The cerebellum influences motor control through Purkinje target neurons, which transmit cerebellar output. Such output is required, for instance, for larval zebrafish to learn conditioned fictive swimming. The output cells, called eurydendroid neurons (ENs) in teleost fish, are inhibited by Purkinje cells and excited by parallel fibers. Here, we investigated the electrophysiological properties of glutamatergic ENs labeled by the transcription factor olig2. Action potential firing and synaptic responses were recorded in current clamp and voltage clamp from olig2⁺ neurons in immobilized larval zebrafish (before sexual differentiation) and were correlated with motor behavior by simultaneous recording of fictive swimming. In the absence of swimming, olig2⁺ ENs had basal firing rates near 8 spikes/s, and EPSCs and IPSCs were evident. Comparing Purkinje firing rates and eurydendroid IPSC rates indicated that 1-3 Purkinje cells converge onto each EN. Optogenetically suppressing Purkinje simple spikes, while preserving complex spikes, suggested that eurydendroid IPSC size depended on presynaptic spike duration rather than amplitude. During swimming, EPSC and IPSC rates increased. Total excitatory and inhibitory currents during sensory-evoked swimming were both more than double those during spontaneous swimming. During both spontaneous and sensory-evoked swimming, the total inhibitory current was more than threefold larger than the excitatory current. Firing rates of ENs nevertheless increased, suggesting that the relative timing of IPSCs and EPSCs may permit excitation to drive additional eurydendroid spikes. The data indicate that olig2⁺ cells are ENs whose activity is modulated with locomotion, suiting them to participate in sensorimotor integration associated with cerebellum-dependent learning.

SIGNIFICANCE STATEMENT The cerebellum contributes to movements through signals generated by cerebellar output neurons, called eurydendroid neurons (ENs) in fish (cerebellar nuclei in mammals). ENs receive sensory and motor signals from excitatory parallel fibers and inhibitory Purkinje cells. Here, we report electrophysiological recordings from ENs of larval zebrafish that directly illustrate how synaptic inhibition and excitation are integrated by cerebellar output neurons in association with motor behavior. The results demonstrate that inhibitory and excitatory drive both increase during fictive swimming, but inhibition greatly exceeds excitation. Firing rates nevertheless increase, providing evidence that synaptic integration promotes cerebellar output during locomotion. The data offer a basis for comparing aspects of cerebellar coding that are conserved and that diverge across vertebrates.

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.

To determine whether Cav1.2 voltage-gated Ca²⁺ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca²⁺ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca²⁺ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca²⁺ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.

SIGNIFICANCE STATEMENT Reducing voltage-gated Ca²⁺ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination.

Feeding the world’s growing population, which is expected to go beyond 9 billion by 2050, is one of the world’s biggest challenges. Some of the highest rates of population growth are predicted to occur in areas that are highly dependent on the agriculture sector (i.e. crops, livestock, forests and fisheries). Sustainable agricultural growth is one of the most effective means [...]

Mountains provide freshwater and biodiversity, and are a major source of food. By definition, they dominate their surroundings with towering height and protect valleys and their inhabitants. They play a critical part in moving the world towards sustainable economic growth and have a leading role as indicators of climate change. As we celebrate the International Mountain Day, see how much you [...]

Every year, FAO publishes a number of major ‘State of the World’ reports containing balanced, science-based reviews of issues related to food, agriculture, forestry, fisheries and natural resources. The reports also cover vital areas such as food production and hunger alleviation, which are at the heart of FAO’s work. With close to 800 million people currently chronically undernourished and an extra [...]

The National Cherry Blossom Festival has moved online due to the novel coronavirus pandemic

Many teens have taken on the role, but not every Robin was a "boy" wonder

The exact molecule behind the Minamata mercury disaster, caused by a chemical plant’s wastewater, remains a point of disagreement

The Internet Archive describes the downloadable collection of more than one million books as a library, but critics call it piracy

Sourdough librarian Karl De Smedt has traveled the world to gather more than 120 jars of starters

The story behind the image, and its removal, led to mixed reactions from the public, including native communities

The rankings stay much the same from year to year, but in 2019, Pembroke Welsh corgis broke the top ten for the first time

This Sunday, celebrate the moms of the animal kingdom with kittens, polar bear cubs, eaglets and more

These paintings, sculptures and illustrations honor the bonds of motherhood

It all began when three frustrated women sought the no-bounce zone

In the early 20th century, Native people responded to the proclamation of Mother’s Day with powwows, ceremonies, rodeos, feasts, and songs

Henny Sundig is a pivotal figure in the history of WWII Danish resistance. In 1943, aged just 19, she risked it all to make a daring journey in her boat, Gerda III, to rescue as many Jews as she could.

