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.

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.

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.

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.

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

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

Vancomycin is a glycopeptide antibiotic used to treat severe Gram-positive infections; its narrow therapeutic window makes therapeutic drug monitoring (TDM) critical. We report the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure (RMP) to quantify vancomycin in human plasma and serum.

Acute pain in hospitalised patients is common, yet African data are scarce. We conducted a prospective point-prevalence study of hospitalised adult patients across Africa to determine acute pain prevalence and severity and investigate associations of pain with critical illness and 7-day mortality. On a single day, investigators assessed patients' worst pain in the preceding 24 hours using a 0 to 10 visual-numerical scale and recorded vital signs. Critical illness was defined as ≥1 vital sign out of range, in line with an international consensus definition. In-hospital mortality was assessed at day 7. Data are presented as median [interquartile range], n (%), and odds ratios with 95% confidence intervals. Between September and December 2023, 19,438 patients from 180 hospitals in 22 African nations were included (age 40 [29; 59] years; 10,874 [56%] female). Pain prevalence [95% CI] was 67.9% [67.9-68.5], with 2795 (14.4%) patients reporting severe pain (≥7/10). Pain was more common among patients admitted for emergency or trauma care and in surgical and high-care wards. Pain severity did not differ meaningfully between sexes. There was no evidence of an association between pain severity and critical illness; however, increasing pain severity was associated with a higher likelihood of 7-day mortality. These findings are comparable to data from high-income countries despite substantial differences in healthcare resources, suggesting that acute pain remains a persistent and underaddressed problem globally. This study provides the first large-scale evidence of acute pain burden in African hospitals and lays a foundation for future research aimed at comprehensively characterising in-hospital pain.

Mental health and substance use can coexist and worsen outcomes for youth. The goals of the Transformative and Evidence-based Approaches to Mental Health and Substance Use Screening (TEAMSS) quality improvement virtual learning collaborative were to enhance the implementation of screening and follow-up practices for adolescent substance use and mental health issues in primary care.