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Wolff GH, Lahondère C, Vinauger C, Rylance E, Riffell JA. 2023. “Neuromodulation and Differential Learning Across Mosquito Species .” Proc. R. Soc. B 290: 20222118.

Mosquitoes can learn to change their host-feeding behaviors, such as shifting activity times to avoid bednets or switching from biting animals to biting humans, leading to the transfer of zoonotic diseases. Dopamine is critical for insect learning, but its role in the antennal lobe remains unclear, and it is unknown whether different mosquito species learn the same odor cues. We assayed aversive olfactory learning and dopaminergic brain innervation in four mosquito species with different host preferences and report here that they differentially learn odors salient to their preferred host and innervation patterns vary across species. Using genetically-encoded GCaMP6s Aedes aegypti, we mapped odor-evoked antennal lobe activity and report that glomeruli tuned to 'learnable' odors have significantly higher dopaminergic innervation. Changes in dopamine expression in the antennal lobes of diverse invertebrate species may be an evolutionary mechanism to adapt olfactory learning circuitry without changing brain structure and for mosquitoes an ability to adapt to other hosts when their preferred are no longer present.

 Lahondère C, Vinauger C, Okubo RP, Wolff G, Akbari OS, Riffell JA. 2019. “The olfactory basis of orchid pollination by mosquitoes." PNAS, 

doi.org/10.1073/pnas.1910589117

Mosquitoes are important vectors of disease and require sources of carbohydrates for reproduction and survival. Unlike host-related behaviors of mosquitoes, comparatively less is understood about the mechanisms involved in nectar-feeding decisions, or how this sensory information is processed in the mosquito brain. Here we show that Aedes spp. mosquitoes, including Aedes aegypti, are effective visitors to the Platanthera obtusata orchid, and demonstrate this mutualism is mediated by the orchid’s scent and the balance of excitation and inhibition in the mosquito’s antennal lobe (AL). The P. obtusata orchid emits an attractive, nonanal-rich scent, whereas related Platantheraspecies – not visited by mosquitoes – emit scents dominated by lilac aldehyde. Calcium imaging experiments in the mosquito AL revealed that nonanal and lilac aldehyde each respectively activate the LC2 and AM2 glomerulus, and remarkably, the AM2 glomerulus is also sensitive to DEET, a mosquito repellent. Lateral inhibition between these two glomeruli corresponds to the level of attraction to the orchid scents: whereas the enriched nonanal scent of P. obtusata activates the LC2 and suppresses AM2, the high level of lilac aldehyde in the other orchid scents inverts this pattern of glomerular activity, and behavioral attraction is lost. These results demonstrate the ecological importance of mosquitoes beyond operating as disease vectors and open the door towards understanding the neural basis of mosquito nectar-seeking behaviors.

Thoen HH, Wolff GH, Marshall J, Sayre ME, Strausfeld NJ. 2019. “The Reniform Body: An Integrative Protocerebral Neuropil Complex of Stomatopods (Eumalacostraca) persisting in Brachyura.” J. Comp. Neurol., 528(7), 1079-1094.

Mantis shrimps (Stomatopoda) possess in common with other crustaceans, and with Hexapoda, specific neuroanatomical attributes of the protocerebrum, the most anterior part of the arthropod brain. These attributes include assemblages of interconnected centers called the central body complex and in the lateral protocerebra, situated in the eyestalks, paired mushroom bodies. The phenotypic homologues of these centers across Panarthropoda support the view that ancestral integrative circuits crucial to action selection and memory have persisted since the early Cambrian or late Ediacaran. However, the discovery of another prominent integrative neuropil in the stomatopod lateral protocerebrum raises the question whether it is unique to Stomatopoda or at least most developed in this lineage, which likely originated quite late in the upper Ordovician or early Devonian. Here we describe the neuroanatomical structure of this center, called the reniform body. Using confocal microscopy and classical silver staining, we demonstrate that the reniform body receives inputs from multiple sources, including the optic lobe’s lobula. Although the mushroom body also receives projections from the lobula, it is entirely distinct from the reniform body, albeit connected to it by discrete tracts. We discuss the implications of their co-existence in Stomatopoda, the This article is protected by copyright. All rights reserved. Accepted Article occurrence of the reniform body in another eumalacostracan lineage and what this may mean for our understanding of brain functionality in Pancrustacea.

