Reward Maximization Assessed Using a Sequential Patch Depletion Task in a Large Sample of Heterogeneous Stock Rats.

Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water "patches" and could elect to "stay" in the current patch or "leave" for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. While differences in traditional DD measures (e.g., delay gradient) have been detected between males and females, these effects were small and inconsistent. However, when examining measures of reward maximization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. This pattern of choice resulted in males having a higher rate of reinforcement than females. Consistent with this, there was some evidence that females deviated from the optimal more, leading to less reward. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.

Reward maximization assessed using a sequential patch depletion task in a large sample of heterogeneous stock rats.

Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water "patches" and could elect to "stay" in the current patch or "leave" for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. Males and females did not significantly differ on traditional measures of DD (e.g. delay gradient; AUC). When examining measures of patch utilization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. Consistent with this, there was some evidence that females deviated from reward maximization more than males. However, when controlling for body weight, females had a higher normalized rate of reinforcement than males. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.

The huntingtin inclusion is a dynamic phase-separated compartment.

Inclusions of disordered protein are a characteristic feature of most neurodegenerative diseases, including Huntington's disease. Huntington's disease is caused by expansion of a polyglutamine tract in the huntingtin protein; mutant huntingtin protein (mHtt) is unstable and accumulates in large intracellular inclusions both in affected individuals and when expressed in eukaryotic cells. Using mHtt-GFP expressed in Saccharomyces cerevisiae, we find that mHtt-GFP inclusions are dynamic, mobile, gel-like structures that concentrate mHtt together with the disaggregase Hsp104. Although inclusions may associate with the vacuolar membrane, the association is reversible and we find that inclusions of mHtt in S. cerevisiae are not taken up by the vacuole or other organelles. Instead, a pulse-chase study using photoconverted mHtt-mEos2 revealed that mHtt is directly and continuously removed from the inclusion body. In addition to mobile inclusions, we also imaged and tracked the movements of small particles of mHtt-GFP and determine that they move randomly. These observations suggest that inclusions may grow through the collision and coalescence of small aggregative particles.