Direct and indirect pathway neurons in the dorsal striatum bidirectionally modulate negative affect

Authors

• KH LeBlanc
• DM Friend
• KP Nguyen
• AV Kravitz

Abstract

Recent evidence demonstrates that stimulation of direct pathway medium spiny neurons (dMSNs) in the dorsal striatum is reinforcing, while stimulation of indirect medium spiny neurons (iMSNs) in the dorsal striatum is aversive. In addition, a number of disorders involving the striatal dopamine system, such as Parkinson’s disease, addiction, and obesity, are comorbid with anxiety and depression. Based on this evidence, we hypothesized that iMSNs and dMSNs may respond differentially to anxiety, and thus stimulating iMSNs may have anxiogenic effects while stimulating dMSNs may have anxiolytic effects. Using in vivo electrophysiology we found that the firing rate of a subset of MSNs in the dorsal striatum was substantially higher in either the open or closed arms of the elevated zero maze, suggesting that the firing of these neurons may be linked to anxiety state. Using optogenetic techniques, we have found that directly stimulating iMSNs in the dorsal striatum decreases the percent of time spent in the open arms of an elevated zero maze and time in the center of an open field, consistent with an anxiogenic-like effect. Conversely, stimulating dMSNs has the opposite effect, increasing the percent of time in the open arms and center time in the open field. Stimulating dMSNs also increased sucrose preference, a measure of anhedonia. Our results indicate a potential role of iMSNs and dMSNs in the striatum in affective states, which could have serious implications for a number of disorders, including Parkinson’s disease, OCD, addiction and obesity.

Scientific Focus Area: Neuroscience

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