The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain.

SIGNIFICANCE STATEMENT We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin, and corticotropin-releasing hormone-expressing neurons in the CeA that project to the parabrachial nucleus. We show that this pathway regulates the activity of pain-related neurons in parabrachial nucleus, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief.

Stress alters brain function by modifying the structure and function of neurons and astrocytes. The fine processes of astrocytes are critical for the clearance of neurotransmitters during synaptic transmission. Thus, experience-dependent remodeling of glial processes is anticipated to alter the output of neural circuits. However, the molecular mechanisms that underlie glial structural plasticity are not known. Here we show that a single exposure of male and female mice to an acute stress produced a long-lasting retraction of the lateral processes of cerebellar Bergmann glial cells. These cells express the GluA1 subunit of AMPA-type glutamate receptors, and GluA1 knockdown is known to shorten the length of glial processes. We found that stress reduced the level of GluA1 protein and AMPA receptor-mediated currents in Bergmann glial cells, and these effects were absent in mice devoid of CPEB3, a protein that binds to GluA1 mRNA and regulates GluA1 protein synthesis. Administration of a β-adrenergic receptor blocker attenuated the reduction in GluA1, and deletion of adenylate cyclase 5 prevented GluA1 suppression. Therefore, stress suppresses GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway, and reduces the length of astrocyte lateral processes. Our results identify a novel mechanism for GluA1 subunit plasticity in non-neuronal cells and suggest a previously unappreciated role for AMPA receptors in stress-induced astrocytic remodeling.

SIGNIFICANCE STATEMENT Astrocytes play important roles in synaptic transmission by extending fine processes around synapses. In this study, we showed that a single exposure to an acute stress triggered a retraction of lateral/fine processes in mouse cerebellar astrocytes. These astrocytes express GluA1, a glutamate receptor subunit known to lengthen astrocyte processes. We showed that astrocytic structural changes are associated with a reduction of GluA1 protein levels. This requires activation of β-adrenergic receptors and is triggered by noradrenaline released during stress. We identified adenylyl cyclase 5, an enzyme that elevates cAMP levels, as a downstream effector and found that lowering GluA1 levels depends on CPEB3 proteins that bind to GluA1 mRNA. Therefore, stress regulates GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway in astrocytes and remodels their fine processes.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.

SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

FAO has begun field tests for a new approach to measuring hunger and food insecurity – part of a collaboration with polling specialists Gallup, Inc. The project – known as Voices of the Hungry – is based on a “food insecurity experience scale,” with annual data collected using eight interview questions about people’s experiences of food insecurity over the preceding [...]

Constituting only 5 percent of the world population, indigenous peoples nevertheless are vital stewards of the environment. Traditional indigenous territories encompass 22 percent of the world’s land surface, but 80 percent of the planet’s biodiversity.  A third of global forests, crucial for curbing gas emissions, are primarily managed by indigenous peoples, families, smallholders and local communities. Indigenous foods are also particularly [...]

Paseano Gómez López is a farmer from Nuevo Sonora, Chiapas state, Mexico. He grows corn and chili peppers. But to cultivate fields, farmers need money to buy supplies. They are often forced to take loans at high interest rates (10-20 percent). Sometimes, the farm’s yields don’t even cover the costs and they fall into debt. Farmers in Mexico are also battling with poor [...]

Disasters, like an earthquake or a violent coup d’état, can strike suddenly, or like droughts and floods, develop slowly. Emergencies are devastating for people everywhere, but for those whose livelihoods or food needs depend entirely on agriculture and natural resources, these disasters can often be overwhelming. FAO addresses emergencies in a variety of ways from early warning and preparedness to [...]

An independent survey finds that although NPS's annual budget is around $3 billion, Americans are willing to pay much more

Female dolphins, it seems, aren’t immune to the allure of a harmonizing boy band

Angry historians say the stretch of concrete was one of the largest remaining sections of the inner wall

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

The crustaceans' guts pulverize plastics into tiny bits that can be consumed by even smaller creatures at the base of the ocean food chain

Coyotes, bears and more are enjoying areas usually reserved for crowds of human visitors

Seventy-five years after a memorable mission, the B26 bomber 'Flak-Bait' undergoes preservation at the National Air and Space Museum

Highway 8, otherwise known as the Dempster Highway, will be closed to all traffic at 5 p.m. on Friday, according to the government of the Northwest Territories.

A woman who lost her sister to COVID-19 at the start of the month is thanking the staff at Northwood who took "excellent" care of her in her final days. Jean Harrigan, 90, is being remembered for her caring and lively nature.

Hope you didn't pack away those winter boots yet: southwestern Manitoba, from Riding Mountain south to the Canada-U.S. border, is expected to get heavy rain and snow Friday night.

