The Regulation of Effort Exertion by the Nucleus Accumbens Core

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2023

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Abstract

The nucleus accumbens core is believed to play an important role in regulating effort exertion. Effort can be explained as the energetic costs of an action relative to its long-term benefits. Using fixed-ratio schedules of reinforcement, different effort requirements can be imposed upon mice, as the cost per benefit is determined by these press-per-pellet ratios. Fixed-ratio schedules have long been used to study effort, and manipulations that impact more effortful behaviors to a greater extent have consistently been interpreted as demonstrating a decrease in the willingness to exert effort. For decades, in numerous studies, these effects have been consistently observed following manipulations that disrupt a specific region of the brain, the nucleus accumbens. In the accumbens there are two main types of neurons, the direct and indirect pathway neurons, that play different roles in behavior and project to different downstream structures. The accumbens has also traditionally been divided into two subregions, the core and the shell. Much of what is known about these circuits comes from work where the researchers inject drugs into the accumbens, but newer research methods have become far more precise. Optogenetic techniques, with improved temporal resolution, spatial resolution, and cell-type specificity, have become extremely useful tools across many areas of neurobiology; but optogenetics has yet to be applied specifically to questions regarding the regulation of effort. Here these questions have been addressed by combining optogenetics (activation or inhibition of direct or indirect pathway neurons in the core or shell) with various fixed-ratio procedures used to enforce distinct effort requirements. Pressing reductions elicited by activation of direct pathway neurons in the core were significant, but demonstrated no relationship with effort requirement. In contrast, effort-dependent pressing reductions were caused by activation of core indirect pathway neurons. Furthermore, this indirect effect was not caused by motor impairments or differences in appetite, because port-entry rates were maintained during these same sessions, regardless of ratio schedule. Although the direct pathway effect was effort-independent, activating these neurons in the core was also found to elicit persistent gnawing, upon inedible objects in the animals’ surroundings. In addition, significant increases in pressing were caused by inhibition of indirect pathway neurons in the core, and solely for the high-effort sessions. Lastly, optogenetic activation of indirect pathway neurons was found to elicit no behavioral effect when administered in the shell. These findings suggest that the willingness of animals to exert effort is being determined by the output of the indirect pathway projections from the core; and that these cells play this role somewhat exclusively, as the direct pathway is not regulating effort, and neither is the shell. But, indirect pathway neurons in the core determine willingness to exert effort on a moment-to-moment timescale, and this effort regulation process is bidirectional in nature, as demonstrated via bidirectional optogenetics. High output in these cells reduces the willingness to exert effort, whereas low output is associated with a greater willingness. These findings are novel, particularly the timescale of this effect, but in general they are in agreement with a large body of previous work. They also suggest that the two pathways and the two accumbal subregions play distinct roles in motivated behavior, and interestingly, core direct pathway activation can cause gnawing.

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Shoemaker, Charles Tyler (2023). The Regulation of Effort Exertion by the Nucleus Accumbens Core. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/27711.

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