Just across town from the Library of Congress in Washington, D.C., stands Gallaudet University, an institute for higher learning for the deaf and hard-of-hearing. In 1864, President Abraham Lincoln signed the law that allowed the school to begin issuing college degrees, a milestone for deaf people seeking higher education. Edward M. Gallaudet (right) was the […]

The following is a guest post by Katherine Blood, Curator of Fine Prints, Prints & Photographs Division. As the Library of Congress marks its 220th year of serving the nation, the publication of a new guide tells two stories: how staff have for decades worked with art professionals to build the collections and how by […]

The Bradford assay is a quick and fairly sensitive method for measuring the concentrations of proteins. It is based on the shift in absorbance maximum of Coomassie Brilliant Blue G-250 dye from 465 to 595 nm following binding to denatured proteins in solution.

Even celebrity chef Julia Child said that the sleek appliance made mixing 'marvelous'

A protein shredder that occurs in cell membranes of brain cells apparently also indirectly regulates the fat metabolism.

The Korean baseball league opens its delayed season Tuesday in empty stadiums across South Korea and Canada's Jamie Romak, along with the rest of the league's players, are getting used to a new baseball normal that includes rules against high fives and spitting, daily temperature checks and the absence of fans.

Eight COVID-19 cases are now connected to that workplace, including six employees.

Vincent Novara, Head of the Music Division's Acquisitions & Processing Section, describes his section's new teleworking practices during a global pandemic.

Jharkhand bans 11 brands of pan masala for one year to protect public health  Zee NewsJharkhand bans 11 pan-masala brands on health concerns  Hindustan TimesJharkhand Bans 11 Pan Masala Brands for One Year to Protect Public Health&n...

Visions 2020: Nydia Han and 6abc celebrates Asian Pacific American Heritage Month - 6abc  WPVI-TV

How Do American Indians Celebrate Mother's Day? | Smithsonian Voices | National Museum of the American Indian  Smithsonian.com

Netizens celebrate as Kamal Haasan crosses 6 million mark on Twitter  DNA India

On this week's edition of Olympic Games Replay, CBC Sports showcases some of the big moments from Canada's journey through the women's soccer tournament at the Rio Olympics.

Friends and family of Brady Francis, a 22-year-old man who died in 2018 after a hit-and-run collision, are proposing changes to make reporting vehicle collisions with wildlife mandatory in New Brunswick.

Four-time All Pro tight end Rob Gronkowski has agreed to a reunion with Tom Brady. The trade, finalized Tuesday night, brings Gronkowski and a seventh-round pick to Tampa Bay in exchange for a fourth-round selection.

Calgary Flames general manager Brad Treliving will watch Thursday's remote NFL draft and is planning to focus on how his football counterparts deal with the realities of their world during the COVID-19 pandemic.

Mayor Jane Castor has issued a letter of apology after Tampa didn't exactly give the best of welcomes to one of its newest and most famous residents when NFL superstar Tom Brady was ejected from a downtown park while working out.

New England head coach Bill Belichick said not taking a quarterback in the Patriots' first post-Tom Brady draft "wasn't by design."

There's a wonderfully quirky — and little known — information archive in downtown Winnipeg that predates Google and probably has more hidden secrets than the search engine giant.

Hope for a 2020 Grey Cup in Regina is slowly dwindling as the CFL hints at a season cancellation. 

OM SportsLink in Brazil hosts 85 children from a slum in São José dos Campos at their futsal school. They are amazed by open doors.

A third person was rescued off the roof of the burning building after the house went up in flames at about 11 p.m. on Thursday.

