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The acoustic startle reflex (ASR) and prepulse inhibition of the ASR (PPI) assess the efficiency of salience processing, a fundamental brain function that is impaired in many psychiatric conditions. Both ASR and PPI depend on noradrenergic transmission, yet the modulatory role of the locus coeruleus (LC) remains controversial. Clonidine (0.05 mg/kg, i.p.), an alpha2‐adrenoreceptor agonist, strongly reduced the ASR amplitude. In contrast, chemogenetic LC inhibition only mildly suppressed the ASR and did affect the PPI in virus‐transduced rats. The canine adenovirus type 2 (CAV2)–based vector carrying a gene cassette for the expression of inhibitory receptors (hM4Di) and noradrenergic cell–specific promoter (PRSx8) had high cell‐type specificity (94.4 ± 3.1%) but resulted in heterogeneous virus transduction of DbH‐positive LC neurons (range: 9.2–94.4%). Clozapine‐N‐oxide (CNO; 1 mg/kg, i.p.), a hM4Di actuator, caused the firing cessation of hM4Di‐expressing LC neurons, yet complete inhibition of the entire population of LC neurons was not achieved. Case‐based immunohistochemistry revealed that virus injections distal (> 150 μm) to the LC core resulted in partial LC transduction, while proximal (< 50 μm) injections caused neuronal loss due to virus neurotoxicity. Neither the ASR nor PPI differed between the intact and virus‐transduced rats. Our results suggest that a residual activity of virus‐non‐transduced LC neurons might have been sufficient for mediating an unaltered ASR and PPI. Our study highlights the importance of a case‐based assessment of the virus efficiency, specificity, and neurotoxicity for targeted cell populations and of considering these factors when interpreting behavioral effects in experiments employing chemogenetic modulation. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)‐2 vaccinations and assessed the utility of CAV‐1 and CAV‐2 titers in elucidation of its etiopathogenesis. Animals studied: Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs. Procedures: The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age‐matched dogs without corneal edema but with CAV titers were included as controls. Results: Mean CAV‐1 and CAV‐2 titers were not statistically different between dogs with keratouveitis and controls (p =.16 and p =.76, respectively). Three cases had CAV‐1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11‐fold increase) suggesting infection with wild‐type CAV‐1. The six other cases did not appear to be associated with CAV infection or vaccination. Conclusion: Keratouveitis continues to occur despite the advent of CAV‐2 vaccinations. While this study found no evidence to indicate CAV‐2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild‐type CAV‐1 infection is a possible cause. [ABSTRACT FROM AUTHOR]

Domestic animal populations have the potential to act as reservoirs for multi-host pathogens, which may be transmitted to native species and cause population declines or extirpations. Domestic dogs are known reservoirs for several multi-host pathogens that may be transmitted to native carnivores. Mass vaccination of dogs has been suggested as a tool for mitigating the disease threat to sympatric carnivores. To determine the extent to which such mass vaccination programs are practicable and appropriate for large, free-ranging dog populations, a vaccination experiment was undertaken in six villages adjoining the Great Indian Bustard Wildlife Sanctuary in central India. Dogs from three villages were vaccinated against rabies virus, canine adenovirus ( CAV), canine parvovirus ( CPV) and canine distemper virus ( CDV) (treatment dogs), while those from three other villages were only vaccinated against rabies virus (control dogs). Immunoglobulin G ( IgG) antibody titers against CAV, CPV and CDV in control and treatment dogs were determined on four occasions during the study. When first examined, a large proportion of the initially unvaccinated adult dogs in both the control and treatment group were IgG antibody positive, indicating prior natural exposure. Dogs recovering from natural infection because of CAV, CPV and CDV develop a lifelong immunity and are thus protected against these pathogens. For each of the three viruses, background antibody seroprevalence rates were generally > 72%. Furthermore, several unvaccinated adult dogs acquired protection against these pathogens during the study. Vaccination failed to increase the proportion of adult dogs with IgG antibodies against CAV, CPV or CDV in the treatment group compared with the control group, as much of the effort was put into vaccinating dogs that were already antibody positive. In such situations, vaccination of adult dogs against these enzootic viral pathogens seems unnecessary, and would escalate the cost-benefit ratio of dog disease control programs. [ABSTRACT FROM AUTHOR]

There is an increasing concern that free-ranging domestic dog ( Canis familiaris) populations may serve as reservoirs of pathogens which may be transmitted to wildlife. We documented the prevalence of antibodies to three viral pathogens, canine parvovirus ( CPV), canine distemper virus ( CDV) and canine adenovirus ( CAV), in free-ranging dog and sympatric Indian fox ( Vulpes bengalensis) populations in and around the Great Indian Bustard Wildlife Sanctuary, in Maharashtra, central India. A total of 219 dogs and 33 foxes were sampled during the study period. Ninety-three percentage of dogs and 87% of foxes were exposed to one or more of the three pathogens. Exposure rates in dogs were high: >88% for CPV, >72% for CDV and 71% for CAV. A large proportion of adult dogs had antibodies against these pathogens due to seroconversion following earlier natural infection. The high prevalence of exposure to these pathogens across the sampling sessions, significantly higher exposure rates of adults compared with juveniles, and seroconversion in some unvaccinated dogs documented during the study period suggests that these pathogens are enzootic. The prevalence of exposure to CPV, CDV and CAV in foxes was 48%, 18% and 52%, respectively. Further, a high rate of mortality was documented in foxes with serologic evidence of ongoing CDV infection. Dogs could be playing a role in the maintenance and transmission of these pathogens in the fox population, but our findings show that most dogs in the population are immune to these pathogens by virtue of earlier natural infection, and therefore, these individuals make little current or future contribution to viral maintenance. Vaccination of this cohort will neither greatly improve their collective immune status nor contribute to herd immunity. Our findings have potentially important implications for dog disease control programmes that propose using canine vaccination as a tool for conservation management of wild carnivore populations. [ABSTRACT FROM AUTHOR]

Complexity in the nervous system is established by developmental genetic programs, maintained by differential genetic profiles and sculpted by experiential and environmental influence over gene expression. Determining how specific genes define neuronal phenotypes, shape circuit connectivity and regulate circuit function is essential for understanding how the brain processes information, directs behavior and adapts to changing environments. Mouse genetics has contributed greatly to current percepts of gene-circuit interfaces in behavior, but considerable work remains. Large-scale initiatives to map gene expression and connectivity in the brain, together with advanced techniques in molecular genetics, now allow detailed exploration of the genetic basis of nervous system function at the level of specific circuit connections. In this review, we highlight several key advances for defining the function of specific genes within a neural network. [ABSTRACT FROM AUTHOR]