Steven F. Grieco
Nov 9, 2022; 42:8439-8449
Symposium and Mini-Symposium

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Sharon G. Kujawa
Nov 11, 2009; 29:14077-14085
BehavioralSystemsCognitive

Mahsa Altafi
Oct 23, 2024; 44:e0518242024-e0518242024
Systems/Circuits

Uri Hasson
Mar 5, 2008; 28:2539-2550
BehavioralSystemsCognitive

Yulia Lerner
Feb 23, 2011; 31:2906-2915
BehavioralSystemsCognitive

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

We recently demonstrated that transient attenuation of Toll-like receptor 4 (TLR4) in dorsal root ganglion (DRG) neurons, can both prevent and reverse pain associated with chemotherapy-induced peripheral neuropathy (CIPN), a severe side effect of cancer chemotherapy, for which treatment options are limited. Given the reduced efficacy of opioid analgesics to treat neuropathic, compared with inflammatory pain, the cross talk between nociceptor TLR4 and mu-opioid receptors (MORs), and that MOR and TLR4 agonists induce hyperalgesic priming (priming), which also occurs in CIPN, we determined, using male rats, whether (1) antisense knockdown of nociceptor MOR attenuates CIPN, (2) and attenuates the priming associated with CIPN, and (3) CIPN also produces opioid-induced hyperalgesia (OIH). We found that intrathecal MOR antisense prevents and reverses hyperalgesia induced by oxaliplatin and paclitaxel, two common clinical chemotherapy agents. Oxaliplatin-induced priming was also markedly attenuated by MOR antisense. Additionally, intradermal morphine, at a dose that does not affect nociceptive threshold in controls, exacerbates mechanical hyperalgesia (OIH) in rats with CIPN, suggesting the presence of OIH. This OIH associated with CIPN is inhibited by interventions that reverse Type II priming [the combination of an inhibitor of Src and mitogen-activated protein kinase (MAPK)], an MOR antagonist, as well as a TLR4 antagonist. Our findings support a role of nociceptor MOR in oxaliplatin-induced pain and priming. We propose that priming and OIH are central to the symptom burden in CIPN, contributing to its chronicity and the limited efficacy of opioid analgesics to treat neuropathic pain.

Neural circuits supporting innate behaviors, such as feeding, exploration, and social interaction, intermingle in the lateral hypothalamus (LH). Although previous studies have shown that individual LH neurons change their firing relative to the baseline during one or more behaviors, the firing rate dynamics of LH populations within behavioral episodes and the coordination of behavior-related LH populations remain largely unknown. Here, using unsupervised graph-based clustering of LH neurons firing rate dynamics in freely behaving male mice, we identified distinct populations of cells whose activity corresponds to feeding, specific times during feeding bouts, or other innate behaviors—social interaction and novel object exploration. Feeding-related cells fired together with a higher probability during slow and fast gamma oscillations (30–60 and 60–90 Hz) than during nonrhythmic epochs. In contrast, the cofiring of neurons signaling other behaviors than feeding was overall similar between slow gamma and nonrhythmic epochs but increased during fast gamma oscillations. These results reveal a neural organization of ethological hierarchies in the LH and point to behavior-specific motivational systems, the dysfunction of which may contribute to mental disorders.

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is downregulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration.

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in two male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin subunit B-Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B-Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76–98% of ganglion cells projecting to the superior colliculus were double labeled. Cells projecting to the superior colliculus constituted 4.0–6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by ~5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (I_h), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca²⁺-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I_h, and death, compromising audition at the young adult stage in HCN1^+/+, but not in HCN1^–/– genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca²⁺ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.

FAO Director-General José Graziano da Silva today praised UN Secretary-General Ban Ki Moon for his support in the fight against hunger at a meeting with FAO member countries, the Committee [...]

Representatives of all countries in Latin America and the Caribbean have gathered here this week to agree on the actions needed to definitively eradicate hunger in the region before 2025. [...]

Building on previous efforts, the Kingdom of Morocco will offer technical assistance to the Republic of Guinea through a South-South Cooperation Tripartite Agreement signed today at FAO headquarters by FAO [...]

A recent side event during the Council last week promoted South-South Cooperation (SSC) as a cost-effective means to addressing food insecurity, showcased FAO’s role as a facilitator and voiced the [...]

Santiago, Chile- The declaration of the XXI Specialized Meeting on Family Farming of MERCOSUR (REAF, in Spanish) held last week in Argentina, acknowledged the advances promoted by FAO’s Director General, [...]

