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Prescribing sodium oxybate for narcolepsy




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South Dakota illegally placed disabled people in nursing homes, federal investigation finds




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“Impressive results” in stem cell treatment for multiple sclerosis




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Seven days in medicine: 8-14 June 2016




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Disease modifying therapies for relapsing multiple sclerosis




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Potential role for BCG in treatment of autoimmune diseases




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Projecting Vlad Jr.'s first 10 seasons

If Vladimir Guerrero Jr. can handle the hot corner -- at least for a while -- that would be gravy. The real attraction is the bat, and if these projections are any indication, it may be a special one.




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This is the Blue Jays prospect to watch in camp

The countdown to pitchers and catchers reporting is down to single digits for all 30 MLB clubs, but as exciting as it is to see the return of Major League stars, it's also a time to dream about the next wave of baseball talent.




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Jansen among biggest prospect bargains

Considering the players that get the big bucks often get most of the attention when they are signed and drafted, let's take some time to look at the other end of the spectrum. Here are the biggest steals on the Top 100 Prospects list.




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Here's your guide to Blue Jays Spring Training

The Blue Jays are less than one week away from the start of Spring Training. Here's a brief rundown of everything fans need to know before the Grapefruit League season officially begins.




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Inbox: Who are Blue Jays' sleeper prospects?

What unheralded prospect could break out in 2019? Beat reporter Gregor Chisholm answers that and more in this edition of the Inbox.




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Blue Jays' hope for 2019 lies in the future

The Blue Jays spent the past two years clinging to the past. Now, they're embracing the future.




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Vlad Jr. ready to take center stage this spring

No matter what happens this spring, the player everyone is going to be talking about on a daily basis is Vladimir Guerrero Jr.




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Predicting Blue Jays' Opening Day roster

The start of Spring Training is almost here and it's time for the annual tradition of predicting the Blue Jays' 25-man roster. MLB.com will revisit these projections midway through camp, and then again at the end of Spring Training to see how close we came.




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Who's coming, who's going in Toronto rotation?

As MLB.com continues its annual Around the Horn series, it's time to take a closer look at the Blue Jays' starting rotation. It looks different now than it did a few months ago and it probably won't be long before the same thing will be said again because these changes are far from over.




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Roster in transition as Blue Jays open camp

Charlie Montoyo is about to embark on the first spring of his managerial career, and based on the number of decisions he has to make, it's going to be a challenging six weeks.




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One rotation spot up for grabs, Atkins says

The Blue Jays were barely one hour into the official start of Spring Training when general manager Ross Atkins threw the first curveball of the year. The news wasn't so much who made the list, but rather who did not. Despite an impressive 2018 rookie season, lefty Ryan Borucki apparently hasn't been guaranteed anything quite yet.




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Blue Jays latest to embrace spin-rate machine

The Blue Jays have followed the lead of several other teams around Major League Baseball by using a Rapsodo machine to analyze spin-rate data. A Rapsodo camer is used to understand how much movement, velocity and spin pitchers are getting on every toss.




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Sanchez impresses in first spring bullpen

Blue Jays manager Charlie Montoyo was so impressed with Aaron Sanchez's first bullpen session of the spring that it would have been almost impossible to wipe the smile off his face afterwards.




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WATCH: Vlad Jr. takes his first spring cuts

MLB.com's beat reporters have you covered with the action from every team's training camp. Keep track of the latest highlights of Spring Training right here.




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Vlad Jr. draws praise upon spring arrival

The Blue Jays' biggest star arrived Saturday morning when top prospect Vladimir Guerrero Jr. officially reported to Spring Training. Guerrero took part in a few rounds of batting practice and hit at least one ball out of the park. The Dominican native is expected to speak to the media Monday for the first time this spring as he sets out to begin his first full Major League Spring Training.




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GM Atkins responds to comments by Stroman

Blue Jays general manager Ross Atkins declined to get into a back-and-forth with Marcus Stroman on Sunday afternoon, sidestepping criticism of the organization from his right-handed starter.




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The Blue Jays' Spring Training battle to watch

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.




