Touch neurons underlying dopaminergic pleasurable touch and sexual receptivity.

Pleasurable touch is paramount during social behavior, including sexual encounters. However, the identity and precise role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice. Here, we study the social relevance of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking dorsiflexion resembling the lordotic copulatory posture. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopamine release in the nucleus accumbens. Together, these findings establish that Mrgprb4-lineage neurons initiate a skin-to-brain circuit encoding the rewarding quality of social touch.

Intermittent fasting in the prevention and treatment of cancer.

Chronic caloric restriction (CR) has powerful anticarcinogenic actions in both preclinical and clinical studies but may be difficult to sustain. As an alternative to CR, there has been growing interest in intermittent fasting (IF) in both the scientific and lay community as a result of promising study results, mainly in experimental animal models. According to a survey by the International Food Information Council Foundation, IF has become the most popular diet in the last year, and patients with cancer are seeking advice from oncologists about its beneficial effects for cancer prevention and treatment. However, as discussed in this review, results from IF studies in rodents are controversial and suggest potential detrimental effects in certain oncologic conditions. The effects of IF on human cancer incidence and prognosis remain unknown because of a lack of high-quality randomized clinical trials. Preliminary studies suggest that prolonged fasting in some patients who have cancer is safe and potentially capable of decreasing chemotherapy-related toxicity and tumor growth. However, because additional trials are needed to elucidate the risks and benefits of fasting for patients with cancer, the authors would not currently recommend patients undergoing active cancer treatment partake in IF outside the context of a clinical trial. IF may be considered in adults seeking cancer-prevention benefits through means of weight management, but whether IF itself affects cancer-related metabolic and molecular pathways remains unanswered.

Long-term effects of climate change on juvenile bull shark migratory patterns.

Seasonal variability in environmental conditions is a strong determinant of animal migrations, but warming temperatures associated with climate change are anticipated to alter this phenomenon with unknown consequences. We used a 40-year fishery-independent survey to assess how a changing climate has altered the migration timing, duration and first-year survival of juvenile bull sharks (Carcharhinus leucas). From 1982 to 2021, estuaries in the western Gulf of Mexico (Texas) experienced a mean increase of 1.55°C in autumn water temperatures, and delays in autumn cold fronts by ca. 0.5 days per year. Bull shark migrations in more northern estuaries concomitantly changed, with departures 25-36 days later in 2021 than in 1982. Later, migrations resulted in reduced overwintering durations by up to 81 days, and the relative abundance of post-overwintering age 0-1 sharks increased by >50% during the 40-year study period. Yet, reductions in prey availability were the most influential factor delaying migrations. Juvenile sharks remained in natal estuaries longer when prey were less abundant. Long-term declines in prey reportedly occurred due to reduced spawning success associated with climate change based on published reports. Consequently, warming waters likely enabled and indirectly caused the observed changes in shark migratory behaviour. As water temperatures continue to rise, bull sharks in the north-western Gulf of Mexico could forgo their winter migrations in the next 50-100 years based on current trends and physiological limits, thereby altering their ecological roles in estuarine ecosystems and recruitment into the adult population. It is unclear if estuarine food webs will be able to support changing residency patterns as climate change affects the spawning success of forage species. We expect these trends are not unique to the western Gulf of Mexico or bull sharks, and migratory patterns of predators in subtropical latitudes are similarly changing at a global scale.

COVID-19 passenger screening to reduce travel risk and translocation of disease.

Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.

The risk of contact between visitors and Borrelia burgdorferi-infected ticks is associated with fine-scale landscape features in a southeastern Canadian nature park.