Martín-Duran JM, Wolff GH, Strausfeld NJ, Hejnol A. 2016. “The larval nervous system of the penis worm Priapulus caudatus (Ecdysozoa).” Phil. Trans. R. Soc. B., 371: 20150050.

The origin and extreme diversification of the animal nervous system is a central question in biology. While most of the attention has traditionally been paid to those lineages with highly elaborated nervous systems (e.g. arthropods, vertebrates, annelids), only the study of the vast animal diversity can deliver a comprehensive view of the evolutionary history of this organ system. In this regard, the phylogenetic position and apparently conservative molecular, morphological and embryological features of priapulid worms (Priapulida) place this animal lineage as a key to understanding the evolution of the Ecdysozoa (i.e. arthropods and nematodes). In this study, we characterize the nervous system of the hatching larva and first lorica larva of the priapulid worm Priapulus caudatusby immunolabelling against acetylated and tyrosinated tubulin, pCaMKII, serotonin and FMRFamide. Our results show that a circumoral brain and an unpaired ventral nerve with a caudal ganglion characterize the central nervous system of hatching embryos. After the first moult, the larva attains some adult features: a neck ganglion, an introvert plexus, and conspicuous secondary longitudinal neurites. Our study delivers a neuroanatomical framework for future embryological studies in priapulid worms, and helps illuminate the course of nervous system evolution in the Ecdysozoa.

Wolff G, Harzsch S, Hansson B, Brown S, Strausfeld N. 2012. “Neuronal organization of the hemiellipsoid body of the land hermit crab Coenobita clypeatus: Correspondence with the mushroom body ground pattern.”  J. Comp. Neurol., 520:13, 2824-2846.

Malacostracan crustaceans and dicondylic insects possess large second-order olfactory neuropils called, respectively, hemiellipsoid bodies and mushroom bodies. Because these centers look very different in the two groups of arthropods, it has been debated whether these second-order sensory neuropils are homologous or whether they have evolved independently. Here we describe the results of neuroanatomical observations and experiments that resolve the neuronal organization of the hemiellipsoid body in the terrestrial Caribbean hermit crab, Coenobita clypeatus, and compare this organization with the mushroom body of an insect, the cockroach Periplaneta americana. Comparisons of the morphology, ultrastructure, and immunoreactivity of the hemiellipsoid body of C. clypeatus and the mushroom body of the cockroach P. americana reveal in both a layered motif provided by rectilinear arrangements of extrinsic and intrinsic neurons as well as a microglomerular organization. Furthermore, antibodies raised against DC0, the major catalytic subunit of protein kinase A, specifically label both the crustacean hemiellipsoid bodies and insect mushroom bodies. In crustaceans lacking eyestalks, where the entire brain is contained within the head, this antibody selectively labels hemiellipsoid bodies, the superior part of which approximates a mushroom body's calyx in having large numbers of microglomeruli. We propose that these multiple correspondences indicate homology of the crustacean hemiellipsoid body and insect mushroom body and discuss the implications of this with respect to the phylogenetic history of arthropods. We conclude that crustaceans, insects, and other groups of arthropods share an ancestral neuronal ground pattern that is specific to their second-order olfactory centers.

Strausfeld NJ, Wolff GH, Sayre ME. 2020. “Mushroom body homology and divergence across Pancrustacea.” eLIFE, 2020;9:e52411 doi: 10.7554/eLife.52411.

Descriptions of crustacean brains have focused mainly on three highly derived lineages of malacostracans: the reptantian infraorders represented by spiny lobsters, lobsters, and crayfish. Those descriptions advocate the view that dome- or cap-like neuropils, referred to as ‘hemiellipsoid bodies,’ are the ground pattern organization of centers that are comparable to insect mushroom bodies in processing olfactory information. Here we challenge the doctrine that hemiellipsoid bodies are a derived trait of crustaceans, whereas mushroom bodies are a derived trait of hexapods. We demonstrate that mushroom bodies typify lineages that arose before Reptantia and exist in Reptantia thereby indicating that the mushroom body, not the hemiellipsoid body, provides the ground pattern for both crustaceans and hexapods. We show that evolved variations of the mushroom body ground pattern are, in some lineages, defined by extreme diminution or loss and, in others, by the incorporation of mushroom body circuits into lobeless centers. Such transformations are ascribed to modifications of the columnar organization of mushroom body lobes that, as shown in Drosophila and other hexapods, contain networks essential for learning and memory.

