Hydrophobic solution functions as a multifaceted mosquito repellent by enhancing chemical transfer, altering object tracking, and forming aversive memory.

Developing a safe and potent repellent of mosquitoes applicable to human skins is an effective measure against the spread of mosquito-borne diseases. Recently, we have identified that hydrophobic solutions such as low viscosity polydimethylsiloxane (L-PDMS) spread on a human skin prevent mosquitoes from staying on and biting it. This is likely due to the ability of L-PDMS in wetting mosquito legs and exerting a capillary force from which the mosquitoes attempt to escape. Here we show three additional functions of L-PDMS that can contribute to repel Aedes albopictus, by combining physicochemical analysis and behavioral assays in both an arm cage and a virtual flight arena. First, L-PDMS, when mixed with topical repellents and applied on a human skin, enhances the effect of topical repellents in reducing mosquito bites by efficiently transferring them to mosquito legs upon contact. Second, L-PDMS applied to mosquito tarsi compromises visual object tracking during flight, exerting an influence outlasting the contact. Finally, L-PDMS applied to mosquito tarsi acts as an aversive reinforcer in associative learning, making mosquitoes avoid the conditioned odor. These results uncover a multifaceted potential of L-PDMS in altering a sequence of mosquito behaviors from biting a human skin, visual object tracking following takeoff, to the response to an odor linked with L-PDMS.

Dopaminergic neurons dynamically update sensory values during olfactory maneuver.

Dopaminergic neurons (DANs) drive associative learning to update the value of sensory cues, but their contribution to the assessment of sensory values outside the context of association remains largely unexplored. Here, we show in Drosophila that DANs in the mushroom body encode the innate value of odors and constantly update the current value by inducing plasticity during olfactory maneuver. Our connectome-based network model linking all the way from the olfactory neurons to DANs reproduces the characteristics of DAN responses, proposing a concrete circuit mechanism for computation. Downstream of DANs, odors alone induce value- and dopamine-dependent changes in the activity of mushroom body output neurons, which store the current value of odors. Consistent with this neural plasticity, specific sets of DANs bidirectionally modulate flies' steering in a virtual olfactory environment. Thus, the DAN circuit known for discrete, associative learning also continuously updates odor values in a nonassociative manner.

Surfactants alter mosquito's flight and physical condition.

Mosquitoes carry lethal pathogens for humans and hundreds of thousands of people are killed by mosquito-borne diseases every year. Therefore, controlling mosquitoes is essential to protect the lives of people around the world. Insecticides are highly effective in controlling mosquitoes and have been used extensively worldwide. However, they have potentially harmful effects on biodiversity and environment, and some mosquitoes are resistant to insecticide ingredients and survive upon their application. Therefore, there is a demand for a method to control mosquitoes without using conventional insecticide ingredients. Here, we used Aedes albopictus to test whether solutions with low surface tension, particularly surfactant solutions can alter mosquito behavior by spreading over the hydrophobic cuticle of mosquitoes. We found that solutions with low surface tension indeed attached to mosquitoes flying or resting on the wall, and made them fall. In addition, solutions with yet lower surface tension covered the mosquito surface more quickly and widely, knocking down or killing mosquitoes. These results suggest that surfactants such as sodium dioctyl sulfosuccinate can be used to alter mosquito behavior without relying on conventional insecticides.

A Multi-regional Network Encoding Heading and Steering Maneuvers in Drosophila.

An internal sense of heading direction is computed from various cues, including steering maneuvers of the animal. Although neurons encoding heading and steering have been found in multiple brain regions, it is unclear whether and how they are organized into neural circuits. Here we show that, in flying Drosophila, heading and turning behaviors are encoded by population dynamics of specific cell types connecting the subregions of the central complex (CX), a brain structure implicated in navigation. Columnar neurons in the fan-shaped body (FB) of the CX exhibit circular dynamics that multiplex information about turning behavior and heading. These dynamics are coordinated with those in the ellipsoid body, another CX subregion containing a heading representation, although only FB neurons flip turn preference depending on the visual environment. Thus, the navigational system spans multiple subregions of the CX, where specific cell types show coordinated but distinct context-dependent dynamics.

Olfactory Landmark-Based Communication in Interacting Drosophila.