BACKGROUND: Infectious diseases are emerging across temperate regions of the world, and, for some, links have been made between landscapes and emergence dynamics. For tick-borne diseases, public parks may be important exposure sites for people living in urbanized areas of North America and Europe. In most cases, we know more about the ecological processes that determine the hazard posed by ticks as disease vectors than we do about how human population exposure varies in urban natural parks. METHODS: In this study, infrared counters were used to monitor visitor use of a public natural park in southern Quebec, Canada. A risk index representing the probability of encounters between humans and infected vectors was constructed. This was done by combining the intensity of visitor trail use and the density of infected nymphs obtained from field surveillance. Patterns of risk were examined using spatial cluster analysis. Digital forest data and park infrastructure data were then integrated using spatially explicit models to test whether encounter risk levels and its components vary with forest fragmentation indicators and proximity to park infrastructure. RESULTS: Results suggest that, even at a very fine scales, certain landscape features and infrastructure can be predictors of risk levels. Both visitors and Borrelia burgdorferi-infected ticks concentrated in areas where forest cover was dominant, so there was a positive association between forest cover and the risk index. However, there were no associations between indicators of forest fragmentation and risk levels. Some high-risk clusters contributed disproportionately to the risk distribution in the park relative to their size. There were also two high-risk periods, one in early summer coinciding with peak nymphal activity, and one in early fall when park visitation was highest. CONCLUSIONS: Here, we demonstrate the importance of integrating indicators of human behaviour visitation with tick distribution data to characterize risk patterns for tick-borne diseases in public natural areas. Indeed, understanding the environmental determinants of human-tick interactions will allow organisations to deploy more effective risk reduction interventions targeted at key locations and times, and improve the management of public health risks associated with tick-borne diseases in public spaces.

Virtual Visit Trends in Nursing Homes During the COVID-19 Pandemic.

Background: Physical distancing and visiting restrictions during the COVID-19 pandemic particullarly posed significant challenges in providing timely medical care in nursing homes. Virtual visits were pivotal in providing both scheduled and urgent patient care in addition to in-person care when possible. These virtual visits could have been used to provide urgent medical care than the regular scheduled visits. We hypothesize that regular non-COVID-19-related virtual visits in the evaluated nursing home facilities were lower than COVID-19-related virtual visits during this period. The objective was to compare the frequency of COVID-19-related virtual visits with non-COVID-19-related virtual visits performed in three suburban nursing homes in Michigan from December 2020 through February 2022. Methods: Retrospective chart review of 283 patients, comprising 563 virtual visits. The most frequent ICD-10 diagnostic codes used by providers for primary encounters were analyzed for three participating facilities Results: Only 13.8% (78/563) of all virtual visits during the study period were for COVID-19 as a primary encounter. In total 86.1% (485/563) of visits were non-COVID-19 related, which comprised most frequently M6281 muscle weakness (45), E119 diabetes type with complications (20), NI86 end-stage renal disease (11), N390 urinary tract infection (10), G309 Alzheimer's disease (10), and I4891 unspecified atrial fibrillation (10). Conclusion: We found that the primary ICD-10 diagnosis codes for virtual COVID-19-related visits were significantly lower than non-COVID-19-related virtual visits in our study population. This trend could be associated with multiple system-based factors. Further studies to examine factors responsible for these findings are warranted.

Short Report on Effectiveness of an Autistic-Delivered Peer Support Program: Preliminary Results.

There is little research on the effectiveness of autistic peer-delivered services. This study examines early outcomes associated with the Community Autism Peer Specialist program (CAPS), which was created in partnership with autistic individuals and is delivered by autistic adults who have received training in the delivery of peer support services to enhance the community functioning of autistic youth and adults. A single group pre-test/post-test design was used to examine early outcomes in the areas of independent living needs, social functioning, service engagement, and quality of life. A total of 23 individuals with autism aged 14-41 years were included in the study. Reductions were found in social functioning impairments and unmet needs after three months in the program. Participants also reported greater engagement in mental health services and activities that promote wellness compared with before the program. This study suggests that peer support services delivered by autistic peers may be an effective intervention approach for autistic youth and adults. Future studies with a more rigorous study design (e.g., randomized controlled trials), a larger sample size, and longer-term outcome measurements are needed to further investigate the effectiveness of CAPS and similar autistic-delivered services.

