Inhibition of the dorsomedial striatal direct pathway is essential for the execution of action sequences.

Contrary to the previous notion that the dorsomedial striatum (DMS) is crucial for acquiring new learning, accumulated evidence has suggested that the DMS also plays a role in the execution of already learned action sequences. Here, we examined how the direct and indirect pathways in the DMS regulate action sequences using a task that requires animals to press a lever consecutively. Cell-type-specific bulk Ca2+ recording revealed that the direct pathway was inhibited at the time of sequence execution. The sequence-related response was blunted in trials where the sequential behaviors were disrupted. Optogenetic activation at the sequence start caused distraction of action sequences without affecting motor function or memory of the task structure. By contrast with the direct pathway, the indirect pathway was slightly activated at the start of the sequence, but the optogenetic suppression of such sequence-related signaling did not impact the behaviors. These results suggest that the inhibition of the DMS direct pathway promotes sequence execution potentially by suppressing the formation of a new association.

Factors Related to Job Continuance of Nurses Who Migrated to Japan: A Cross-Sectional Study.

Japan has accepted nurses from Indonesia, the Philippines, and Vietnam under the Economic Partnership Agreement, but nearly half of them have already left the workforce. This study aimed to clarify the factors related to the job continuance of nurses who migrated to Japan under the Economic Partnership Agreement. Our goal was to explore factors specific to migrant nurses and to contribute to the development of support measures for them. This research was a cross-sectional study in which a web-based questionnaire and interview were conducted at a single point in time. Migrant nurses (n = 40) participated in the web-based questionnaire survey. Of those, nine nurses were also interviewed. Spearman's rank correlation coefficient was used to establish correlations, and qualitative descriptive analysis was used to analyse interviews. The questionnaire survey results revealed the content of work, human relationships in the workplace, the number of night shifts, and satisfaction with the balance between work and private life were significantly and negatively correlated with the Intention to Quit scale total score. All correlation coefficients were less than 0.5, indicating weak correlations. Three categories emerged from the interviews as positive factors related to job continuance: "generous support from the workplace", "beneficial nursing experience in Japan", and "determination to live in Japan". A good working environment, generous support from the supervisor and colleagues, high values of nursing in Japan, and desire to migrate to Japan were the factors that had a positive effect on migrant nurses' job continuance in Japan. Understanding the characteristics of migrant nurses and providing generous support will enable them to continue working in Japan. This study was not registered.

Chronic social defeat stress impairs goal-directed behavior through dysregulation of ventral hippocampal activity in male mice.

Chronic stress is a risk factor for a variety of psychiatric disorders, including depression. Although impairments to motivated behavior are a major symptom of clinical depression, little is known about the circuit mechanisms through which stress impairs motivation. Furthermore, research in animal models for depression has focused on impairments to hedonic aspects of motivation, whereas patient studies suggest that impairments to appetitive, goal-directed motivation contribute significantly to motivational impairments in depression. Here, we characterized goal-directed motivation in repeated social defeat stress (R-SDS), a well-established mouse model for depression in male mice. R-SDS impaired the ability to sustain and complete goal-directed behavior in a food-seeking operant lever-press task. Furthermore, stress-exposed mice segregated into susceptible and resilient subpopulations. Interestingly, susceptibility to stress-induced motivational impairments was unrelated to stress-induced social withdrawal, another prominent effect of R-SDS in mouse models. Based on evidence that ventral hippocampus (vHP) modulates sustainment of goal-directed behavior, we monitored vHP activity during the task using fiber photometry. Successful task completion was associated with suppression of ventral hippocampal neural activity. This suppression was diminished after R-SDS in stress-susceptible but not stress-resilient mice. The serotonin selective reuptake inhibitor (SSRI) escitalopram and ketamine both normalized vHP activity during the task and restored motivated behavior. Furthermore, optogenetic vHP inhibition was sufficient to restore motivated behavior after stress. These results identify vHP hyperactivity as a circuit mechanism of stress-induced impairments to goal-directed behavior and a putative biomarker that is sensitive to antidepressant treatments and that differentiates susceptible and resilient individuals.

Opposing Ventral Striatal Medium Spiny Neuron Activities Shaped by Striatal Parvalbumin-Expressing Interneurons during Goal-Directed Behaviors.

Medium spiny neurons (MSNs) of mice show opposing activities upon the initiation of a food-seeking lever press task. Ventromedial striatal (VMS)-MSNs are inhibited but ventrolateral striatal (VLS)-MSNs are activated; these activities mediate action selection and action initiation, respectively. To understand what input shapes the opposing MSN activities, here, we monitor cortical input activities at the cell population level and artificially reverse them. We demonstrate that the ventral hippocampus (vHP) and the insular cortex (IC) are major inputs to the VMS and VLS, both projections show silencing at the trial start time, and the vHP-VMS and IC-VLS pathways form functionally coupled input-output units during the task. Of note, the upstream IC silencing is converted to the downstream VLS-MSN activation. We find biased localization of striatal parvalbumin-expressing interneurons (PV INs) and verify PV IN-dependent feedforward architecture in the VLS. Our results reveal a distinct mode of cortico-striatal signal conveyance via feedforward disinhibition in behaving animals.