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INTRODUCTION: Natural rewards and addictive substances both act on the brain’s reward system, however it remains unclear whether they reinforce actions through the same mechanisms. AIM(S): Our goal was to compare the strategy employed by mice when choosing between two actions with variable chance to access alcohol or sweetened solution. METHOD(S): We have developed a novel method to assess behavioral strategy employed by mice when selecting between options associated with different probabilities of receiving a reward. A group of animals is implanted with radiofrequency chips and introduced to an IntelliCage, where their activity in cage corners is continuously recorded. After a period of adaptation, mice are offered accessto saccharin or alcohol solution in two opposite corners, with free access to water in the remaining corners. Initially, upon entering a rewarded cornerthere is a 90%chance that accessto saccharine or alcohol solution will be granted after 2 seconds. As the procedure progresses, the probability changes periodically between 90% and 30% and cycles through all possible combinations between the two rewarded corners. RESULTS: We tested choice between solutions 0.1% (w/v) saccharin, 4% (v/v) ethanol or a combination of them. In case of the sweetened water reward, the main factor affecting choice was time elapsed from last decision. The effect of the outcome of the previous choice was also significant, but overall smaller. In case of the alcohol solution, the effects of time and previous outcome were weaker, animals were more likely to repeat previous choice. We also observed that irrespective of strategy choices follow a specific time pattern, with majority occurring at discrete intervals. CONCLUSIONS: The type of reward strongly affected animals’ behavioral strategy. Probabilistic access to sweetened water was associated with high probability of switching between choices, while access to alcohol solution led to frequent repeating of the same choice. FINANCIAL SUPPORT: NCN Sonata Bis UMO-2012/07/E/ NZ3/01785 .
INTRODUCTION: Reinforcement learning causes an action that produced a satisfying effect in a particular situation to become more likely to occur again in that situation. The process is essential in adaptive behavior; however, actual choices often appear to diverge from what could be inferred from simple reinforcement learning. AIM(S): Here we investigate how the time intervals between actions affect the choices made. METHOD(S): Groups of C57BL6/J mice were housed in IntelliCages with access to water and chow ad libitum and were able to access bottles with a reward in the form of a saccharin solution (0.1% w/v), alcohol (4% w/v), or a mixture of the two. The probability of receiving a reward in two of the cage corners changed to 0.9 or 0.3 every 48 h over a period of ~33 days. RESULTS: We observed that, in most animals, the odds of repeating the choice of a corner were increased if that choice was previously rewarded. Interestingly, the time elapsed from the previous choice also increased the probability of repeating the choice, irrespective of the previous outcome. Behavioral data were fitted with a series of reinforcement learning models based on Q‑learning. We found that introducing an interval‑dependent adjustment allowed for better description of the observed behavior, and the size of the time effect differed depending on the type of reward offered. CONCLUSIONS: We find that, at longer time intervals, repeating the previous choice becomes more probable, irrespective of the previous outcome. Thus, at least in this specific case, time may make a past mistake more likely to be repeated.
INTRODUCTION: The hallmark symptoms of Parkinson’s disease (PD) are progressive motor impairments. Nevertheless, PD is also associated with altered executive function and other cognitive impairments. While treatments of PD provide at least temporary relief from the motor symptoms, the effects of L-DOPA on the cognitive impairments may provide mixed effects and require further investigation. AIM(S): Here we assess changes in gene expression in the prefrontal cortex (PFC) of rats with unilateral lesion of midbrain dopamine neurons. METHOD(S): Male Wistar Han rats were infused with 6‑hydroxydopamine (6‑OHDA, 8 µg/4 µl) into the left medial forebrain bundle. The experimental animals were treated i.p. with L‑DOPA (12.5 mg/kg) supplemented with benserazide hydrochloride (6.25 mg/kg) daily for 14 days. An hour after the last dose, the rats were killed, and the left and right PFC were isolated separately. Analysis of gene expression was performed by RNA‑seq (Illumina PE 150, 20M pair reads per sample). Reads were aligned to rn6 rat reference genome using hisat2 2.1.0. RESULTS: We identified 12,459 genes with FPKM > 1 after L‑DOPA treatment in both ipsi‑ and contralateral portions of the PFC of rats lesioned with 6‑OHDA. Two‑way ANOVA revealed 48 genes with differential expression profiles. The effect of treatment was the most pronounced, and included transcripts linked to activity-regulated expression in neurons and metabolism in the glia. Ontology analysis of the genes with altered expression indicated over-representation of terms associated with cytokine and glucocorticoid signalling. The involvement of altered glucocorticoid signalling induced by L-DOPA treatment was also confirmed by analysis of the promoter regions of the regulated genes. CONCLUSIONS: Unilateral lesions of dopamine neurons lead to enhanced sensitization of neurons in PFC to L‑DOPA action. We show that, to a large extent, these changes appear to bilaterally affect the molecular profile of PFC.
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