FAO Director-General José Graziano da Silva will be away from Rome during the next few weeks. During this period he will be involved in a range of [...]

The [...]

FAO Director-General José Graziano da Silva today appointed Jacques Diouf as Special Envoy for the Horn of Africa and the Sahel.

In his new role, the former Director-General Jacques Diouf will [...]

FAO Director-General Graziano da Silva today opened the 150th session of the FAO Council, highlighting the successful conclusion of the Second International Conference on Nutrition (ICN2), held last month in [...]

5 December 2014, Rome – At the closure of the FAO Council held today, the [...]

Marrakesh, 15 December 2014 – African Ministers of Agriculture recognized the facilitating role of FAO “under the new strategic framework established with the leadership of the [...]

Berlin- FAO Director-General José Graziano da Silva has highlighted some of the most important events on the organization’s 2015 calendar during meetings with agriculture ministers who attended the Global Forum [...]

Just announced by the Group of Latin America and the Caribbean Countries (GRULAC)

The Group of Latin American and Caribbean Countries (GRULAC) of FAO in Rome is pleased to endorse the [...]

Rome - José Graziano da Silva, the [...]

Rome, The Africa Regional Group of Ambassadors and Permanent Representatives accredited  to the Rome based UN Agencies have announced the endorsement of the candidature of Dr. José Graziano da Silva [...]

Rome, 02 March 2015 - In a letter addressed to the Director-General, the Chairperson of the Near East Regional Group has announced their endorsement of the candidature [...]

In a letter addressed to the Director-General, the Ambassador of Malaysia to FAO, on behalf of the Chair of the Asia Group, has announced the endorsement of the [...]

South-South Cooperation is the mutual sharing and exchange of development solutions - knowledge, experiences and good practices, policies, technology and resources - between and among countries in the global [...]

FAO Director-General José Graziano da Silva has been selected as one of the world's most influential Latin Americans for his work against hunger and malnutrition in the world. In its [...]

Since the 1990s, rural transformations have helped millions of people exit poverty while remaining in rural areas. This underscores an important fact: revitalising rural economies helps create jobs for rural [...]

Addressing the plenary meeting in the closing session of the 159^th Session of the Council, the Director-General expressed his appreciation to delegates for their commitment and hard work to [...]

The Pre-Summit will bring together the global efforts to shape the transformation of agri-food systems.

Click here to access the presentation by QU Dongyu.

Information Note.

A statement by FAO Director-General QU Dongyu

Read the series on how FAO increased efficiency, effectiveness and transparency to better support its Members in the transformation of agrifood systems.

FAO member nations to choose head of the UN specialized agency in July during the 43rd session of the FAO Conference

The PSS Technical Cooperation Programme (TCP) team is excited to announce the launch of its newly designed webpages. The webpage has a fresh look [...]

Social protection and decent jobs are cornerstones of agrifood systems transformation, but they require strong political commitment

It depends on which variety of boomerang you're using. Our host Eric Schulze has more

In 1905, New York City hosted a grand procession for the last living soldier of a war that ended 90 years earlier

It's 1933 and Mae West is just arriving at Grauman's Chinese Theater for the premiere of I'm No Angel. It draws fans from all over the country—as well as an organized protest from conservative religious groups.

Two of the preeminent researchers of gene therapy hope to improve their patients' sight in an experimental operation (Stephen Voss/WPN)

ARTICLE: https://www.smithsonianmag.com/history/civil-war-veterans-come-alive-in-audio-and-video-recordings-97841665/ In this exclusive clip from the 1930s, Confederate veterans step up to the mic and let out their version of the fearsome rallying cry.

This is video of the new hermit crab species Pylopaguropsis mollymullerae taken by Ellen Muller at dive site 'Something Special', southern Caribbean. Credit: Rafael Lemaitre and Ellen Muller

The American Ingenuity Award winner on the connection between history and music

From gender roles to etiquette to fashion, step back in time to learn more about the real lives of the Regency women who inspired 'Bridgerton.' --- To read more about the Regency era - and 'Bridgerton' - check out these articles from Smithsonian Magazine: What 'Bridgerton' Gets Wrong About Corsets: https://www.smithsonianmag.com/history/what-bridgerton-gets-wrong-about-corsets-180976691/ The Real History Behind 'Queen Charlotte: A Bridgerton Story' https://www.smithsonianmag.com/smart-news/the-real-history-behind-queen-charlotte-a-bridgerton-story-180982130/ Digital Editorial Director: Brian Wolly Supervising Producer & Scriptwriter: Michelle Mehrtens Producer: Nicki Marko Video Editor: Sierra Theobald