Vinauger C, Lahondère C, Wolff GH, Locke LT, Liaw JE, Parrish JZ, Akbari OS, Dickinson MH, Riffell JA. 2018 “Modulation of host learning in Aedes aegypti mosquitoes.” Curr. Biol., 24:3, 333-344.e8.

How mosquitoes determine which individuals to bite has important epidemiological consequences. This choice is not random; most mosquitoes specialize in one or a few vertebrate host species, and some individuals in a host population are preferred over others. Mosquitoes will also blood feed from other hosts when their preferred is no longer abundant, but the mechanisms mediating these shifts between hosts, and heterogeneity for certain individuals within a host species, remain unclear. Here we show that olfactory learning may contribute to Aedes aegypti mosquito biting preferences and host shifts. Training and testing to scents of humans and other host species showed that mosquitoes can aversively learn the scent of specific humans and single odorants, and learn to avoid the scent of rats (but not chickens). Using pharmacological interventions, RNAi, and CRISPR gene editing, we found that modification of the Dopamine-1 receptor suppressed their learning abilities. We further show through combined electrophysiological and behavioural recordings from tethered flying mosquitoes that these odours evoke changes in both behaviour and antennal lobe (AL) neuronal responses, and that dopamine strongly modulates odour-evoked responses in AL neurons. Not only do these results provide direct experimental evidence that olfactory learning in mosquitoes can play an epidemiological role, but, collectively, they also provide neuroanatomical and functional demonstration of the role of dopamine in mediating this learning-induced plasticity, for the first time in a disease vector insect.

Wolff GH, Thoen HH, Marshall J, Sayre ME, Strausfeld NJ. 2017. “An insect-like mushroom body in a crustacean brain” eLife, 2017;6:e29889.

Mushroom bodies are the iconic learning and memory centers of insects. No previously described crustacean possesses a mushroom body as defined by strict morphological criteria although centers called hemiellipsoid bodies, which serve functions in sensory integration, have been viewed as evolutionarily convergent with mushroom bodies. Here we describe insect-like mushroom bodies in stomatopod malacostracan crustaceans (mantis shrimps), which more than any other crustacean taxon display sophisticated behaviors relating to predation, spatial memory, and visual recognition that match those of insects. However, neuroanatomical-based cladistics suggesting close phylogenetic proximity of insects and malacostracan crustaceans conflicts with genomic evidence showing hexapods closely related to simple crustaceans called remipedes. We show that unique neuronal identifiers provide key evidence demonstrating mushroom bodies in stomatopods that possess neural arrangements indistinguishable from those of the insect mushroom body. We discuss whether these corresponding phenotypes support an ancestral cerebral morphology of Pancrustacea or whether present evidence supports an extraordinary example of convergent evolution.

Wolff GH, Strausfeld NJ. 2016. “Genealogical correspondence of a forebrain centre implies an executive brain in the protostome-deuterostome bilaterian ancestor.” Phil. Trans. R. Soc. B., 371: 20150055.

Orthologous genes involved in the formation of proteins associated with memory acquisition are similarly expressed in forebrain centres that exhibit similar cognitive properties. These proteins include cAMP-dependent protein kinase A catalytic subunit (PKA-Ca) and phosphorylated Ca2+/calmodulindependent protein kinase II (pCaMKII), both required for long-term memory formation which is enriched in rodent hippocampus and insect mushroom bodies, both implicated in allocentric memory and both possessing corresponding neuronal architectures. Antibodies against these proteins resolve forebrain centres, or their equivalents, having the same ground pattern of neuronal organization in species across five phyla. The ground pattern is defined by olfactory or chemosensory afferents supplying systems of parallel fibres of intrinsic neurons intersected by orthogonal domains of afferent and efferent arborizations with local interneurons providing feedback loops. The totality of shared characters implies a deep origin in the protostome–deuterostome bilaterian ancestor of elements of a learning and memory circuit.

