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.

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.

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.

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.

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.

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.

OM teaches East London youth about the persecuted Christians in the world, as well as trains them in street ministry.

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

While other couples in their fifties talk about retirement, Philip and Riana Dyason are talking about a new beginning: pioneer ministry in Russia.

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

Opening a ‘baby safe’ in a township near Pretoria, South Africa, helps desperate mothers find a solution and give their babies a future.

OM team members Tami and Alu share how henna opens doors to the hearts of the Somali people, living in Cape Town.

God sustained MDT participant David, who found it difficult co-leading his short-term outreach when he wasn't doing so well himself.

Australian outreach participant Kathryn Jenkin testifies to how God used her prayers while on outreach in Lesotho.

In July, an OM team of artists will use their creative gifts to share about the Creator at the National Arts Festival in Grahamstown.

The AIDS Hope team encourages children in their afterschool program in Mamelodi to share the gospel with the community.

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

The OM Russia Discipleship Centre opens its doors to 13 new students in September and opens a second OM building on the site.

OM Russia’s Student Christian Centre, in partnership with the local Evangelical Church, reaches universities in Novosibirsk. The project leader shares about plans for this year.

The students of OM Russia's Discipleship Centre practice sharing their faith with those from a Muslim background.

Dorothea, from Germany, joins the one-year programme with OM Russia, which includes visiting Siberian villages to help churches and sharing the Gospel with locals.

OM Russia's short-term outreach team travels across Russia sharing about Christ with as many travellers as possible.

Students at OM Russia’s Discipleship Centre help plant churches, start a rehab centre and begin a farming business.

A team member from the USA who participated in a short-term trip on the Trans-Siberian railroad across Russia shares her experience.

An OM worker in Russia finds opportunities to share Christ's love with members of the Romani ethnic group.

After discovering his freedom in Christ and being discipled, former drug addict Ruslan wants to share hope with the least reached.

Nineteen boys and girls graduated from Fishport Kids Tutorial Club's day care programme in Manila, Philippines, this month.

The OM Philippines-Cebu team, in partnership with the local church, touches the lives of young and old through a five-day Bible class.

Students from OM Philippines-Cebu's Alternative Learning System bring children joy through a Christmas party, following the trauma caused by Bohol earthquake and Typhoon Haiyan.

From Leyte Island to Northern Cebu to Bohol Island, the Christmas season brought overwhelming joy to many who received provision and care from OM Philippines.

Over 50 pastors and family members from Tacloban enjoy a weekend getaway organised by OM Philippines from 7-9 March.

OM Philippines completes their annual mission training and exposure programme in the tribal areas of Palawan, Philippines.

OM Philippines received a huge donation of brand new clothing, shoes and food packs for Typhoon Haiyan victims.

Six young people joined STEP OUT 2014 and an outreach in the Philippines to challenge their comfort zones, and they were not disappointed.

Three boys who sell fish become “men of peace” for the DreamAsia+ team in three of the poorest Muslim communities in the Philippines.

One hundred Filipino teens, aged 12-18 are expected to come to the five-day event of fun, learning and life-changing encounters in Cebu.

After over 10 years of praying, the Philippines had its first-ever TeenStreet!

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

Focusing on one person at a time, John uses everyday life as a way to meet people where they are and journey alongside them.

“God is working in this community,” James said. He and other Christians in his village are challenging the culture by living their lives for Christ.

Long-termers in Turkey get an unexpected opportunity to share the gospel while also representing the Turkish Post Office!

An OMer in Turkey who likes to bake is able to bless her neighbours in their apartment block.

A Turkish girl's long journey to becoming a believer in Jesus.

OM Turkey helps the local church to minister to the 2.6 million refugees in their country.

No known believers from a Muslim background existed in Turkey when the first two OMers arrived in 1961. Now, nearly half of the 7,000 believers there can trace their journey through the Bible Correspondence Course.

Long-term workers in Turkey are seeing openness to the gospel like they haven't in many years. They share some recent stories here.

Three Turkish women have discovered the Saviour who loves them through contact with the Bible Correspondence Course in Istanbul, Turkey.

An OM Lifehope team member discovers a new way of reaching out to people on the street through henna designs.

Members of Christ Church in Lye and OM’s local team visit neighbourhoods to invite residents to church, hand out tracts or hear prayer requests.

When an OM Lifehope team, partnering with On the Move International, held their annual community barbeque, they did something a little different.