Using Serum Specimens for Real-Time PCR-Based Diagnosis of Human Granulocytic Anaplasmosis, Canada.

Whole blood is the optimal specimen for anaplasmosis diagnosis but might not be available in all cases. We PCR tested serum samples collected in Canada for Anaplasma serology and found 84.8%-95.8% sensitivity and 2.8 average cycle threshold elevation. Serum can be acceptable for detecting Anaplasma spp. when whole blood is unavailable.

Widespread Exposure to Mosquitoborne California Serogroup Viruses in Caribou, Arctic Fox, Red Fox, and Polar Bears, Canada.

Northern Canada is warming at 3 times the global rate. Thus, changing diversity and distribution of vectors and pathogens is an increasing health concern. California serogroup (CSG) viruses are mosquitoborne arboviruses; wildlife reservoirs in northern ecosystems have not been identified. We detected CSG virus antibodies in 63% (95% CI 58%-67%) of caribou (n = 517), 4% (95% CI 2%-7%) of Arctic foxes (n = 297), 12% (95% CI 6%-21%) of red foxes (n = 77), and 28% (95% CI 24%-33%) of polar bears (n = 377). Sex, age, and summer temperatures were positively associated with polar bear exposure; location, year, and ecotype were associated with caribou exposure. Exposure was highest in boreal caribou and increased from baseline in polar bears after warmer summers. CSG virus exposure of wildlife is linked to climate change in northern Canada and sustained surveillance could be used to measure human health risks.

Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL.

Chimeric antigen receptor (CAR)-T-cell therapeutic efficacy is associated with long-term T-cell persistence and acquisition of memory. Memory-subset formation requires T-cell factor 1 (TCF-1), a master transcription factor for which few regulators have been identified. Here, we demonstrate using an immune-competent mouse model of B-cell acute lymphoblastic leukemia (ALL; B-ALL) that Regnase-1 deficiency promotes TCF-1 expression to enhance CAR-T-cell expansion and memory-like cell formation. This leads to improved CAR-T-mediated tumor clearance, sustained remissions, and protection against secondary tumor challenge. Phenotypic, transcriptional, and epigenetic profiling identified increased tumor-dependent programming of Regnase-1-deficient CAR-T cells into TCF-1+ precursor exhausted T cells (TPEX) characterized by upregulation of both memory and exhaustion markers. Regnase-1 directly targets Tcf7 messenger RNA (mRNA); its deficiency augments TCF-1 expression leading to the formation of TPEX that support long-term CAR-T-cell persistence and function. Regnase-1 deficiency also reduces exhaustion and enhances the activity of TCF-1- CAR-T cells. We further validate these findings in human CAR-T cells, where Regnase-1 deficiency mediates enhanced tumor clearance in a xenograft B-ALL model. This is associated with increased persistence and expansion of a TCF-1+ CAR-T-cell population. Our findings demonstrate the pivotal roles of TPEX, Regnase-1, and TCF-1 in mediating CAR-T-cell persistence and recall responses, and identify Regnase-1 as a modulator of human CAR-T-cell longevity and potency that may be manipulated for improved therapeutic efficacy.

Breaking Rayleigh's Law with Spatially Correlated Disorder to Control Phonon Transport.

Controlling thermal transport in insulators and semiconductors is crucial for many technological fields such as thermoelectrics and thermal insulation, for which a low thermal conductivity (κ) is desirable. A major obstacle for realizing low κ materials is Rayleigh's law, which implies that acoustic phonons, which carry most of the heat, are insensitive to scattering by point defects at low energy. We demonstrate, with large scale simulations on tens of millions of atoms, that isotropic long-range spatial correlations in the defect distribution can dramatically reduce phonon lifetimes of important low-frequency heat-carrying modes, leading to a large reduction of κ-potentially an order of magnitude at room temperature. We propose a general and quantitative framework for controlling thermal transport in complex functional materials through structural spatial correlations, and we establish the optimal functional form of spatial correlations that minimize κ. We end by briefly discussing experimental realizations of various correlated structures.

