Calmodulin modulates insect odorant receptor function

Insect odorant receptors (ORs) are heteromeric complexes of an odor-specific receptor protein (OrX) and a ubiquitous co-receptor protein (Orco). The ORs operate as non-selective cation channels, also conducting Ca²⁺ ions. The Orco protein contains a conserved putative calmodulin (CaM)-binding motif indicating a role of CaM in its function. Using Ca²⁺ imaging to monitor OR activity we investigated the effect of CaM inhibition on the function of OR proteins. Ca²⁺ responses elicited in Drosophila olfactory sensory neurons by stimulation with the synthetic OR agonist VUAA1 were reduced and prolonged by CaM inhibition with the potent antagonist W7 but not with the weak antagonist W5. A similar effect was observed for Orco proteins heterologously expressed in CHO cells when CaM was inhibited with W7, trifluoperazine or chlorpromazine, or upon overexpression of CaM-EF-hand mutants. With the Orco CaM mutant bearing a point mutation in the putative CaM site (K339N) the Ca²⁺ responses were akin to those obtained for wild type Orco in the presence of W7. There was no uniform effect of W7 on Ca²⁺ responses in CHO cells expressing complete ORs (Or22a/Orco, Or47a/Orco, Or33a/Orco, Or56a/Orco). For Or33a and Or47a we observed no significant effect of W7, while it caused a reduced response in cells expressing Or22a and a shortened response for Or56a.     

Neuronal assemblies: single cortical neurons are obedient members of a huge orchestra

Spontaneous cortical activity of single neurons is often either dismissed as noise, or is regarded as carrying no functional significance and hence is ignored. Our findings suggest that such concepts should be revised. We explored the coherent population activity of neuronal assemblies in primary sensory area in the absence of a sensory input. Recent advances in real-time optical imaging based on voltage-sensitive dyes (VSDI) have facilitated exploration of population activity and its intimate relationship to the activity of individual cortical neurons. It has been shown by in vivo intracellular recordings that the dye signal measures the sum of the membrane potential changes in all the neuronal elements in the imaged area, emphasizing subthreshold synaptic potentials and dendritic action potentials in neuronal arborizations originating from neurons in all cortical layers whose dendrites reach the superficial cortical layers. Thus, the VSDI has allowed us to image the rather illusive activity in neuronal dendrites that cannot be readily explored by single unit recordings. Surprisingly, we found that the amplitude of this type of ongoing subthreshold activity is of the same order of magnitude as evoked activity. We also found that this ongoing activity exhibited high synchronization over many millimeters of cortex. We then investigated the influence of ongoing activity on the evoked response, and showed that the two interact strongly. Furthermore, we found that cortical states that were previously associated only with evoked activity can actually be observed also in the absence of stimulation, for example, the cortical representation of a given orientation may appear without any visual input. This demonstration suggests that ongoing activity may also play a major role in other cortical function by providing a neuronal substrate for the dependence of sensory information processing on context, behavior, memory and other aspects of cognitive function.     

IFT52 plays an essential role in sensory cilia formation and neuronal sensory function in Drosophila

Cilia are microtubule-based, hair-like organelles involved in sensory function or motility, playing critical roles in many physiological processes such as reproduction, organ development, and sensory perception. In insects, cilia are restricted to certain sensory neurons and sperms, being important for chemical and mechanical sensing, and fertility. Although great progress has been made regarding the mechanism of cilia assembly, the formation of insect cilia remains poorly understand, even in the insect model organism Drosophila. Intraflagellar transport (IFT) is a cilia-specific complex that traffics protein cargos bidirectionally along the ciliary axoneme and is essential for most cilia. Here we investigated the role of IFT52, a core component of IFT-B, in cilia/flagellar formation in Drosophila. We show that Drosophila IFT52 is distributed along the sensory neuronal cilia, and is essential for sensory cilia formation. Deletion of Ift52 results in severe defects in cilia-related sensory behaviors. It should be noted that IFT52 is not detected in spermatocyte cilia or sperm flagella of Drosophila. Accordingly, ift52 mutants can produce sperms with normal motility, supporting a dispensable role of IFT in Drosophila sperm flagella formation. Altogether, IFT52 is a conserved protein essential for sensory cilia formation and sensory neuronal function in insects.     

