Spectral cues are necessary to encode azimuthal auditory space in the mouse superior colliculus.

Sound localization plays a critical role in animal survival. Three cues can be used to compute sound direction: interaural timing differences (ITDs), interaural level differences (ILDs) and the direction-dependent spectral filtering by the head and pinnae (spectral cues). Little is known about how spectral cues contribute to the neural encoding of auditory space. Here we report on auditory space encoding in the mouse superior colliculus (SC). We show that the mouse SC contains neurons with spatially-restricted receptive fields (RFs) that form an azimuthal topographic map. We found that frontal RFs require spectral cues and lateral RFs require ILDs. The neurons with frontal RFs have frequency tunings that match the spectral structure of the specific head and pinna filter for sound coming from the front. These results demonstrate that patterned spectral cues in combination with ILDs give rise to the topographic map of azimuthal auditory space

Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits.

BackgroundThere are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function.ResultsWe morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types.ConclusionsTaken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation

Loss-of-function analysis of EphA receptors in retinotectal mapping

Peer reviewedPublisher PD

Good prospects: high-resolution telemetry data suggests novel brood site selection behaviour in waterfowl

Breeding success should increase with prior knowledge of the surrounding environment, which is dependent upon an animal\u27s ability to evaluate habitat. Prospecting for nesting locations and migratory stopover sites are well-established behaviours among bird species. We assessed whether three species of California dabbling ducks – mallards, Anas platyrhynchos, gadwall, Mareca strepera, and cinnamon teal, Spatula cyanoptera – in Suisun Marsh, California, U.S.A., a brackish marsh, prospect for suitable wetlands in the week prior to brooding. K-means cluster analyses grouped 29 mallard and gadwall hens into three groups. One group (N = 13) demonstrated evidence of brood site prospecting, with the fewest and latest prebrooding wetland visits. Of these hens, seven visited their future brood pond an average of 1.14 times and only shortly before brooding (1.29 days), obtaining current information on habitat suitability. For the remaining six hens, we did not detect a brooding wetland visit, possibly due to data limitations or because these hens acquired sufficient familiarity with the wetland habitat during nest breaks in adjacent wetlands, obviating the need to prospect the specific brood pond. The second identified group of hens (N = 11) visited the brooding wetland most frequently (on 4.55 days), further in advance (5.27 days), with the fewest unique wetland visits and the earliest brooding date (26 May). The final group of hens (N = 5) were the latest to brood (21 June) and visited the most wetlands, possibly due to less water or more broods present across the landscape. Brood ponds were always farther from the nest than the nearest ponds, indicating that habitat suitability or presence of conspecifics is more important to brood site selection. Prospecting provides hens with knowledge about current habitat conditions and allows them to ‘crowdsource’ public information regarding use of that habitat by other brooding hens. Prospecting may, therefore, benefit ducks inhabiting ephemeral habitats like those within Suisun Marsh, where brood habitat is limited and water cover changes rapidly during the breeding season

On the Importance of Countergradients for the Development of Retinotopy: Insights from a Generalised Gierer Model

During the development of the topographic map from vertebrate retina to superior colliculus (SC), EphA receptors are expressed in a gradient along the nasotemporal retinal axis. Their ligands, ephrin-As, are expressed in a gradient along the rostrocaudal axis of the SC. Countergradients of ephrin-As in the retina and EphAs in the SC are also expressed. Disruption of any of these gradients leads to mapping errors. Gierer's (1981) model, which uses well-matched pairs of gradients and countergradients to establish the mapping, can account for the formation of wild type maps, but not the double maps found in EphA knock-in experiments. I show that these maps can be explained by models, such as Gierer's (1983), which have gradients and no countergradients, together with a powerful compensatory mechanism that helps to distribute connections evenly over the target region. However, this type of model cannot explain mapping errors found when the countergradients are knocked out partially. I examine the relative importance of countergradients as against compensatory mechanisms by generalising Gierer's (1983) model so that the strength of compensation is adjustable. Either matching gradients and countergradients alone or poorly matching gradients and countergradients together with a strong compensatory mechanism are sufficient to establish an ordered mapping. With a weaker compensatory mechanism, gradients without countergradients lead to a poorer map, but the addition of countergradients improves the mapping. This model produces the double maps in simulated EphA knock-in experiments and a map consistent with the Math5 knock-out phenotype. Simulations of a set of phenotypes from the literature substantiate the finding that countergradients and compensation can be traded off against each other to give similar maps. I conclude that a successful model of retinotopy should contain countergradients and some form of compensation mechanism, but not in the strong form put forward by Gierer

Gold nanoparticles to improve HIV drug delivery

Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART

Accuracy of Using Visual Identification of White Sharks to Estimate Residency Patterns

Determining the residency of an aquatic species is important but challenging and it remains unclear what is the best sampling methodology. Photo-identification has been used extensively to estimate patterns of animals' residency and is arguably the most common approach, but it may not be the most effective approach in marine environments. To examine this, in 2005, we deployed acoustic transmitters on 22 white sharks (Carcharodon carcharias) in Mossel Bay, South Africa to quantify the probability of detecting these tagged sharks by photo-identification and different deployment strategies of acoustic telemetry equipment. Using the data collected by the different sampling approaches (detections from an acoustic listening station deployed under a chumming vessel versus those from visual sightings and photo-identification), we quantified the methodologies' probability of detection and determined if the sampling approaches, also including an acoustic telemetry array, produce comparable results for patterns of residency. Photo-identification had the lowest probability of detection and underestimated residency. The underestimation is driven by various factors primarily that acoustic telemetry monitors a large area and this reduces the occurrence of false negatives. Therefore, we propose that researchers need to use acoustic telemetry and also continue to develop new sampling approaches as photo-identification techniques are inadequate to determine residency. Using the methods presented in this paper will allow researchers to further refine sampling approaches that enable them to collect more accurate data that will result in better research and more informed management efforts and policy decisions

EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans

Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age

The Mouse Superior Colliculus: An Emerging Model for Studying Circuit Formation and Function

The superior colliculus (SC) is a midbrain area where visual, auditory and somatosensory information are integrated to initiate motor commands. The SC plays a central role in visual information processing in the mouse; it receives projections from 85% to 90% of the retinal ganglion cells (RGCs). While the mouse SC has been a long-standing model used to study retinotopic map formation, a number of technological advances in mouse molecular genetic techniques, large-scale physiological recordings and SC-dependent visual behavioral assays have made the mouse an even more ideal model to understand the relationship between circuitry and behavior