Molecular networks in atopic mothers impact the risk of infant atopy.

BACKGROUND: The prevalence of atopic diseases has increased with atopic dermatitis (AD) as the earliest manifestation. We assessed if molecular risk factors in atopic mothers influence their infants' susceptibility to an atopic disease. METHODS: Pregnant women and their infants with (n = 174, high-risk) or without (n = 126, low-risk) parental atopy were enrolled in a prospective birth cohort. Global differentially methylated regions (DMRs) were determined in atopic (n = 92) and non-atopic (n = 82) mothers. Principal component analysis was used to predict atopy risk in children dependent on maternal atopy. Genome-wide transcriptomic analyses were performed in paired atopic (n = 20) and non-atopic (n = 15) mothers and cord blood. Integrative genomic analyses were conducted to define methylation-gene expression relationships. RESULTS: Atopic dermatitis was more prevalent in high-risk compared to low-risk children by age 2. Differential methylation analyses identified 165 DMRs distinguishing atopic from non-atopic mothers. Inclusion of DMRs in addition to maternal atopy significantly increased the odds ratio to develop AD in children from 2.56 to 4.26. In atopic compared to non-atopic mothers, 139 differentially expressed genes (DEGs) were identified significantly enriched of genes within the interferon signaling pathway. Expression quantitative trait methylation analyses dependent on maternal atopy identified 29 DEGs controlled by 136 trans-acting methylation marks, some located near transcription factors. Differential expression for the same nine genes, including MX1 and IFI6 within the interferon pathway, was identified in atopic and non-atopic mothers and high-risk and low-risk children. CONCLUSION: These data suggest that in utero epigenetic and transcriptomic mechanisms predominantly involving the interferon pathway may impact and predict the development of infant atopy.

Unrealized Cross-System Opportunities to Improve Employment and Employment-Related Services Among Autistic Individuals.

Policy Points Employment is a key social determinant of health and well-being for the estimated 5.4 million autistic adults in the United States-just as it is for citizens without disabilities. Evaluation and monitoring of publicly funded employment services is paramount given the dramatic increases in adults with autism who need job supports. Vocational Rehabilitation agencies appeared to be absorbing short-term employment needs of autistic people, but Medicaid was severely lacking-and losing ground-in serving those who need longer-term employment services. Across both Vocational Rehabilitation and Medicaid, we estimated that only 1.1% of working-age autistic adults who potentially need employment services are actually receiving them-leaving an estimated 1.98 million autistic individuals without the employment services that are associated with achievement of well-being. CONTEXT: Employment is a key social determinant of health. As such, high rates of unemployment, underemployment, and poverty across the rapidly growing autistic population are concerning. A web of publicly funded services exists to support the employment, and associated health and well-being, of United States citizens with autism and other intellectual and developmental disabilities, namely through Vocational Rehabilitation (VR) and Medicaid home- and community-based services (HCBS) waivers. Given an absence of overarching surveillance of employment services, this study aimed to characterize the distribution of autistic service users across Medicaid versus VR, understand the types of employment services utilized within these programs and expenditures, and assess overall capacity to provide employment services as needs continue to increase. METHODS: This study examined the distribution of employment services among autistic people compared with those with intellectual disability using 2008-2016 data from the Centers for Medicare & Medicaid Services and the Rehabilitation Services Administration. Estimated need for employment services among autistic individuals was compared with capacity derived from VR service counts and a review of HCBS waivers. FINDINGS: The number of autistic people served through VR tripled during the study years, whereas those served through Medicaid only increased slightly. VR spending increased by 384% over the study years, whereas Medicaid costs decreased by 29%. Across VR and Medicaid, we estimated that only 1.1% of working-age autistic adults who needed employment services received them. CONCLUSIONS: Although VR appeared to be absorbing short-term employment needs of autistic individuals, Medicaid was severely lacking-and losing ground-in serving those who needed longer-term employment services. VR far outpaced Medicaid in both the number of autistic people served and total expenditures across the study years. However, an estimated 1.98 million autistic adults did not receive employment services that could be critical to improving their health and well-being.