Proxies for such an ancestral taxon are simple extant bilaterians, particularly acoels that express PKA-Ca and pCaMKII in discrete anterior domains that can be properly referred to as brains.

Wolff GH, Strausfeld NJ. 2015. “Genealogical correspondence of mushroom bodies across invertebrate Phyla.” Curr. Biol., 25:1, 38-44.

Except in species that have undergone evolved loss, paired lobed centers referred to as ‘‘mushroom bodies’’ occur across invertebrate phyla. Unresolved is the question of whether these centers, which support learning and memory in insects, correspond genealogically or whether their neuronal organization suggests convergent evolution. Here, anatomical and immunohistological observations demonstrate that across phyla, mushroom body-like centers share a neuroanatomical ground pattern and proteins required for memory formation. Paired lobed or dome-like neuropils characterize the first brain segment (protocerebrum) of mandibulate and chelicerate arthropods and the nonganglionic brains of polychaete annelids, polyclad planarians, and nemerteans. Structural and cladistic analyses resolve an ancestral ground pattern common to all investigated

taxa: chemosensory afferents supplying thousands

of intrinsic neurons, the parallel processes of which establish orthogonal networks with feedback loops, modulatory inputs, and efferents. Shared ground patterns and their selective labeling with antisera against proteins required for normal mushroom body function in Drosophila are indicative of genealogical correspondence and thus an ancestral presence predating arthropod and lophotrochozoan origins. Implications of this are considered in the context of mushroom body function and early ecologies of

ancestral bilaterians.

Melo N, Wolff GH, Costa-da-Silva AL, Arribas R, Triana MF, Gugger M, Riffell JA, DeGennaro M, Stensmyr MC. 2019. “Geosmin attracts Aedes aegypti mosquitoes to oviposition sites.” Curr. Biol.,30(1), 127-134.

Geosmin is one of the most recognizable and common microbial smells on the planet. Some insects, like mosquitoes, require microbial-rich environments for their progeny, whereas for other insects such microbes may prove dangerous. In the vinegar fly Drosophila melanogaster, geosmin is decoded in a remarkably precise fashion and induces aversion, presumably signaling the presence of harmful microbes. We have here investigated the effect of geosmin on the behavior of the yellow fever mosquito Aedes aegypti. In contrast to flies, geosmin is not aversive in mosquitoes but stimulates egg-laying site selection. Female mosquitoes could associate geosmin with microbes, including cyanobacteria consumed by larvae, who also find geosmin – as well as geosmin producing cyanobacteria – attractive. Using in vivo multiphoton imaging from mosquitoes with pan-neural expression of the calcium reporter GCaMP6s, we show that Ae. aegypti code geosmin in a similar fashion to flies, i.e. with extreme sensitivity and with a high degree of selectivity. We further demonstrate that geosmin can be used as bait under field conditions, and finally we show that geosmin, which is both expensive and difficult to obtain, can be substituted by beetroot peel extract, providing a cheap and viable mean of mosquito control and surveillance in developing countries.​

Wolff GH, Riffell JA. 2018. “Olfaction, experience and neural mechanisms underlying mosquito host-preference.” J. Exp. Biol., 221: jeb157131 doi: 10.1242/jeb.157131.

Mosquitoes are best known for their proclivity towards biting humans and transmitting bloodborne pathogens, but there are over 3500 species, including both blood-feeding and non-blood-feeding taxa.  The diversity of host preference in mosquitoes is exemplified by the feeding habits of mosquitoes in the genus Malaya that feed on ant regurgitation or those from the genus Uranotaenia that favor amphibian hosts. Host preference is also by no means static, but is characterized by behavioral plasticity that allows mosquitoes to switch hosts when their preferred host is unavailable and by learning host cues associated with positive or negative experiences. Here we review the diverse range of host preference behaviors across the family Culicidae, which includes all mosquitoes and how adaptations in neural circuitry might affect changes in preference both within the life history of a mosquito and across evolutionary time-scales.