Deforestation in Brazil's Amazon rainforest rose sharply in April, government data showed on Friday, as the coronavirus outbreak keeps many environmental enforcers out of the field and the country prepares to deploy troops to fight illegal logging.

As British Columbians maintain physical distancing recommendations during the COVID-19 pandemic, this year’s Easter celebrations will have to change. In Kamloops, B.C., organizations are working to make sure Easter is as fun and social as it can be. 

It wasn’t all that long ago Brad Gushue wondered if he’d ever be a Brier champion after 13 appearances without ever hoisting the historic Tankard trophy. Times have changed in a hurry. Gushue is now a three-time Brier champion.

Two additional men have been charged with first-degree murder in the death of a 17-year-old Brampton boy shot and killed on New Year's Eve.

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

The post SOLIDWORKS Certification Celebrates 400,000! appeared first on SOLIDWORKS Education Blog.

Here’s what we should be expecting in the war on Covid-19.

Denver Newsroom, May 7, 2020 / 03:48 pm (CNA).- For the first time in over a century, the annual May 13 celebrations at the Fatima shrine will take place without the physical presence of pilgrims, the bishop of Fatima confirmed this week.

Cardinal Antonio Marto said in a May 3 statement that the celebrations for the Feast of Our Lady of Fatima “will take place as was announced April 6, without the physical presence of pilgrims, in the name of prudence to avoid the risk of spreading the novel coronavirus.”

“As planned in conjunction with the civil authorities, the May 12 and 13 celebrations for this year cannot have the physical presence of the pilgrims and will be transmitted by broadcast and digital media,” he continued.

The cardinal explained that hosting “an unpredictable multitude of people” gathering at a time when the coronavirus pandemic is still a serious threat would go against the efforts of health authorities to gradually lift restrictions imposed to slow the spread of the virus.

“We therefore respect, in an attitude of collaboration with the competent civil authorities, the guidelines for these celebrations to be held with a symbolic presence of participants,” Marto said.

The clarification over the Fatima feast day came as the Portuguese government gradually begins to ease restrictions that had been put in place in response to the pandemic, prompting speculation over whether the May 13 celebrations would be able to take place as normal. The annual event typically draws hundreds of thousands from around the world to the shrine.

The Portuguese Bishops’ Conference had announced earlier this month that public Masses could tentatively resume the weekend of Pentecost, May 30-31, in accordance with guidelines to be established by the country’s health department and the Catholic Church.

Cardinal Marto stressed that the decision to suspend public religious celebrations was based in a sense of responsibility toward the public health, as a way of loving one’s neighbor.

“[A]s much as our hearts would like to be in Fatima celebrating together in the same place, as has been the case since 1917, prudence counsels us not to do so this time,” he said, adding that Catholics can look forward to an end to the pandemic and an opportunity to gather together joyfully in the future.

Fr. Carlos Cabecinhas, rector of the Shrine of Our Lady of Fatima, encouraged pilgrims who are unable to physically attend the events to make an interior pilgrimage, participating in the events of the Solemnity of Our Lady of Fatima through the internet or social media.

“This is a painful time: the shrine exists to welcome the pilgrims and we cannot do so, this is a cause for great sadness; but this decision is also an act of responsibility toward the pilgrims, protecting their health and welfare,” the priest said.

The shrine’s website offers four steps to guide people on this interior pilgrimage.

According to the website, “the celebrations of May 12 and 13 will maintain the usual schedule with recitation of the Rosary at 9:30 p.m. followed by the Candlelight Procession. On the 13th the Rosary will be prayed at 9:00 a.m. followed by the International Mass and the Farewell Procession.”

In March, 24 countries were consecrated to the Sacred Heart of Jesus and the Immaculate Heart of Mary at the Shrine of Our Lady of Fatima.

At that ceremony, Cardinal Marto recalled that Saints Francisco and Jacinto Marto, shepherd children to whom an angel, and then the Blessed Virgin Mary appeared in 1916 and 1917 at Fatima, both died amid the victims of the Spanish flu pandemic.

To date, Johns Hopkins University has reported 26,182 cases of novel coronavirus in Portugal, with 1089 deaths.