Motherhood and DREADD manipulation of the nucleus accumbens weaken established pair bonds in female prairie voles.

Monogamous pair bonding has evolved to enhance reproductive success and ensure offspring survival. Although the behavioral and neural mechanisms regulating the formation of pair bonds have been relatively well outlined, how these relationships are regulated and maintained across the lifetime of an individual remains relatively unexplored. One way to explore this is to study the maintenance of a social bond across a major life-history transition. The transition to motherhood is among the most poignant moments in the life history of a female, and is associated with significant neural and behavioral changes and shifting priorities. The nucleus accumbens (NAc) is known to modulate social valence and is central to mammalian pair bonding. In this study, we investigated two mechanisms driving variation in bond strength in the socially monogamous prairie vole (Microtus ochrogaster). We manipulated neural activity of the NAc at two distinct stages of life-history, before and after the birth of offspring, to assess how neural activity and social contexts modulate female pair bond strength. Our results showed DREADD (Designer Receptor Exclusively Activated by Designer Drugs) inhibition of the NAc decreases affiliative behavior towards the mating partner, whereas DREADD activation of the NAc increases affiliative behavior of strangers, thereby decreasing social selectivity. We also found a robust "birth effect" on pair bond strength, such that bonds with partners were weakened after the birth of offspring, an effect not attributable to the amount of cohabitation time with a partner. Overall, our data support the hypotheses that NAc activity modulates reward/saliency within the social brain in different ways, and that motherhood comes with a cost for the bond strength between mating partners.

Parental perspectives of outcomes following very preterm birth: Seeing the good, not just the bad.

AIM: To describe parental perspective on health and developmental outcomes of their preterm child in relation to level of neurodevelopmental impairment (NDI). METHODS: A parental survey about their children aged 15-36 months corrected age born ˂29 weeks' gestation investigated parental concerns and positive attributes. Parental responses in relation to their child's level of NDI were examined using Kruskal-Wallis and chi-square for trend tests. RESULTS: One hundred ninety-nine parental responses were obtained for 163 children, including 44% with NDI. Vast majority of parents reported their children were developing well with good physical health. All parents, irrespective of NDI, reported their children were happy and had a positive personality. Appreciation of social interactions was higher for parents of children without versus with NDI (96% vs. 87%, p = 0.039). Parents of children with NDI were more likely to express concerns than those without NDI. Overall, development was the most common area of concern (45%), followed by the child's future (40%) and physical health (35%). CONCLUSION: Parents of preterm children report many positive points and concerns, some of which are not examined in neonatal follow-up data. These parental perspectives could be used to inform parents of preterm infants, both antenatally and in the neonatal unit.

Experiences of Mothers of Preterm Infants in the Neonatal Intensive Care Unit During the COVID-19 Pandemic.

BACKGROUND: The neonatal intensive care unit (NICU) stay following the birth of a preterm infant can be stressful and traumatic for families. During the COVID-19 pandemic, the NICU environment changed precipitously as infection control and visitor restriction measures were implemented. PURPOSE: Our study aimed to examine the impact of the pandemic policies on the experiences of mothers of preterm infants during their stay in the NICU. METHODS: Semistructured interviews were conducted with mothers of preterm infants hospitalized in a Canadian tertiary-level NICU. Informed by interpretive description methodology, interview content was transcribed and analyzed using a thematic analysis approach. The identified themes were validated, clarified, or refined using investigator triangulation. RESULTS: Nine English-speaking mothers, aged 28 to 40 years, were interviewed. Four themes emerged from the analysis of their experiences: (1) disrupted family dynamic, support, and bonding; (2) physical and emotional isolation; (3) negative psychological impact compounded by added concerns, maternal role change, and survival mode mentality; and (4) positive aspects of the pandemic management measures. IMPLICATIONS FOR PRACTICE: During the pandemic, the way that care was provided in the NICU changed. This study helps to explore how neonatal clinicians can foster individual and organizational resilience to keep patients and families at the center of care, even when the healthcare system is under intense stress. IMPLICATIONS FOR RESEARCH: : Our results show that these changes heightened mothers' distress, but also had a modest positive impact. Further research about long-term consequences of pandemic policies on the mother and preterm infant after NICU discharge is warranted.