To communicate with conspecifics, animals deploy various strategies to release pheromones, chemical signals modulating social and sexual behaviors [1-5]. Importantly, a single pheromone induces different behaviors depending on the context and exposure dynamics [6-8]. Therefore, to comprehend the ethological role of pheromones, it is essential to characterize how neurons in the recipients respond to temporally and spatially fluctuating chemical signals emitted by donors during natural interactions. In Drosophila melanogaster, the male pheromone 11-cis-vaccenyl acetate (cVA) [9] activates specific olfactory receptor neurons (ORNs) [10, 11] to regulate diverse social and sexual behaviors in recipients [12-15]. Physicochemical analyses have identified this chemical on an animal's body [16, 17] and in its local environment [18, 19]. However, because these methods are imprecise in capturing spatiotemporal dynamics, it is poorly understood how individual pheromone cues are released, detected, and interpreted by recipients. Here, we developed a system based on bioluminescence to monitor neural activity in freely interacting Drosophila, and investigated the active detection and perception of the naturally emitted cVA. Unexpectedly, neurons specifically tuned to cVA did not exhibit significant activity during physical interactions between males, and instead responded strongly to olfactory landmarks deposited by males. These landmarks mediated attraction through Or67d receptors and allured both sexes to the marked region. Importantly, the landmarks remained attractive even when a pair of flies was engaged in courtship behavior. In contrast, female deposits did not affect the exploration pattern of either sex. Thus, Drosophila use pheromone marking to remotely signal their sexual identity and to enhance social interactions.

Decoding of Context-Dependent Olfactory Behavior in Drosophila.

Odor information is encoded in the activity of a population of glomeruli in the primary olfactory center. However, how this information is decoded in the brain remains elusive. Here, we address this question in Drosophila by combining neuronal imaging and tracking of innate behavioral responses. We find that the behavior is accurately predicted by a model summing normalized glomerular responses, in which each glomerulus contributes a specific, small amount to odor preference. This model is further supported by targeted manipulations of glomerular input, which biased the behavior. Additionally, we observe that relative odor preference changes and can even switch depending on the context, an effect correctly predicted by our normalization model. Our results indicate that olfactory information is decoded from the pooled activity of a glomerular repertoire and demonstrate the ability of the olfactory system to adapt to the statistics of its environment.

Overlapping MERS and mild AESD caused by HHV-6 infection.

We report the case of an overlapping encephalopathy syndrome consisting of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) caused by human herpesvirus-6. A previously healthy 17-month-old girl was admitted to our hospital as a precaution because of seizures that had developed more than 25 hours (h) after fever. Brain diffusion-weighted images (DWI) showed high signal intensity in the central splenial region on Day 2. She regained consciousness 16 h after the second seizure. On Day 6, she had a secondary cluster of partial seizures. DWI showed resolution of the splenial lesion and revealed reduced diffusion in the fronto-subcortical white matter. She regained consciousness 36 h after the secondary cluster of seizures without any sequelae. A third DWI performed on Day 15 showed that the fronto-subcortical white matter lesions had completely disappeared. Based on the clinicoradiological findings, we diagnosed the patient with overlapping MERS and mild AESD. Our case, together with previous reports, suggests that patients can develop combined encephalopathy syndromes as a phenotype. Many encephalopathy syndromes have been established and classified; however, some may not present as independent syndromes.

Pathway-specific utilization of synaptic zinc in the macaque ventral visual cortical areas.

Synaptic zinc is an activity-related neuromodulator, enriched in hippocampal mossy fibers and a subset of glutamatergic cortical projections, exclusive of thalamocortical or corticothalamic. Some degree of pathway specificity in the utilization of synaptic zinc has been reported in rodents. Here, we use focal injections of the retrograde tracer sodium selenite to identify zinc-positive (Zn+) projection neurons in the monkey ventral visual pathway. After injections in V1, V4, and TEO areas, neurons were detected preferentially in several feedback pathways but, unusually, were restricted to deeper layers without involvement of layers 2 or 3. Temporal injections resulted in more extensive labeling of both feedback and intratemporal association pathways. The Zn+ neurons had a broader laminar distribution, similar to results from standard retrograde tracers. After anterograde tracer injection in area posterior TE, electron microscopic analysis substantiated that a proportion of feedback synapses was co-labeled with zinc. Nearby injections, Zn+ intrinsic neurons concentrated in layer 2, but in temporal areas were also abundant in layer 6. These results indicate considerable pathway and laminar specificity as to which cortical neurons use synaptic zinc. Given the hypothesized roles of synaptic zinc, this is likely to result in distinct synaptic properties, possibly including differential synaptic plasticity within or across projections.

Confocal mapping of cortical inputs onto identified pyramidal neurons.

Using a confocal microscopy protocol, we carried out a microcircuitry investigation of cortical connections in monkey temporal cortex. Inputs were labeled by BDA injections in posterior area TE, and potential postsynaptic pyramidal neuron targets were labeled with EGFP, by injection of retrogradely transported adenovirus. We scored the number and distribution of putative contacts onto dendritic compartments of neurons in different layers. Initial results show that about 50 percent of apical dendrites of layer (L.) 6 neurons receive contacts, as they ascend through L.4 (n=1 brain), but only 30-35 percent of those from L.5 neurons (n=2). Basal dendrites of L.3 neurons also receive few contacts in L.4. This supports the role of layer 4 as an interlaminar relay in association cortex. In addition, our results indicate spatial heterogeneity in the occurrence and number of contacts, possibly due to subtype specificity in target preference. The maximum number of contacts, for a L.2 neuron projecting from anterior to posterior TE, was 29. This approach seems a useful alternative or complement to electron microscopic analyses of long distance connectivity.