Fabrizio Benedetti
Nov 9, 2005; 25:10390-10402
Symposia and Mini-Symposia

Nancy Kanwisher
Jun 1, 1997; 17:4302-4311
Articles

Nancy Kanwisher
Jun 1, 1997; 17:4302-4311
Articles

French translation of Press Release about BIS General Manager Agustín Carstens giving a speech on "Money in the digital age: what role for central banks?" (6 February 2018)

Microsoft has introduced a slew of new products, including the Surface Go 2, the Surface Book 3, Surface Headphones 2 and Surface Earbuds. Both the Surface Go 2 and the Surface Book 3 come in consumer and corporate versions. "The two products are very different," noted Rob Enderle, principal analyst at the Enderle Group. "The Go 2 is a high-value product -- the Surface Book 3 high innovation."

The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations.

SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning.

Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function.

SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function.

The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with l-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single-unit recordings and dendritic spine analyses on striatal medium spiny neurons (MSNs) in drug-naïve rAAV-injected male parkinsonian rats. rAAV-GFP injected LID-resistant hemi-parkinsonian Lewis rats displayed mild LID and no induction of striatal Nurr1 despite receiving a high dose of l-DOPA. However, Lewis rats overexpressing Nurr1 developed severe LID. Nurr1 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in l-DOPA-naïve rats striatal rAAV-Nurr1 overexpression (1) increased cortically-evoked firing in a subpopulation of identified striatonigral MSNs, and (2) altered spine density and thin-spine morphology on striatal MSNs; both phenomena mimicking changes seen in dyskinetic rats. Finally, we provide postmortem evidence of Nurr1 expression in striatal neurons of l-DOPA-treated PD patients. Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.

SIGNIFICANCE STATEMENT The transcription factor Nurr1 is ectopically induced in striatal neurons of rats exhibiting levodopa-induced dyskinesia [LID; a side-effect to dopamine replacement strategies in Parkinson's disease (PD)]. Here we asked whether Nurr1 is causing LID. Indeed, rAAV-mediated expression of Nurr1 in striatal neurons was sufficient to overcome LID-resistance, and Nurr1 agonism exacerbated LID severity in dyskinetic rats. Moreover, we found that expression of Nurr1 in l-DOPA naïve hemi-parkinsonian rats resulted in the formation of morphologic and electrophysiological signatures of maladaptive neuronal plasticity; a phenomenon associated with LID. Finally, we determined that ectopic Nurr1 expression can be found in the putamen of l-DOPA-treated PD patients. These data suggest that striatal Nurr1 is an important mediator of the formation of LID.

It’s been around for thousands of years; the UN General Assembly named an international year for it in 2013; and now it has been sent into space. Quinoa is a superfood in more ways than one. It is a good source of protein, the highest of all the whole grains; and its edible seeds provide all of the essential amino acids the body [...]

“The anniversary of my brother’s death is on the 26 of July. He was killed 27 years ago,” says Robinson Salas. Robinson is one of the millions of people who had been displaced from their homes and their lands by the armed conflict between the Government of Colombia and the FARC (Revolutionary Armed Forces of Colombia) rebel group. This 52-year [...]

On July 31, 1971, Al Worden performed the first deep-space extra-vehicular activity. "No one in all of history" saw what he saw that day

Two sites preserve around 50 footprints, a discovery that highlights the richness of prehistoric life on the island

A new theory suggests the hot, harsh planet’s interior could have contained volatiles like water

The impact that created Pluto’s 'heart' may have rippled through its ocean and damaged its rear

Geoscientists noticed the normal rumbles of human activity picked up by their instruments have died down as much of the world ground to a halt

These dairy products are no longer edible, but they're still valuable to researchers

Doctors and nurses are attaching smiling photos of themselves to the outside of their protective gear to maintain connections with patients

Traditionalist "two-spacers" can still disable the function

The freedom fighter may have once used the structure to conspire against English forces

The solitary species is hard to spot on camera, and they're the only canine that lives in the Amazon rainforest

Catch the musical event, featuring Sting, Death Cab for Cutie front man Ben Gibbard and other artists, on YouTube tonight at 8 p.m. Eastern time

Venturing into the wilderness for often weeks at a time, nature photographer Dawn LaPointe is used to social distancing

In New York City, a desperate need among healthcare workers has pushed to the forefront the question: Is homemade equipment safe to use?

The new book 'The Rainbow Atlas' invites readers on a vivid journey across the globe

Why not use quarantine as an opportunity to have your homeschoolers master woodworking or engine repair?

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

Rice terraces in Longji,China.

The National Trust for Historic Preservation is looking for 1,000 places tied to women's history, and to share the stories of the figures behind them

The N.W.T. and Nunavut Workers’ Safety and Compensation Commission says it filed multiple charges in the Nunavut Court of Justice under the Nunavut Safety Act on May 1.

The remote cabin could be the difference between life and death for travellers stuck on the territory’s long winter road. It was built to remember Stella Barnaby, who would have been 55 this Saturday.

Seven people were displaced by a fire early Saturday on the north end of Saint John.

Police in Thunder Bay have arrested and charged a man from the northwestern Ontario city following an investigation into allegations of child luring.

The Art Zone is a place where teens can creatively express themselves and their worship for God. For Saskia, art is a way to quiet her mind and let God speak.

This paper studies the relationship between bank geographic complexity and risk. We use a unique dataset of 96 bank holding companies around the world to measure the geographic dispersion of their affiliates. We study how this dispersion interacts with economic and regulatory conditions to affect the riskiness of the bank.

Baltimore Orioles outfielder and first baseman Trey Mancini revealed Tuesday he is in the midst of six months of chemotherapy as he fights Stage III colon cancer.

Sheldon Lavers didn't leave his window for hours Friday night as police negotiated with a man next door who they believed had a gun and was smashing items inside.

Quebec Health Minister Danielle McCann says the government is evaluating whether to allow the world figure skating championships to go ahead next week in Montreal.

See the Full Flower Moon, last supermoon of 2020, bloom in these stunning photos  Space.comIn Pictures: 'Full-flower supermoon' amid coronavirus lockdowns  Aljazeera.comIn pics | Last supermoon in 2020: Stunning views from around th...

The Canada-wide chain will introduce a mandatory mask policy on May 11, claiming customers and employees want a policy more in line with how Asian countries have handled the COVID-19 crisis.

Waterloo regional police have charged three people and identified a suspect in a fatal February hit and run on Highland Rd. W.

Laurent Duvernay-Tardif and the Kansas City Chiefs have agreed to a restructured deal for the Canadian offensive lineman.

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

This crisis is exposing the savagery of American democracy.