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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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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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Neural Predictors of Fear Depend on the Situation

The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ~20 s clips depicting spiders, heights, or social encounters and rated fear after each video. Searchlight multivoxel pattern analysis was used to identify whether and which brain regions carry information that predicts fear experience and the degree to which the fear-predictive neural codes in these areas depend on or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation-dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern but rather a collection of multiple heterogeneous brain states.




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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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The Link in South Africa

Five OM entities based in South Africa previously working in three separate offices throughout Pretoria have recently united under one roof.




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UNIC ministers to students

Unite Nations in Cape Town (UNIC) works alongside two local universities, building friendships with the international students for God’s kingdom.




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Voicing the plight of the vulnerable

In October, 140 people take the Table Mountain Challenge in Cape Town and Franschhoek, South Africa, as part of the Freedom Climb.




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OM South Africa appoints new leader

On 23 January 2015, OM South Africa celebrated Pranesh Anandlal’s leadership as director since 2008 and welcomed his successor, Andrè van der Bergh.




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Loving youth through sports in South Africa

OMer Jan Willem Otten uses basketball as a way to keep kids off the streets and put them in touch with the gospel




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Dabbling in the office of dreams

For the OM Africa communications and media team, the latest and greatest thing is a duck.




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From Argentina to Africa

Belen, 20, discovers she doesn't need to wait to serve God in missions when He sends her to Africa for six weeks.




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From card making to vehicle servicing

OM Russia’s Business for Transformation ministry supports eight projects that empower locals through employment, while impacting the kingdom.




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OM Philippines participates in Run for the World

OM SportsLink hosts a local R4TW race to engage those involved with OM Philippines-Cebu Ministries and encourage people to pray for the nations.




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School drop-outs receive holistic education

OM Philippines’ Alternative Learning System teachers visit the homes of students in an effort to connect with their parents and encourage further education.




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Surigao City earthquake victims need trauma counselling

OM Philippines send staff to assess the earthquake damages in Surigao City and provide needed disaster relief training.




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Tropical cyclone reopens conflict area

OM responded to the needs of people affected by Typhoon Vinta, relying on military accompaniment to reach the location and deliver aid.




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Public transport for public proclamation

Two OM workers share the gospel while riding on buses in Turkey.




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Communications and Jesus

Three communications interns serving with OM Lifehope in the UK share their experiences and why people should consider using their God-given gifts in missions.




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Treating physical and spiritual needs

Meet one woman who serves God as the only community health worker for over 2,000 people in six remote villages of Zambia.




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Healing clinics

A local church group's visit to a clinic in central Greece.




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Former drug addict works with homeless in Athens

After working with the needy on a Transform 2012 outreach to Greece, Anthony (UK) returned to Athens to continue in that ministry.




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Tragic accident brings salvation to village

A Roma man’s cry to God for mercy to spare his son’s life transforms his future and the future of his small town.




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Surprising danger, quick reaction, God's protection

Faith is strengthened when OMers learn how the Lord watches over them, not allowing harm to come to the people or the ministry.




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From Latin America to the Levant

OM workers explain, their home has become a mix of Latin American and Middle Eastern cultures.




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Running at full capacity: Evangelicals serve refugees in Lebanon

Five years of displacement has taken its toll on Syrian refugees living in Lebanon, but many have met Jesus and discovered eternal hope.




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North Africans prepare to go to Iraq

The OM Near East Field church planting school prepares students to cross cultural and religious boundaries.




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The power of music

A children’s music programme helps Syrian mothers identify their skills and how to use them for Christ, even before they become believers.




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Communicating art whole-heartedly

A team of artists from the OM Arts School of Mission reach out locally to people with special needs in Val Pellice, Italy.




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OM Italy launches anti-trafficking ministry 

The coordinator of OM Italy’s anti-trafficking ministry describes the birth of the ministry through meeting a Nigerian woman forced into prostitution in Rome.




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Summer camp in the Val Pellice Valley

OM Italy organises an annual summer camp for children in Torre Pellice, where many hear the gospel for the first time.




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Transform outreach casts vision for trafficking ministry

Participating in a Transform outreach to trafficked women gave OMer Erika Tello the vision of founding the OM Italy anti-trafficking ministry.




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Around the walls of the Vatican

An Italian girl receives a vision of Jericho that guides her to speak with a woman on Transform 2013 outreach day.




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Prophetic art for the people of Isola del Gran Sasso

OM Arts artists participating in the Incarnate programme in Italy create a collaborative piece of prophetic art for the local community.




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Anti-Trafficking in Italy

The anti-trafficking efforts by OM Italia are developing as they work to involve the local church in this outreach.




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Norway Marine Office approves internship opportunities with Logos Hope

In January 2013, OM Norway and Norwegian Naval Training Agency agreed on internship programme for deckhands and motormen on board MV Logos Hope.




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First Gurbet-Serbian-English picture dictionary

“This publication is a tool to help those who will join Goran in sharing the gospel among Gurbet-speaking Roma, and lays the foundation for future Christian materials.”




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Reflecting God in the outskirts of Zurich

The OM short-term team seek God’s will for their ministry after their move to the outskirts of Zurich. Recent encounters have encouraged and surprised them.




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Practical help opens hearts

OM Bosnia supplies firewood to locals and an invitation to the local church for dinner, which opens their hearts to the truth.




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Czech medical workers trek for Christ

In the spring of 2011, a team from OM Czech Republic trekked in a remote area of the Himalayas on a four-week medical mission.




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Anti-human trafficking training in South Africa

In the summer of 2013, a South African member of OM Czech Republic returned to her home country to lead anti-trafficking training and awareness seminars.




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Medical mission to Ghana

OM Czech Republic engaged in a medical mission outreach and evangelism ministry to villages in northern Ghana.




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Licht in einer traurigen Realität

Gerechtigkeit zu den Unterdrückten zu bringen ist ein Auftrag für jeden Christen, sagt Natasha Shoultz, die unter Frauen in Prostitution in Prag arbeitet.




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Bringing hope to workers in the sex industry in Czech Republic

The ministry of helping women involved in the sex industry aims to support those trafficked in Czech Republic by building relationships and prayer




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God’s light shines in the darkness of the sex trade – in Czech Republic

As OM Czech Republic team members reach out to sex workers by visiting a brothel regularly, they are able to establish friendships and talk about God and His care for the women there, and offer them Christmas gifts, which touch hearts.




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Fighting human trafficking in Ecuador

Human trafficking grows like a cancer in Ecuador. Boris and Fernanda Salinas are destined to fight it.




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Impacting survivours of trafficking one climb at a time

“I climb in the name of the young women we serve,” said Boris Salinas, who will participate in a Freedom Climb event on 26 April.