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Galvis planning to be Blue Jays' regular SS

Freddy Galvis conceded things might eventually change, but the veteran infielder is under the impression that he will be the Blue Jays' everyday shortstop at the start of the season.




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Vlad Jr. diplomatic in discussing MLB time frame

With each passing day, the hype continues to grow around Vladimir Guerrero Jr., but MLB Pipeline's top-ranked prospect seems to be keeping a pretty level head throughout all the chaos.




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Re: Workplace violence stems from deep rooted problems within the Indian medical system




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Re: Assisted dying bill: Two doctors would need to approve action




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Correspondence on 'Dispute arises over World Professional Association for Transgender Health’s involvement in WHO’s trans health guideline' by Jennifer Block




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Re: Patient involvement in developing clinical guidelines




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Disinformation enabled Donald Trump’s second term and is a crisis for democracies everywhere

Donald Trump did not win the 2020 election, but asserting that he did became a prerequisite for Republicans standing for nomination to Congress or the Senate to win their primaries. An entire party became a vehicle for disinformation.1 Trump did win the 2024 presidential election, and key to that victory was building on the success of that lie. If you control enough of the information ecosystem, truth no longer matters.Another telling example: Haitian migrants in Springfield, Ohio, are not eating cats and dogs. US vice president elect, JD Vance, the source of that claim, admitted as much even as he justified it. “If I have to create stories so that the American media actually pays attention to the suffering of the American people, then that’s what I'm going to do,” he said.2Disinformation in politics is nothing new. History is replete with claims that were fabricated to advance political aims. Although...




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Assisted dying bill: Two doctors would need to approve action

Terminally ill adults in England and Wales who are expected to die within six months would be able to get help to end their lives if their applications were approved by two doctors and a High Court judge, under proposed new legislation.1Labour MP Kim Leadbeater, who proposed the bill, said it provided the “strictest safeguards anywhere in the world.” The law would apply only to people who have full mental capacity and are terminally ill. Mental illness and disability are both excluded as eligibility criteria, and a person would need to declare twice in writing that they wanted to be helped to die.A person who wished to end their life would have to administer the medication themselves. It will remain illegal for a doctor or anybody else to end a person’s life. No doctor will be obliged to participate in any part of the process.The bill would also make it...




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Malcolm Donaldson: paediatric endocrinologist, musician, and proud collaborator with his wife Julia, author of The Gruffalo

bmj;387/nov12_10/q2481/FAF1faJulia and Malcolm Donaldsondonaldson20241111.f1Malcolm Donaldson was a distinguished paediatric endocrinologist with a string of research publications to his name—but he was also happy to play second fiddle (almost literally) to his wife Julia, the celebrated author of much loved children’s books, including The Gruffalo and Room on the Broom.Malcolm, a talented musician and performer, accompanied his wife as she toured festivals, schools, and libraries in the UK and around the world. Together they performed the stories, with Malcolm acting characters ranging from an accident prone dragon to a comic cattle thief. His star role, in the words of Julia’s literary agent, was “a particularly suave fox” in The Gruffalo.Malcolm met Julia Shields when they were students at the University of Bristol and they married in 1972. Donaldson went on to work in Brighton, London, and Lyon, France, before moving back to Bristol to be a senior registrar in paediatrics. Six...




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Scarlett McNally: GPs and geriatricians can help to improve shared decision making for surgical patients

At one of my first meetings as an elected council member of the Royal College of Surgeons of England, we approved a report called Access All Ages. It encouraged less ageist thinking and bias among healthcare staff that might lead to them denying older people surgery.1 But sometimes an operation isn’t the best option. Among patients who have surgery, 14% express regret and 15% experience complications, which are at least four times as likely if they’re frail or physically inactive.2 The Centre for Perioperative Care has published information on the importance of exercise before surgery,3 but that alone may not be enough.We need shared decision making,4 including asking patients what matters to them. The public should be primed to ask about BRAN—the benefits, risks, and alternatives to surgery and the likely result from doing nothing.4 A slew of data supports this approach, especially from the POPS initiative (Perioperative Care of...