Thoen HH, Marshall J,  Wolff GH, Strausfeld NJ. 2017. “Insect-Like Organization of the Stomatopod Central Complex: Functional and Phylogenetic Implications.” Front. Behav. Neurosci., https://doi.org/10.3389/fnbeh.2017.00012.

One approach to investigating functional attributes of the central complex is to relate its various elaborations to pancrustacean phylogeny, to taxon-specific behavioral repertoires and ecological settings. Here we review morphological similarities between the central complex of stomatopod crustaceans and the central complex of dicondylic insects. We discuss whether their central complexes possess comparable functional properties, despite the phyletic distance separating these taxa, with mantis shrimp (Stomatopoda) belonging to the basal branch of Eumalacostraca. Stomatopods possess the most elaborate visual receptor system in nature and display a fascinating behavioral repertoire, including refined appendicular dexterity such as independently moving eyestalks. They are also unparalleled in their ability to maneuver during both swimming and substrate locomotion. Like other pancrustaceans, stomatopods possess a set of midline neuropils, called the central complex, which in dicondylic insects have been shown to mediate the selection of motor actions for a range of behaviors. As in dicondylic insects, the stomatopod central complex comprises a modular protocerebral bridge (PB) supplying decussating axons to a scalloped fan-shaped body (FB) and its accompanying ellipsoid body (EB), which is linked to a set of paired noduli and other recognized satellite regions. We consider the functional implications of these attributes in the context of stomatopod behaviors, particularly of their eyestalks that can move independently or conjointly depending on the visual scene.

Wolff GH, Strausfeld NJ. 2016. “The Insect Brain: A Commentated Primer.” Structure and Evolution of Invertebrate Nervous Systems. Eds. A. Schmidt-Rhaesa, S. Harzsch, G. Purschke. Oxford: Oxford University Press.

No consideration of the insect brain can escape its ancestry. This means the need to appreciate what parts of the brain specifically pertain to insects and what parts might have been present in their marine ancestors. (...)

 

Broad comparisons of brain organization across mandibulates demonstrate that insects and crustaceans are sister groups and that the organization of many of their neuropils and their constituent neurons correspond. (...) 

 

Following on from that observation, the remainder of this chapter will provide a condensed description – a primer of sorts – of the organization of a generic insect brain, largely synthesized from dipterous and blattoid species with a commentary on some of its most relevant functional attributes, with occasional comparisons with the brains of other arthropod taxa. For a description of the brains of insects in the context of their evolution and brain organization in other arthropod groups the reader is referred to a volume on arthropod neuroanatomy published by Harvard University Press (Strausfeld 2012).

Brown S, Wolff G. 2012. "Fine structural organization of the hemiellipsoid body of the land hermit crab Coenobita clypeatus."  J. Comp. Neurol., 520:13, 2847-2863.

Electron microscopical observations of the hemiellipsoid bodies of the land hermit crab Coenobita clypeatusresolve microglomerular synaptic complexes that are comparable to those observed in the calyces of insect mushroom bodies and which characterize olfactory inputs onto intrinsic neurons. In an adult hermit crab, intrinsic neurons and one class of efferent neurons originate from neuronal somata of globuli cells covering the hemiellipsoid bodies. Counts of their nucleoli show that about 120,000 globuli cells supply each hemiellipsoid body in an adult hermit crab. This number is comparable to the number of globuli cells supplying mushroom bodies of certain insects, such as honey bees and cockroaches. Counts of axons in tracts leading from the olfactory lobes to the hemiellipsoid bodies resolve 20,000 afferent axons, however, an order of magnitude greater than known for any insect. These afferent axons provide numerous swollen varicosities, each presynaptic to many small profiles, and thus comparable to the microglomeruli that characterize insect mushroom body calyces. Also, common to mushroom bodies and hemiellipsoid bodies are arrangements of intrinsic neurons, afferent neurons containing dense core vesicles, and systems of serial synaptic complexes that relate to postsynaptic profiles of efferent neurons. Together, the ultrastructural organization of the hemiellipsoid bodies of C. clypeatus supports the proposition that this center may share a common origin with the insect mushroom body despite obvious divergent evolution of overall shape.

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