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Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons.

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Striatal dopamine plays key roles in our normal and pathological goal-directed actions. To understand dopamine function, much attention has focused on how midbrain dopamine neurons modulate their firing patterns. However, we identify a presynaptic mechanism that triggers dopamine release directly, bypassing activity in dopamine neurons. We paired electrophysiological recordings of striatal channelrhodopsin2-expressing cholinergic interneurons with simultaneous detection of dopamine release at carbon-fiber microelectrodes in striatal slices. We reveal that activation of cholinergic interneurons by light flashes that cause only single action potentials in neurons from a small population triggers dopamine release via activation of nicotinic receptors on dopamine axons. This event overrides ascending activity from dopamine neurons and, furthermore, is reproduced by activating ChR2-expressing thalamostriatal inputs, which synchronize cholinergic interneurons in vivo. These findings indicate that synchronized activity in cholinergic interneurons directly generates striatal dopamine signals whose functions will extend beyond those encoded by dopamine neuron activity.

A feud that wasn't: acetylcholine evokes dopamine release in the striatum.

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In this issue of Neuron, Threlfell et al. (2012) report that synchronous activation of cholinergic interneurons evokes striatal dopamine release by activating presynaptic nicotinic acetylcholine receptors. These findings call for a fundamental reevaluation of the long-standing view that dopamine and acetylcholine "feud" over control of striatal circuitry.

Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task.

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The present investigation had two aims: (1) to study responses of dopamine neurons to stimuli with attentional and motivational significance during several steps of learning a behavioral task, and (2) to study the activity of dopamine neurons during the performance of cognitive tasks known to be impaired after lesions of these neurons. Monkeys that had previously learned a simple reaction time task were trained to perform a spatial delayed response task via two intermediate tasks. During the learning of each new task, a total of 25% of 76 dopamine neurons showed phasic responses to the delivery of primary liquid reward, whereas only 9% of 163 neurons responded to this event once task performance was established. This produced an average population response during but not after learning of each task. Reward responses during learning were significantly more numerous and pronounced in area A10, as compared to areas A8 and A9. Dopamine neurons also showed phasic responses to the two conditioned stimuli. These were the instruction cue, which was the first stimulus in each trial and indicated the target of the upcoming arm movement (58% of 76 neurons during and 44% of 163 neurons after learning), and the trigger stimulus, which was a conditioned incentive stimulus predicting reward and eliciting a saccadic eye movement and an arm reaching movement (38% of neurons during and 40% after learning). None of the dopamine neurons showed sustained activity in the delay between the instruction and trigger stimuli that would resemble the activity of neurons in dopamine terminal areas, such as the striatum and frontal cortex. Thus, dopamine neurons respond phasically to alerting external stimuli with behavioral significance whose detection is crucial for learning and performing delayed response tasks. The lack of sustained activity suggests that dopamine neurons do not encode representational processes, such as working memory, expectation of external stimuli or reward, or preparation of movement. Rather, dopamine neurons are involved with transient changes of impulse activity in basic attentional and motivational processes underlying learning and cognitive behavior.
Latest Updated Curations

Basal Ganglia Advances

 
 
Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Progress in Voltage Imaging

 
 
Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Navigation & Localization

 
 
Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.
Most Popular Recent Articles

Skin microbiota of fallow deer: Composition, diversity, and influencing factors.

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Understanding the microbiota of wild animals can contribute to the monitoring of population health or habitat changes. The skin microbiota of fallow deer remains poorly characterized and represents a gap in current veterinary microbiology research. The aim of this study was to analyse skin microbiota of fifteen clinically healthy fallow deer using next-generation sequencing. Genomic DNA was extracted from superficial skin swabs collected from three anatomical sites per individual (n = 45 samples) and sequenced targeting the V3-V4 region of the bacterial 16S rRNA gene using Illumina sequencing. The skin microbiota of fallow deer was highly diverse, with a broad range of bacterial taxa detected across samples. The most abundant genus was Sphingomonas, followed by Enhydrobacter, Chryseobacterium, Corynebacterium, Pseudomonas, Flavobacterium, Sporosarcina, and Staphylococcus. Significant differences in alpha diversity were detected between male and female fallow deer. Beta diversity analysis revealed significant differences in community composition according to sex and age, whereas no significant differences were observed among sampling locations or skin sites. To our knowledge, this is the first study to describe the skin microbiota composition of fallow deer, providing baseline data for future comparative and ecological microbiota studies in wild ruminants.

Comparing safety and efficacy of primary single anastomosis duodeno-ileal bypass vs. one anastomosis gastric bypass: 6 months analysis of MBSAQIP database.

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One-anastomosis gastric bypass (OAGB) and single-anastomosis duodenoileal bypass (SADI) are increasingly performed hypoabsorptive bariatric procedures, yet large-scale comparative data remain limited. This study compared 30-day and 6-month outcomes between primary OAGB and SADI using a national bariatric registry.

Optimized Amoxicillin Dosing is Associated with Higher Helicobacter pylori Eradication in Metabolic and Bariatric Surgery Candidates: A Retrospective Cohort Study.

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Patients with obesity are frequently underrepresented in Helicobacter pylori (H pylori) trials. In this population, physiological alterations including increased volume of distribution of hydrophilic antibiotics such as amoxicillin may result in subtherapeutic mucosal concentrations with standard fixed doses, contributing to suboptimal eradication rates in Metabolic and Bariatric Surgery (MBS) candidates. We evaluated the effectiveness and safety of a weight-adjusted amoxicillin regimen for improving H. pylori eradication in patients with obesity scheduled for MBS.
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