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Spain takes stock of flood damage

bmj;387/nov13_11/q2490/FAF1faDavide Bonaldo/SOPA/Sipa/AlamyThe devastating power and impact of the flash floods that swept through eastern Spain from 29 October is captured in this image from the city of Valencia. More than 200 people are known to have been killed—and around 100 are still missing—in floods caused by rivers and normally dry canals bursting their banks after torrential rain across the region.Medical sites have been severely hit, with several towns setting up temporary clinics in sports centres for essential services. A local GP told Medscape Network that because many roads were closed it was difficult for people to reach these makeshift facilities.In an effort to combat this the Valencia region’s health ministry has established a register of volunteer health professionals available to help in affected areas. It has also launched a public health campaign warning of the spread of infectious diseases made possible by damage to the sanitation infrastructure, including leptospirosis, tetanus,...




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Cardiovascular disease: Just one in 12 eligible people had health check last year, watchdog finds

The current system for delivering NHS cardiovascular disease (CVD) health checks is not working effectively and must be reviewed to ensure that it reaches people with the highest risk, the National Audit Office has said.1In a review of the commissioning, delivery, and performance of CVD health checks the watchdog found that just over one in 12 people (8.8%) who were eligible attended a health check in 2023-24—which, if maintained, would equate to a five year coverage of 44%.Health checks were first introduced in 2009, with the aim of reducing ill health from CVD by offering everyone aged 40-74 without a pre-existing heart condition a check-up every five years. However, problems have arisen since the responsibility for commissioning these checks was transferred to local authorities in 2013, said the National Audit Office.The move led to the Department of Health and Social Care (DHSC) losing its ability to influence local authority performance,...




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Monosynaptic Inputs to Ventral Tegmental Area Glutamate and GABA Co-transmitting Neurons

A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes.




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Behavioral and Neural Mechanisms of Face-Specific Attention during Goal-Directed Visual Search

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Compared with distractors, fixations on targets reduced spike–LFP coherence within the temporal cortex. Importantly, target-induced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks.




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Encoding of Vibrotactile Stimuli by Mechanoreceptors in Rodent Glabrous Skin

Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in the rodent glabrous skin has received scant attention, unlike in primates where the glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability), whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in male rats and mice of either sex, we measured the reliability and precision of LTMR responses to tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RA1 and RA2/Pacinian afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that coactivation patterns play a greater role in population coding than for dichotomously tuned primate RAs.




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Monocyte Invasion into the Retina Restricts the Regeneration of Neurons from Müller Glia

Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina.




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A Prefrontal->Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats’ active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC->vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal->midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.




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Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field of two male rhesus monkeys shifting gaze to a target while a distractor with the same eccentricity appeared either left or right of the target at various delays after target presentation. We found that the population level of presaccadic activity of neurons representing the distractor location encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature toward the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved toward distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push–pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets.




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Deciphering Peripheral Taste Neuron Diversity: Using Genetic Identity to Bridge Taste Bud Innervation Patterns and Functional Responses

Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neurons mirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by the neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli—sour, bitter, and high salt concentrations—as compared with the full taste population. Penk+ neurons are less likely to respond to nonaversive stimuli—sucrose, umami, and low salt—compared with the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus.




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The Role of the Rat Prefrontal Cortex and Sex Differences in Decision-Making

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. μ-Opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process toward high-value stimuli. These effects were observed without any impact on the rats’ choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when," but not "how," to act.




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This Week in The Journal




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Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS– cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), a major reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior.




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Protecting the women and girls of South Africa

HIV and AIDS can be prevented. It just takes you.




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Cycling to the unreached

Staff from OM SportsLink and Campus Crusade for Christ cycled from Pretoria to Cape Town to minister to people in rural villages along the way.




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Praying for change

After seeking God to change his current course, Hein van der Merwe attends a five-day programme at OM South Africa and finds new direction.




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Preparing for missions

Engage, OM South Africa’s bi-annual conference, provides a challenge and a channel for joining missions with OM.




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Introducing basketball to Mamelodi

Basketball is not played much in South Africa, but OM SportsLink successfully introduces the game to students in Mamelodi, a township outside of Pretoria.