Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca²⁺ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling.

SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.

SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.

Investment of cognitive effort is required in everyday life and has received ample attention in recent neurocognitive frameworks. The neural mechanism of effort investment is thought to be structured hierarchically, with dorsal anterior cingulate cortex (dACC) at the highest level, recruiting task-specific upstream areas. In the current fMRI study, we tested whether dACC is generally active when effort demand is high across tasks with different stimuli, and whether connectivity between dACC and task-specific areas is increased depending on the task requirements and effort level at hand. For that purpose, a perceptual detection task was administered that required male and female human participants to detect either a face or a house in a noisy image. Effort demand was manipulated by adding little (low effort) or much (high effort) noise to the images. Results showed a network of dACC, anterior insula (AI), and intraparietal sulcus (IPS) to be more active when effort demand was high, independent of the performed task (face or house detection). Importantly, effort demand modulated functional connectivity between dACC and face-responsive or house-responsive perceptual areas, depending on the task at hand. This shows that dACC, AI, and IPS constitute a general effort-responsive network and suggests that the neural implementation of cognitive effort involves dACC-initiated sensitization of task-relevant areas.

SIGNIFICANCE STATEMENT Although cognitive effort is generally perceived as aversive, its investment is inevitable when navigating an increasingly complex society. In this study, we demonstrate how the human brain tailors the implementation of effort to the requirements of the task at hand. We show increased effort-related activity in a network of brain areas consisting of dorsal anterior cingulate cortex (dACC), anterior insula, and intraparietal sulcus, independent of task specifics. Crucially, we also show that effort-induced functional connectivity between dACC and task-relevant areas tracks specific task demands. These results demonstrate how brain regions specialized to solve a task may be energized by dACC when effort demand is high.

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.

SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

Today leading international experts on climate change, the IPCC, presented their latest report on the impacts of climate change on humanity, and what we can do about it. It’s a lengthy report, so we’ve shrunk it down to Oxfam's five key takeaways on climate change and hunger. 1. Climate change: the impacts on crops are worse than we thought Climate change has [...]

Banana split, banana muffins, banana bread, banana pudding, banana pancakes – whether plain, cooked, baked or fried, bananas are among the most widely consumed fruits on the planet. However, how much do we really know about this most produced and exported fruit? Here are 11 interesting facts you should know about bananas: Based on written references discovered in Sanskrit around the year [...]

The 2019 Report of the Technical Cooperation Programme (TCP) examines the role of the TCP to deliver FAO technical assistance for agriculture, food and nutrition in response to countries’ most [...]

Perhaps it was not just a massive slice that made Pizza Rat a true New Yorker

The positive outcomes won’t be immediately apparent, but will help reduce the strain on our healthcare system

Tour world-class museums, read historic cookbooks, browse interactive maps and more

The bright blue pigment that adorns the Bust of Nefertiti’s crown can now be used to study molecular biology

Select Andrew Lloyd Webber productions will stream on YouTube for 48 hours at a time

The Archaeological Institute of America launched its Build Your Own Monument challenge early to inspire families quarantining at home

The opossum-sized mammal lived in Madagascar at the end of the age of the dinosaurs

The National Book Award winner's new book delves into matters of family grief and loss

A young white bear from Manitoba while lazily enjoying a soft snowfall. It is morning in Hudson Bay, Canada, and the bear has just woken up. I succeeded in capturing it at an extreme temperature (-26 °), in a surreal silence, after observing its habits for a few days. The polar bear spends most of its time sleeping and lounging in the snow. It only moves when it's hungry. To hunt its favorite prey - the seal - it is willing to walk hundreds of miles. Its refined nose allowes the bear to sneak up on its prey with a paw when the seal rises to the surface to breathe.

A museum director looks to the past to explain why 'Aloha' is as necessary as ever

The COVID-19 briefings started out as an urgent response to a public health crisis. As John Gushue writes, Premier Dwight Ball has grown comfortable in the role of hosting a program focused on government programs.

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

The following is a post by Kristi Finefield, Reference Specialist in the Prints & Photographs Division, and member of the Picture This blog team. Images have a way of opening our eyes to new aspects of a well-known story. When I think of singer Marian Anderson, an image of her performing at the Lincoln Memorial […]

It works like a very fine "molecular knob" able to modulate the electrical activity of the neurons of our cerebral cortex, crucial to the functioning of our brain.

A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen of the investigational antiviral remdesivir plus the anti-inflammatory drug baricitinib for coronavirus disease 2019 (COVID-19) has begun.

Graduation is on hold for Dalhousie University medical student Manveer Bal, so he's decided to spend his newfound free time volunteering at the epicentre of the COVID-19 outbreak in Nova Scotia.

The Best Museum Experience of All Things Washington, D.C. Experience the stories behind the people and events of the Nation's Capital.

Legal experts and leading scientists have teamed up with Creative Commons to create the Open COVID Pledge to help speed up the battle against the coronavirus pandemic. The Pledge gives broad permission to anyone to use intellectual property not otherwise accessible to the public, and generally replaces the need for any other license or royalty agreement.

The BIS Statistical Bulletin is published quarterly and summarises all BIS statistics in tabular form. It includes introductions to each data set and a glossary of statistical terms.

A fresh look at classical dance forms  Telegraph India

The Vancouver Whitecaps said it has ordered two player to self-quarantine for 14 days after they violated club and league orders to abide by physical distancing guidelines in B.C.

City of Kitchener bylaw enforcement says cooperation with physical distancing rules is weather-dependent, with more people getting out and about on sunny days. Wilfrid Laurier University professor Anne Wilson tells CBC Kitchener-Waterloo why some may be tempted to bend the rules as time goes by.

A Quebec-born Super Bowl champion is making the move from the offensive line to the medical front line.

Bryan Reid is known for building custom log homes on his HGTV reality show Timber Kings, and he’s also in the business of pulp — cedar pulp used to make medical garments,an effort critical during the COVID-19 pandemic.

Farmers markets throughout B.C.’s Interior and South Coast are ramping up for their spring seasons, but COVID-19 has forced them to make some changes to how they operate. 

From age 17, Ana Maria prayed to serve God in Switzerland. While she waited, she became a dance instructor with no idea dance would become her ministry.

The sport is considering radical rule changes as it tries to balance centuries of tradition with the modern need to move things along.

The COVID-19 pandemic may be keeping families physically distant, but that doesn't mean you can't show someone you care.

Hamilton Conservation Authority is re-opening the Hamilton-to-Branford Rail Trail, while the city announced the reopening of the Hamilton Waterfront Trail, between Confederation Park and the Burlington Lift Bridge.

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One of the main mechanisms of azole resistance of Aspergillus fumigatus is thought to be a reduction in the drug’s affinity for the target molecule, Cyp51A, due to its amino acid mutation(s). It is known that the azole resistance pattern is closely related to the mutation site(s) of the molecule. In this study, we tried to develop a simple and rapid detection method for cyp51A mutations using the endonuclease Surveyor nuclease. The Surveyor nuclease assay was verified using several azole-resistant strains of A. fumigatus that possess point mutations in Cyp51A. For validation of the Surveyor nuclease assay, blind tests were conducted using 48 strains of A. fumigatus (17 azole-resistant and 31 azole-susceptible strains). The Surveyor nuclease assay could rapidly detect cyp51A mutations with one primer set. Also, all the tested strains harboring different cyp51A single point mutations could be clearly distinguished from the wild type. The Surveyor nuclease assay is a simple method that can detect cyp51A mutations rapidly.