Manitoba health officials says visits can be done via the internet, through window panes, or outside at a distance if everyone is healthy. People whose moms are in a hospital or a care home can still drop off gifts of food or clothing.

With the business world -- and the world at large, for that matter -- changing at what feels like a moment's notice, businesses and brands have never been required to be as limber as in this current moment. Marketing leaders want hard evidence and objective facts for decision making. It wasn't long ago that multi-touch attribution was the prized child of the hype cycle among marketers.

Oracle and Zoom just entered a deal that for once is more about technological audacity than about dollars -- a partnership to host Zoom on Oracle Cloud Infrastructure. In just a few months -- basically since the beginning of the novel coronavirus pandemic -- Zoom has seen demand for its service grow from about 10 million daily meeting participants to more than 300 million.

Toronto Mayor John Tory said Tuesday that there have been preliminary talks with Major League Baseball's Blue Jays and the NBA's Raptors about a return to action as restrictions from the COVID-19 pandemic begin to ease.

LACO AT HOME Features Sheku Kanneh-Mason Interview and Performance & More  Broadway World

More than a dozen First Nations in northeastern Ontario have closed their borders to outsiders during the pandemic. It's creating some friction, but in the long-run could help to better define what Indigenous self-government really means. 

Even though this year's food truck season is looking dicey, Tyler Schmidt says he's doing his best to find business where he can.

As a child, Fay Richardson wanted to dance, with the grace and movement of ballet captivating her. Now, at 79-years-old, she's doing just that.

We are connected to one another and to generations past and future.

Friends Derek and Josiah, who grew up in OM, talk about their most recent adventure: one year producing videos in the Middle East and North Africa.

Living on a 10-acre plot of land 100 kilometres outside Toronto, David Stevens thought he and his family were well prepared to ride out the COVID-19 quarantine. But after a call from his mother, he learned that even the best laid plans can go wrong.

The coronavirus pandemic has forced major professional sports leagues across North America to push the pause button. But even if the NHL, CFL, NBA or MLS are given the green light, many fans have reservations about returning to arenas until a vaccine for the virus is available.

Team Homan, Canada’s 2018 Olympic women’s curling team and the 2017 World Women’s Curling Champions have announced that the team has parted ways with lead Lisa Weagle. 

Team Homan's decision to part ways with Lisa Weagle dramatically changed the look of one of the country's top rinks and put the all-star lead at the top of curling's free agent list.

Many designers use golden ratio in their artworks as it can create organic and aesthetically pleasing composition. You can easily find examples in daily life such as shell, flower and logos. We can also use golden ratio in SOLIDWORKS. It

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A group of people open to the Holy Spirit's leading find an open door for ministry in Nazareth.

By utilising short-term teams and partnering with local churches, OM Israel realigns its field focus.

In an annual OM Guatemala outreach, volunteers are challenged to leave their comfort zone and share God’s love in a different way.

OM’s new Director in Hong Kong, Sonia Yip, shares why she’s passionate about seeing young people find their place in God’s kingdom.

Singapore :: A Frenchman makes friends with a community of foreign workers in Singapore.

It matters not if we are from 200 countries; we are one in Christ and shall be for eternity. OMNI-team member Greg Kernaghan about ‘globalisation’.

International short-term volunteers reach out to an elderly Jewish couple and share comfort from God's Word.

The iPhone offers a highly polished user experience, but iOS does have some quirks that you might find irritating. Our quick tips can help you shut down some of the biggest culprits.

Ingrid Newkirk isn’t sure exactly how many times she has been arrested. “Definitely a few dozen,” she’ll say, if you ask. I’ve just done exactly that, so right now the British-born founder of People for the Ethical Treatment of Animals (PETA) is running me through a sort of greatest hits of her law-baiting exploits and the jailtime they have brought her in the name of animal rights.

Thirteen participants in a weeklong outreach recently interacted with refugees, supporting OM’s refugee work in Linz.

IRAQ’S prime ministerial merry-go-round continues to spin apace. Spy chief Mustafa al-Kadhimi, director of the country’s National Intelligence Service, is now the third prime minister designate this year, following the withdrawal of the two previous prospective candidates.

MARC Mazoyer is getting ready for the week ahead. He’s made soup, and a loaf of bread, and roasted a chicken and he’s thinking about what he’ll do with the food over the next few days. Some of the chicken can go into a dahl, and maybe a risotto, and he might make some quesadillas with it too. And the leftovers can go into a caesar salad. This is how Marc keeps physically well. But it’s how he keeps mentally well too.

"The messages teens hear are 'Enjoy life: no commitment, keep your choices open and choose comfort'. Is this the consequence of their own choices or of the generation that raised them? Probably both," shares Ewout.