drive aspects of motivated behavior. To investigate, we injected a virus encoding channelrhodopsin-2 into the septum of wild-type mice, and a Cre-dependent virus into the septum of VGLUT2- and VGAT-Cre transgenic mice. We found that mice will lever-press to deliver ubiquitous photostimulation to septal neurons, as well as photostimulation exclusively to the glutamate but not GABA subpopulations. Because glutamate neurons in the septum are largely localized to the medial portion, we used fiber photometry to record aggregate activity from this neuron population and correlate it to behaviors during a natural reward-seeking task. After injecting a virus encoding the calcium indicator GCaMP6s and implanting a multimodal fiber into the medial septum of VGLUT2-Cre transgenic mice, we water-restricted the mice and trained them to press a lever that resulted in administration of sucrose from a port. Once the lever-pressing stabilized across days, indicating the mice had learned the behavior, we began photometry recordings. Preliminary results show that activity of the medial septum glutamate neurons did not change after the lever was introduced into the chamber, but decreased after lever-pressing, decreased even more after retrieving sucrose, and then increased after the bout of sucrose consumption ended. These data are consistent with the notion that septum glutamate neurons play a role in behavior-environmental interaction and their activity decreases as the behavioral sequence with respect to reward ends.