Stimulus-selective lateral signaling between olfactory afferents enables parallel encoding of distinct CO₂ dynamics

An important problem in sensory processing is how lateral interactions that mediate the integration of information across sensory channels function with respect to their stimulus tunings. We demonstrate a novel form of stimulus-selective crosstalk between olfactory channels that occurs between primary olfactory receptor neurons (ORNs). Neurotransmitter release from ORNs can be driven by two distinct sources of excitation, feedforward activity derived from the odorant receptor and lateral input originating from specific subsets of other ORNs. Consequently, levels of presynaptic release can become dissociated from firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO₂, a behaviorally important environmental cue that elicits spiking in only a single ORN class, across multiple olfactory channels. Different CO₂-responsive channels preferentially transmit distinct stimulus dynamics, thereby expanding the coding bandwidth for CO₂. These results generalize to additional odors and olfactory channels, revealing a subnetwork of lateral interactions between ORNs that reshape the spatial and temporal structure of odor representations in a stimulus-specific manner

Stimulus-selective lateral signaling between olfactory afferents enables parallel encoding of distinct CO₂ dynamics

An important problem in sensory processing is how lateral interactions that mediate the integration of information across sensory channels function with respect to their stimulus tunings. We demonstrate a novel form of stimulus-selective crosstalk between olfactory channels that occurs between primary olfactory receptor neurons (ORNs). Neurotransmitter release from ORNs can be driven by two distinct sources of excitation, feedforward activity derived from the odorant receptor and lateral input originating from specific subsets of other ORNs. Consequently, levels of presynaptic release can become dissociated from firing rate. Stimulus-selective lateral signaling results in the distributed representation of CO₂, a behaviorally important environmental cue that elicits spiking in only a single ORN class, across multiple olfactory channels. Different CO₂-responsive channels preferentially transmit distinct stimulus dynamics, thereby expanding the coding bandwidth for CO₂. These results generalize to additional odors and olfactory channels, revealing a subnetwork of lateral interactions between ORNs that reshape the spatial and temporal structure of odor representations in a stimulus-specific manner

A reporter for amyloid precursor protein γ-secretase activity in Drosophila

A key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of senile plaques consisting largely of a peptide known as β-amyloid (Aβ) that is derived from the amyloid precursor protein (APP). A proteolytic activity called γ-secretase cleaves APP in the transmembrane domain and is required for Aβ generation. Aberrant γ-secretase cleavage of APP underlies the majority of early onset, familial AD. γ-Secretase resides in a large multi-protein complex, of which Presenilin, Nicastrin, APH-1 and PEN-2 are four essential components. Thus, identifying components and pathways by which the γ-secretase activity is regulated is crucial to understanding the mechanisms underlying AD pathogenesis, and may provide new diagnostic tools and therapeutic targets. Here we describe the generation of Drosophila that act as living reporters of γ-secretase activity in the fly eye. In these reporter flies the size of the eye correlates with the level of endogenous γ-secretase activity, and is very sensitive to the levels of three genes required for APP γ-secretase activity, presenilin, nicastrin and aph-1. Thus, these flies provide a sensitized system with which to identify other components of the γ-secretase complex and regulators of its activity. We have used these flies to carry out a screen for mutations that suppress γ-secretase activity and have identified a small chromosomal region that contains a gene or genes whose products may promote γ-secretase activity

Simultaneous Encoding of Odors by Channels with Diverse Sensitivity to Inhibition

Odorant receptors in the periphery map precisely onto olfactory glomeruli (“coding channels”) in the brain. However, the odor tuning of a glomerulus is not strongly correlated with its spatial position. This raises the question of whether lateral inhibition between glomeruli is specific or nonspecific. Here we show that, in the Drosophila brain, focal activation of even a single glomerulus recruits GABAergic interneurons in all glomeruli. Moreover, the relative level of interneuron activity in different glomeruli is largely odor invariant. Although interneurons are recruited nonspecifically, glomeruli differ dramatically in their sensitivity to interneuron activity, and this is explained by their varying sensitivity to GABA. Interestingly, a stimulus is typically encoded in parallel by channels having high and low sensitivity to inhibition. Because lateral inhibition confers both costs and benefits, the brain might rely preferentially on “high” and “low” channels in different behavioral contexts

Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy

Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolites that differed significantly between diet phases using metabolite fragmentation profiles generated by tandem MS (UPLC–MS/MS). Consumption of the MCTD resulted in significant differences in serum metabolic profiles when compared with the placebo diet, where sixteen altered lipid metabolites were identified. Consumption of the MCTD resulted in reduced abundances of palmitoylcarnitine, octadecenoylcarnitine, stearoylcarnitine and significant changes, both reduced and increased abundances, of phosphatidylcholine (PC) metabolites. There was a significant increase in abundance of the saturated C17 : 0 fatty acyl moieties during the MCTD phase. Lysophosphatidylcholine (17 : 0) (P=0·01) and PC (17:0/20:4) (P=0·03) were both significantly higher in abundance during the MCTD. The data presented in this study highlight global changes in lipid metabolism, and, of particular interest, in the C17 : 0 moieties, as a result of MCT consumption. Elucidating the global metabolic response of MCT consumption will not only improve the administration of current ketogenic diets for neurological disease models but also provides new avenues for research to develop better diet therapies with improved neuroprotective efficacies. Future studies should clarify the involvement and importance of C17 : 0 moieties in endogenous MCT metabolic pathways

General Sum Rules for WW Scattering in Higgsless Models: Equivalence Theorem and Deconstruction Identities

We analyze inelastic 2 to 2 scattering amplitudes for gauge bosons and Nambu-Goldstone bosons in deconstructed Higgsless models. Using the (KK) Equivalence Theorem in 4D (5D), we derive a set of general sum rules among the boson masses and multi-boson couplings that are valid for arbitrary deconstructed models. Taking the continuum limit, our results naturally include the 5D Higgsless model sum rules for arbitrary 5D geometry and boundary conditions; they also reduce to the elastic sum rules when applied to the special case of elastic scattering. For the case of linear deconstructed Higgsless models, we demonstrate that the sum rules can also be derived from a set of general deconstruction identities and completeness relations. We apply these sum rules to the deconstructed 3-site Higgsless model and its extensions; we show that in 5D ignoring all higher KK modes (n>1) is inconsistent once the inelastic channels become important. Finally, we discuss how our results generalize beyond the case of linear Higgsless models.Comment: 36 pages, 2 figure

Corneoscleral laceration and ocular burns caused by electronic cigarette explosions

PURPOSE: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. METHODS: Case series. RESULTS: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. CONCLUSIONS: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration

Brain-Derived Neurotrophic Factor Expression and Respiratory Function Improve after Ampakine Treatment in a Mouse Model of Rett Syndrome

Rett syndrome (RTT) is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Although MeCP2 is thought to act as a transcriptional repressor of brain-derived neurotrophic factor (BDNF), Mecp2 null mice, which develop an RTT-like phenotype, exhibit progressive deficits in BDNF expression. These deficits are particularly significant in the brainstem and nodose cranial sensory ganglia (NGs), structures critical for cardiorespiratory homeostasis, and may be linked to the severe respiratory abnormalities characteristic of RTT. Therefore, the present study used Mecp2 null mice to further define the role of MeCP2 in regulation of BDNF expression and neural function, focusing on NG neurons and respiratory control. We find that mutant neurons express significantly lower levels of BDNF than wild-type cells in vitro, as in vivo, under both depolarizing and nondepolarizing conditions. However, BDNF levels in mutant NG cells can be increased by chronic depolarization in vitro or by treatment of Mecp2 null mice with CX546, an ampakine drug that facilitates activation of glutamatergic AMPA receptors. Ampakine-treated Mecp2 null mice also exhibit marked functional improvement, characterized by restoration of normal breathing frequency and minute volume. These data demonstrate that BDNF expression remains plastic in Mecp2 null mice and raise the possibility that ampakine compounds could be of therapeutic value in the treatment of RTT

Deconstruction and Elastic pi pi Scattering in Higgsless Models

We study elastic pion-pion scattering in global linear moose models and apply the results to a variety of Higgsless models in flat and AdS space using the Equivalence Theorem. In order to connect the global moose to Higgsless models, we first introduce a block-spin transformation which corresponds, in the continuum, to the freedom to perform coordinate transformations in the Higgsless model. We show that it is possible to make an "f-flat" deconstruction in which all of the f-constants f_j of the linear moose model are identical; the phenomenologically relevant f-flat models are those in which the coupling constants of the groups at either end of the moose are small - corresponding to the global linear moose. In studying pion-pion scattering, we derive various sum rules, including one analogous to the KSRF relation, and use them in evaluating the low-energy and high-energy forms of the leading elastic partial wave scattering amplitudes. We obtain elastic unitarity bounds as a function of the mass of the lightest KK mode and discuss their physical significance.Comment: 33 pages, JHEP3. Minor typos correcte