Identifying Graduation Rates and Practices in the U.S. Department of Housing and Urban Development-Veterans Affairs Supportive Housing Program.

Graduation from permanent supported housing program (PSH) is an important part of individuals' recovery and rehabilitation, yet little research has examined this process. We examined graduation rates, practices and policies in the U.S. Department of Veterans Affairs-Housing and Urban Development Supportive Housing (HUD-VASH) program, the largest PSH program in the United States. We used HUD-VASH administrative data from Fiscal Years 2016-2020 to summarize graduation rates from the program. Using a template analysis approach to open-ended online surveys from 65 HUD-VASH program managers, we identified key themes related to graduation practices. Graduations accounted for 21% of all HUD-VASH exits across all years. Graduation practices and policies varied across HUD-VASH programs, and staff expressed interest in having additional data to support graduation decisions. There may be value in developing standards for graduation criteria that is shared with clients and providers in supported housing programs in order to titrate care appropriately and support client independence.

Impact of Perinatal Exposure to SARS-CoV-2 Infection on Early Health Outcomes among Infants Born from 2020 to 2021 in British Columbia, Canada.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods: The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non-exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results: Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.

Lyme Disease, Anaplasmosis, and Babesiosis, Atlantic Canada.

In July 2021, a PCR-confirmed case of locally acquired Babesia microti infection was reported in Atlantic Canada. Clinical features were consistent with babesiosis and resolved after treatment. In a region where Lyme disease and anaplasmosis are endemic, the occurrence of babesiosis emphasizes the need to enhance surveillance of tickborne infections.

Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses.

BACKGROUND & AIMS: The colon is innervated by intrinsic and extrinsic neurons that coordinate functions necessary for digestive health. Sympathetic input suppresses colon motility by acting on intrinsic myenteric neurons, but the extent of sympathetic-induced changes on large-scale network activity in myenteric circuits has not been determined. Compounding the complexity of sympathetic function, there is evidence that sympathetic transmitters can regulate activity in non-neuronal cells (such as enteric glia and innate immune cells). METHODS: We performed anatomical tracing, immunohistochemistry, optogenetic (GCaMP calcium imaging, channelrhodopsin), and colon motility studies in mice and single-cell RNA sequencing in human colon to investigate how sympathetic postganglionic neurons modulate colon function. RESULTS: Individual neurons in each sympathetic prevertebral ganglion innervated the proximal or distal colon, with processes closely opposed to multiple cell types. Calcium imaging in semi-intact mouse colon preparations revealed changes in spontaneous and evoked neural activity, as well as activation of non-neuronal cells, induced by sympathetic nerve stimulation. The overall pattern of response to sympathetic stimulation was unique to the proximal or distal colon. Region-specific changes in cellular activity correlated with motility patterns produced by electrical and optogenetic stimulation of sympathetic pathways. Pharmacology experiments (mouse) and RNA sequencing (human) indicated that appropriate receptors were expressed on different cell types to account for the responses to sympathetic stimulation. Regional differences in expression of α-1 adrenoceptors in human colon emphasize the translational relevance of our mouse findings. CONCLUSIONS: Sympathetic neurons differentially regulate activity of neurons and non-neuronal cells in proximal and distal colon to promote distinct changes in motility patterns, likely reflecting the distinct roles played by these 2 regions.