Elucidating the role of medial septum glutamate neurons in reward-seeking behaviors

Authors

• MD Marks
• S Ramos-Macial
• N Westcott
• AJ Kesner

Abstract

A hallmark of many psychiatric illnesses, including substance use disorders, is maladaptation in reward seeking. One of the first brain regions implicated in reward via electrical self-stimulation in rats is the Medial Septum (MS). The MS is known to be involved in navigation, learning, and theta rhythmicity in the hippocampus. However, recent studies found that optogenetic excitation of MS glutamate neurons (MSGLU) is reinforcing while another study found that general excitation of the MS enhances strategy switching in rats, a form of cognitive flexibility. How MSGLU neuronal activity correlates to reward seeking behaviors remains unknown. Therefore, chemogenetics, both excitatory and inhibitory, and fiber photometry were used to probe and visualize MSGLU activity during reward seeking paradigms in mice including the operant behaviors: fixed ratio 1 (FR1), progressive ratio (PR), and lever reversal. Inhibiting MSGLU activity seemed to decrease reward seeking during FR1 as well as increase consumption of the reward. However, enhancing MSGLU activity tended to enhance PR breakpoint ass well as improve reversal learning. Fiber photometry showed decreases in MSGLU signaling during reward consumption and lever pressing. MSGLU activity appears to track aspects of goal-related information and stimuli. While there is still more to learn about MSGLU signaling during reward seeking, these neurons as well as other neurons within the MS may be a therapeutic target for substance abuse and other psychiatric illnesses.

Scientific Focus Area: ACI/IRS

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