It has long been recognized that the dorsal striatum is an essential brain region for control of action selection based on action–outcome contingency learning, particularly when the available actions are bound to rewarding outcomes. In principle, intertemporal choice in the delay‐discounting task—a validated measure of choice impulsivity—involves reward‐associated actions that require the recruitment of the dorsal striatum. Here, we conjecture about ways the dorsal striatum is involved in choice impulsivity. Based on a selective body of studies, we begin with a brief history of research on choice impulsivity and the dorsal striatum, and then provide a comprehensive summary of contemporary studies utilizing human neuroimaging and animal models to search for links between choice impulsivity and the dorsal striatum. In particular, we discuss in‐depth the converging evidence for the associations of choice impulsivity with the reward valuation coded by the caudate, a ventral‐to‐dorsal gradient in the dorsal striatum, the origins of striatal afferents, and developmental maturation of frontostriatal connectivity during adolescence.

Alzheimer disease is a neurodegenerative disease that constitutes the most common form of dementia without a cure. Alzheimer's Association Reports projected that the social and economic burden and the global prevalence of Alzheimer disease will grow constantly until 2050 [1], demanding immediate attention to research on the treatment and prevention of Alzheimer disease. The pathogenesis of Alzheimer disease is defined by the neurotoxic accumulation of extracellular amyloid-β plaques and intracellular tau neurofibrillary tangles, glial scarring and gliosis, and aberrant alterations in synaptic plasticity, ultimately resulting in severe cognitive impairments and extensive neuronal loss [2]. The cognitive dysfunctions observed in Alzheimer disease primarily consist of memory loss and problems in language or thinking skills. Among the diverse causes of Alzheimer disease identified to date, the foremost studies have revealed that Alzheimer disease

Objective Stimulant use instigates abstinence syndrome in humans. miRNAs are a critical component for the pathophysiology of stimulant abstinence. Here we sought to identify a miRNA marker of methamphetamine abstinence in the circulating extracellular vesicles (cEVs). Methods miR-137 in the cEVs was quantified by qPCR in thirty-seven patients under methamphetamine abstinence and thirty-five age-matched healthy controls recruited from 2014 to 2016 from the general adult population in a hospital setting, Seoul, South Korea. Diagnostic power was evaluated by area under curve in the receiver-operating characteristics curve and other multiple statistical parameters. Results Patients under methamphetamine abstinence exhibited a significant reduction in cEV miR-137. Overall, cEV miR-137 had high potential as a blood-based marker of methamphetamine abstinence. cEV miR-137 retained the diagnostic power irrespective of the duration of methamphetamine abstinence or methamphetamine use. Interestingly, cEV miR-137 interacted with age: Control participants displayed an aging-dependent reduction of cEV miR-137, while methamphetamine-abstinent patients showed an aging-dependent increase in cEV miR-137. Accordingly, cEV miR-137 had variable diagnostic power depending on age, in which cEV miR-137 more effectively discriminated methamphetamine abstinence in the younger population. Duration of methamphetamine use or abstinence, cigarette smoking status, depressive disorder, or antidepressant treatment did not interact with the methamphetamine abstinence-induced reduction of cEV miR-137. Conclusion Our data collectively demonstrated that miR-137 in the circulating extracellular vesicles held high potential as a stable and accurate diagnostic marker of methamphetamine abstinence syndrome.

Nicotine can diversely affect neural activity and motor learning in animals. However, the impact of chronic nicotine on striatal activity in vivo and motor learning at long‐term sparse timescale remains unknown. Here, we demonstrate that chronic nicotine persistently suppresses the activity of striatal fast‐spiking parvalbumin interneurons, which mediate nicotine‐induced deficit in sparse motor learning. Six weeks of longitudinal in vivo single‐unit recording revealed that mice show reduced activity of fast‐spiking interneurons in the dorsal striatum during chronic nicotine exposure and withdrawal. The reduced firing of fast‐spiking interneurons was accompanied by spike broadening, diminished striatal delta oscillation power, and reduced sample entropy in local field potential. In addition, chronic nicotine withdrawal impaired motor learning with a weekly sparse training regimen but did not affect general locomotion and anxiety‐like behavior. Lastly, the excitatory DREADD hM3Dq‐mediated activation of striatal fast‐spiking parvalbumin interneurons reversed the chronic nicotine withdrawal‐induced deficit in sparse motor learning. Taken together, we identified that chronic nicotine withdrawal impairs sparse motor learning via disruption of activity in striatal fast‐spiking parvalbumin interneurons. These findings suggest that sparse motor learning paradigm can reveal the subtle effect of nicotine withdrawal on motor function and that striatal fast‐spiking parvalbumin interneurons are a neural substrate of nicotine's effect on motor learning.

No abstract

Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects of acute subanesthetic ketamine treatment by bioinformatics analyses of miRNAs in the medial prefrontal cortex of male C57BL/6J mice. Gene Ontology and KEGG pathway analyses of the genes putatively targeted by ketamine-responsive prefrontal miRNAs revealed that acute subanesthetic ketamine modifies ubiquitin-mediated proteolysis. Validation analysis suggested that miR-148a-3p and miR-128-3p are the main players responsible for the subanesthetic ketamine-mediated alteration of ubiquitin-mediated proteolysis through varied regulation of ubiquitin ligases E2 and E3. Collectively, our data imply that the prefrontal miRNA-dependent modulation of ubiquitin-mediated proteolysis is at least partially involved in the mode of action by acute subanesthetic ketamine treatment.

No abstract

No abstract