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.

Mass spectrometry-based sequencing of therapeutic oligonucleotides requires controlled fragmentation, but the effects of nucleotide composition, charge state, and chemical modification on collision-induced dissociation are not fully understood. This study systematically evaluates how these parameters influence precursor survival, base loss, and backbone fragmentation to improve and understand analytical characterization and fragmentation behavior of modified oligonucleotides.

Direct analysis in real time (DART) is an open-air ion source that does not require a sample preparation step. Only a few studies have focused on the negative-ion formation processes for low-polarity molecules. In this study, an ω-iodo oligo (vinylidene fluoride) telomer of known composition was investigated to elucidate the involved DART ionization mechanisms.

Migraine is a debilitating neurological disorder characterized by headaches, autonomic changes, and heightened sensitivity to stimuli. Traditional Chinese medicine, particularly the Chuanxiong-Baizhi (CX-BZ) herb pair, has shown clinical efficacy in migraine management, but its underlying mechanisms remain unclear.