The evolution of eye size in response to increased fish predation in Daphnia

Variation in eye size is ubiquitous across taxa. Increased eye size is correlated with improved vision and increased fitness via shifts in behavior. Tests of the drivers of eye size evolution have focused on macroevolutionary studies evaluating the importance of light availability. Predator‐induced mortality has recently been identified as a potential driver of eye size variation. Here, we tested the influence of increased predation by the fish predator, the alewife (Alosa pseudoharengus) on eye size evolution in waterfleas (Daphnia ambigua) from lakes in Connecticut. We quantified the relative eye size of Daphnia from lakes with and without alewife using wild‐caught and third‐generation laboratory reared specimens. This includes comparisons between lakes where alewife are present seasonally (anadromous) or permanently (landlocked). Wild‐caught specimens did not differ in eye size across all lakes. However, third‐generation lab reared Daphnia from lakes with alewife, irrespective of the form of alewife predation, exhibited significantly larger eyes than Daphnia from lakes without alewife. This genetically based increase in eye size may enhance the ability of Daphnia to detect predators. Alternatively, such shifts in eye size may be an indirect response to Daphnia aggregating at the bottom of lakes. To test these mechanisms, we collected Daphnia as a function of depth and found that eye size differed in Daphnia found at the surface versus the bottom of the water column between anadromous alewife and no alewife lakes. However, we found no evidence of Daphnia aggregating at the bottom of lakes. Such results indicate that the evolution of a larger eye may be explained by a connection between eyes and enhanced survival. We discuss the cause of the lack of concordance in eye size variation between our phenotypic and genetic specimens and the ultimate drivers of eye size.     

Selective inactivation of LGI1 in neuronal precursor cells leads to cortical dysplasia in mice

Constitutional mutations in Leucine‐rich glioma inactivated 1 (LGI1) predispose to an autosomal dominant epilepsy syndrome in humans and germline inactivation of LGI1 in mice leads to early onset seizures. LGI1 is highly expressed in the regions involved in neuronal stem cell generation and migration and detailed analysis of the brains in these mice reveals a subtle cortical dysplasia characterized by hypercellularity in the outer cortical layers. To investigate the cellular origin for this cortical dysplasia, we created mice that allow cell‐specific, conditional inactivation of LGI1. Exons 3–4, which contain critical motifs for LGI1 function, were targeted for deletion and, using a CMV‐cre mouse strain, global inactivation of LGI1 led to early onset seizures and the same cortical dysplasia seen in the constitutionally null mice. Similarly, inactivation of LGI1 in cells expressing Nestin, expressed primarily in neuronal precursor cells, led to early onset seizures and cortical dysplasia. In contrast, targeting inactivation of LGI1 in cells expressing Gfap, Camk2a, and parvalbumin, did not lead to cortical dysplasia. This strain of mouse, therefore, allows for a more refined investigation of the cell types involved in the cortical dysplasia seen following inactivation of LGI1 and potentially a better understanding of the molecular mechanisms behind LGI1‐induced epilepsy.     

Otolith shape lends support to the sensory drive hypothesis in rockfishes

The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures.     

Squares of different sizes: effect of geographical projection on model parameter estimates in species distribution modeling

In species distribution analyses, environmental predictors and distribution data for large spatial extents are often available in long‐lat format, such as degree raster grids. Long‐lat projections suffer from unequal cell sizes, as a degree of longitude decreases in length from approximately 110 km at the equator to 0 km at the poles. Here we investigate whether long‐lat and equal‐area projections yield similar model parameter estimates, or result in a consistent bias. We analyzed the environmental effects on the distribution of 12 ungulate species with a northern distribution, as models for these species should display the strongest effect of projectional distortion. Additionally we choose four species with entirely continental distributions to investigate the effect of incomplete cell coverage at the coast. We expected that including model weights proportional to the actual cell area should compensate for the observed bias in model coefficients, and similarly that using land coverage of a cell should decrease bias in species with coastal distribution. As anticipated, model coefficients were different between long‐lat and equal‐area projections. Having progressively smaller and a higher number of cells with increasing latitude influenced the importance of parameters in models, increased the sample size for the northernmost parts of species ranges, and reduced the subcell variability of those areas. However, this bias could be largely removed by weighting long‐lat cells by the area they cover, and marginally by correcting for land coverage. Overall we found little effect of using long‐lat rather than equal‐area projections in our analysis. The fitted relationship between environmental parameters and occurrence probability differed only very little between the two projection types. We still recommend using equal‐area projections to avoid possible bias. More importantly, our results suggest that the cell area and the proportion of a cell covered by land should be used as a weight when analyzing distribution of terrestrial species.     

“Sensory Switching” in Elbow Reconstruction

In the treatment of the soft tissue defect of the elbow, flap reconstruction is necessitated in many cases because of thinness of soft tissue at this region. In addition, reacquirement of tactile sensation is desirable because of the anatomical and specific functions of the elbow. Of three cases treated for elbow defects, one was reconstructed with a pedicled island forearm flap containing the lateral cutaneous nerve of the forearm, another was reconstructed with a venoneuro-accompanying artery fasciocutaneous flap (VNAF flap) containing the basilic vein, and the third with the VNAF flap containing the cephalic vein. The three cases demonstrated a sudden change of sensory territory 4 to 6 months after surgery, which was confirmed by touching the reconstructed region with patients'' eye-closed: from its original territory to the elbow in a “switching”-like action. Here we describe and discuss the concept of “sensory switching.”