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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

Second Time's a Charm? A Matched Case-Control Analysis of Revision Urethroplasty versus Primary Urethroplasty.

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Revision surgery can be a viable option for patients with stricture recurrence after urethroplasty. However, comparability of outcomes to a urethroplasty naïve population remains uncertain. The objective of this study is to assess outcomes of revision urethroplasty to a surgery naïve population using a matched case-control analysis.

Population structure and punctuated genomic hyper-diversity in Caenorhabditis briggsae.

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Comparative genomics provides a powerful framework to uncover the molecular and evolutionary mechanisms that shape genetic diversity, revealing how shared or lineage-specific processes influence their evolutionary trajectories. The nematode Caenorhabditis briggsae is distributed world-wide and is a comparative model to Caenorhabditis elegans in the biology of development, cellular mechanisms, neurobiology, complex trait mappings, and evolution. Following massive collection efforts by the nematode research community, we present the isolation of over 1,900 wild strains and analyses of genome sequences that catalog over six million single-nucleotide and insertion-deletion variants. These resources provide a powerful means to interrogate the causal genetic bases of phenotypic variation. Additionally, we describe C. briggsae population structure and discover new, genetically distinct groups within this primarily self-fertilizing species, including groups of highly related strains sampled across entire continents. We leverage expansive genetic variation to decipher the effects of linkage and selection on the distribution of genetic diversity across the genome and across geographic regions. Within the species, we find genomic regions with extremely high levels of genetic variation similar to hyper-divergent regions found in C. elegans and other species. These regions harbor new genes and variation enriched for environmental sensing and pathogen responses. Based on comparisons to the outbreeding sister species Caenorhabditis nigoni, we conclude that long-term balancing selection has maintained substantial functional variation, likely associated with ecological variation, within C. briggsae since its divergence from an outbreeding ancestor. Overall, this massive strain resource enables future comparative genetics studies, including genome-wide association study contrasts between Caenorhabditis species.

Two Clones, Two Paths: divergent intrinsic xylem traits and hydraulic responses to prolonged drought in poplar.

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Climate change is increasing the frequency and intensity of droughts, challenging the growth, hydraulic function and survival of woody plants. Poplar is a fast-growing species widely cultivated for biomass and cellulose production, but it is also highly sensitive to water deficit, with substantial variation among species and clones.
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