Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Depth refuge and the impacts of SCUBA spearfishing on coral reef fishes

In recent decades, spearfishing with SCUBA has emerged as an efficient method for targeting reef fish in deeper waters. However, deeper waters are increasingly recognised as a potential source of refuge that may help sustain fishery resources. We used a combination of historical catch data over a 20-year time period and fishery-independent surveys to investigate the effects of SCUBA spearfishing on coral reef fish populations in the southern Mariana Islands. Two jurisdictions were studied; Guam, where SCUBA spearfishing is practiced, and the nearby Commonwealth of Northern Mariana Islands (CNMI), where SCUBA spearfishing has been banned since 2003. Fishery-independent data were collected using baited remote underwater stereo-video systems (stereo-BRUVs) stratified by depth, marine protected area status and jurisdiction. Herbivores (primary consumers) dominated spearfishing catches, with parrotfish (scarines) and surgeonfish/unicornfish (acanthurids) the main groups harvested. However, the large, endangered humphead wrasse (Cheilinus undulatus) was the main species by weight landed by SCUBA spearfishers. SCUBA spearfishing was associated with declining size of scarines over time and catches shifting from a dominance of large parrotfishes to a mixed assemblage with increasing proportions of acanthurids. Comparisons between Guam and the nearby CNMI revealed differences in the assemblage of fished species and also greater size of scarines and acanthurids in deep water where SCUBA fishing is banned. These results suggest that SCUBA spearfishing impacts reef fish populations and that the restriction of this fishing method will ensure refuge for fish populations in deeper waters. We recommend a ban on SCUBA spearfishing to preserve or aid the recovery of large, functionally important coral reef species and to improve the sustainability of coral reef fisheries

Lmo4 in the Basolateral Complex of the Amygdala Modulates Fear Learning

Pavlovian fear conditioning is an associative learning paradigm in which mice learn to associate a neutral conditioned stimulus with an aversive unconditioned stimulus. In this study, we demonstrate a novel role for the transcriptional regulator Lmo4 in fear learning. LMO4 is predominantly expressed in pyramidal projection neurons of the basolateral complex of the amygdala (BLC). Mice heterozygous for a genetrap insertion in the Lmo4 locus (Lmo4gt/+), which express 50% less Lmo4 than their wild type (WT) counterparts display enhanced freezing to both the context and the cue in which they received the aversive stimulus. Small-hairpin RNA-mediated knockdown of Lmo4 in the BLC, but not the dentate gyrus region of the hippocampus recapitulated this enhanced conditioning phenotype, suggesting an adult- and brain region-specific role for Lmo4 in fear learning. Immunohistochemical analyses revealed an increase in the number of c-Fos positive puncta in the BLC of Lmo4gt/+ mice in comparison to their WT counterparts after fear conditioning. Lastly, we measured anxiety-like behavior in Lmo4gt/+ mice and in mice with BLC-specific downregulation of Lmo4 using the elevated plus maze, open field, and light/dark box tests. Global or BLC-specific knockdown of Lmo4 did not significantly affect anxiety-like behavior. These results suggest a selective role for LMO4 in the BLC in modulating learned but not unlearned fear

A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder

Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments.

Del22q11 syndrome is caused by heterozygous deletion of an similar to3 Mb segment of chromosome 22q11.2. Children diagnosed with del22q11 syndrome commonly have learning difficulties, deficits of motor development, cognitive defects and attention deficit disorder. They also have a higher than normal risk for developing psychiatric disorders, mainly schizophrenia, schizoaffective disorder and bipolar disorder. Here, we show that mice that are heterozygously deleted for a subset of the genes that are deleted in patients have deficits in sensorimotor gating and learning and memory. The finding of sensorimotor gating deficits is particularly significant because patients with schizophrenia and schizotypal personality disorder show similar deficits. Thus, our deletion mouse models at least two major features of the del22q11-associated behavioral phenotype, and as such, represents an animal model of this complex behavioral phenotype. These findings not only open the way to pharmacological analyses that may lead to improved treatments, but also to the identification of gene/s that modulate these specific behaviors in humans

Reproductive movement, residency and fisheries vulnerability of brown-marbled grouper, Epinephelus fuscoguttatus (Forsskål, 1775)

The brown-marbled grouper, Epinephelus fuscoguttatus, is a long-lived, late-maturing protogynous species listed as Near Threatened by the IUCN. In Pohnpei, Micronesia, reproductively active brown-marbled grouper were tagged with acoustic and spaghetti-type tags at a multi-species fish spawning aggregation (FSA) site to establish patterns of movement, residency and seasonality. Telemetry confirmed the use of common reproductive migratory corridors and significant sex-specific variations in residency at the FSA. Combined underwater visual census and telemetry data verified a 3-month peak aggregation period, with aggregations forming and persisting over ca. 12 days prior to full moon between January and May. FSA formation coincided with seasonally low and relatively stable seawater temperatures. Some males frequented the FSA site during each aggregation month over two consecutive years. Conversely, most females were present at the FSA during only a single aggregation period, with the month of visitation consistent among years. Nearly two-thirds of tagged fish were relocated or recaptured within 11 km of the aggregation site, with a maximum detected distance of 26 km and a minimum estimated catchment area of 100–175 km2. Findings highlight the need for a combined approach to management that prohibits the capture and sale of reproductive adults and protects both spawning sites and common reproductive migratory corridors during aggregation periods

Isolation of 15 new polymorphic microsatellite markers from the blue-spine unicornfish Naso unicornis

The blue-spine unicornfish Naso unicornis is a widely distributed reef herbivore that is highly prized in\ud tropical Indo-Pacific fisheries. Appropriate management\ud for N. unicornis and other exploited reef fishes requires\ud detailed knowledge of larval migrant exchange between\ud isolated adult meta-populations and an understanding of\ud recruitment patterns at both local and larger geographic\ud scales. To this end, we have developed 15 microsatellite\ud loci to evaluate levels larval connectivity and detect\ud genetic patterns relevant to demographic processes in this\ud species. Microsatellites were isolated from total genomic\ud DNA using biotinylated probes and magnetic bead capture.\ud We screened these loci against 90 individuals sampled\ud from Guam in the tropical West Pacific. Loci contained\ud 5–23 alleles (mean = 15.7) and had a mean observed and\ud expected heterozygosity of 0.66 and 0.82, respectively.\ud One locus, which did not conform to the expectations of\ud Hardy–Weinberg equilibrium, is probably under selection.\ud Four others are probably confounded by the presence of\ud null alleles