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How do neural circuits accommodate changes that produce cognitive variation? We explore this question by analyzing the evolutionary dynamics of an insect learning and memory circuit centered within the mushroom body. Mushroom bodies are composed of a conserved wiring logic, mainly consisting of Kenyon cells, dopaminergic neurons, and mushroom body output neurons. Despite this conserved makeup, there is huge diversity in mushroom body size and shape across insects. However, empirical data on how evolution modifies the function and architecture of this circuit are largely lacking. To address this, we leverage the recent radiation of a Neotropical tribe of butterflies, the Heliconiini (Nymphalidae), which show extensive variation in mushroom body size over comparatively short phylogenetic timescales, linked to specific changes in foraging ecology, life history, and cognition. To understand how such an extensive increase in size is accommodated through changes in lobe circuit architecture, we combined immunostainings of structural markers, neurotransmitters, and neural injections to generate new, quantitative anatomies of the Nymphalid mushroom body lobe. Our comparative analyses across Heliconiini demonstrate that some Kenyon cell sub-populations expanded at higher rates than others in Heliconius and identify an additional increase in GABA-ergic feedback neurons, which are essential for non-elemental learning and sparse coding. Taken together, our results demonstrate mosaic evolution of functionally related neural systems and cell types and identify that evolutionary malleability in an architecturally conserved parallel circuit guides adaptation in cognitive ability. [Display omitted] • Heliconiini butterflies have conserved wiring logic in spheroid mushroom body lobes • Kenyon cell populations expanded to differing degrees in Heliconius butterflies • Increased numbers of feedback neurons and conservation in dopaminergic neurons • Mosaic evolution to facilitate cognitive processes associated with pollen feeding Farnworth et al. use anatomical and statistical means to examine how the internal circuitry of the mushroom bodies changed coincidently with a major increase in their volume in Heliconius butterflies. They reveal that specific Kenyon cell populations expanded to differing degrees and that associated cell groups show diverging patterns of change. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) of Chelicerata has remained conserved since the Cambrian, yet few studies have examined its variability within chelicerate orders including Scorpiones. The scorpion CNS comprises the prosomal ganglion and opisthosomal ventral nerve cord. We visualize the scorpion CNS with microCT, explore morphological variation across taxa, compare the scorpion CNS to other arachnids, and create a terminology glossary and literature review to assist future studies. Six scorpion species were microCT scanned. Scan quality varied and most structures in the prosomal ganglion could only be observed in Paruroctonus becki (Vaejovidae). Major nerves and the first opisthosomal ganglion were visible in nearly all taxa. We present the most detailed 3D-rendering of the scorpion prosomal ganglion to date. Our results corroborate existing research and find the scorpion CNS to be conserved. Nearly all structures reported previously in the prosomal ganglion were located in similar positions in P. becki, and nerve morphology was conserved across examined families. Despite similarities, we report differences from the literature, observe taxonomic variation in prosomal ganglion shape, and confirm positional variation for the first opisthosomal ganglion. This study serves as a starting point for microCT analysis of the scorpion CNS, and future work should include more distantly related, size variable taxa to better elucidate these findings. [ABSTRACT FROM AUTHOR]

Abstract The central nervous system (CNS) of Chelicerata has remained conserved since the Cambrian, yet few studies have examined its variability within chelicerate orders including Scorpiones. The scorpion CNS comprises the prosomal ganglion and opisthosomal ventral nerve cord. We visualize the scorpion CNS with microCT, explore morphological variation across taxa, compare the scorpion CNS to other arachnids, and create a terminology glossary and literature review to assist future studies. Six scorpion species were microCT scanned. Scan quality varied and most structures in the prosomal ganglion could only be observed in Paruroctonus becki (Vaejovidae). Major nerves and the first opisthosomal ganglion were visible in nearly all taxa. We present the most detailed 3D-rendering of the scorpion prosomal ganglion to date. Our results corroborate existing research and find the scorpion CNS to be conserved. Nearly all structures reported previously in the prosomal ganglion were located in similar positions in P. becki, and nerve morphology was conserved across examined families. Despite similarities, we report differences from the literature, observe taxonomic variation in prosomal ganglion shape, and confirm positional variation for the first opisthosomal ganglion. This study serves as a starting point for microCT analysis of the scorpion CNS, and future work should include more distantly related, size variable taxa to better elucidate these findings.

Bisphenol AP (BPAP), an environmental endocrine disruptor, may cause neurodevelopmental disorders affecting human health. Studies have shown that BPAP impacts hormone synthesis and metabolism, causes social behavior abnormalities, and induces anxiety-like behavioral impairments in mice. However, evidence for the neurobehavioral effects of BPAP is still lacking. Here, we examined the toxic effects of BPAP on neurodevelopment using a Drosophila model. We assessed the role of BPAP exposure in autism-like behavior and explored the underlying mechanisms. Our findings indicated that BPAP exposure reduced pupation and eclosion rates and delayed growth in Drosophila. Furthermore, BPAP exposure caused autism-like behaviors, characterized by increased grooming times and aberrant social interactions, along with abnormalities in locomotor activity, as well as learning and memory ability. Mechanistically, we found that BPAP decreases the number of neuroblasts (NBs) and mature intermediate neural progenitors (INPs) in the 3rd larval brain, impairing axon guidance in the mushroom body of the adult Drosophila brain. Additionally, our transcriptome analysis revealed that BPAP exposure alters the expression of neurodevelopment-related genes (Nplp3, sand, lush, and orco) and affects the estrogen signaling pathway (Hsp70Ab, Hsp70Bc, Hsp70Ba, and Hsp70Bb). These changes potentially explain the BPAP-induced autism-like behavior in Drosophila.

Ants are capable of learning long visually guided foraging routes with limited neural resources. The visual scene memory needed for this behaviour is mediated by the mushroom bodies; an insect brain region important for learning and memory. In a visual navigation context, the mushroom bodies are theorised to act as familiarity detectors, guiding ants to views that are similar to those previously learned when first travelling along a foraging route. Evidence from behavioural experiments, computational studies and brain lesions all support this idea. Here we further investigate the role of mushroom bodies in visual navigation with a spiking neural network model learning complex natural scenes. By implementing these networks in GeNN-a library for building GPU accelerated spiking neural networks-we were able to test these models offline on an image database representing navigation through a complex outdoor natural environment, and also online embodied on a robot. The mushroom body model successfully learnt a large series of visual scenes (400 scenes corresponding to a 27 m route) and used these memories to choose accurate heading directions during route recapitulation in both complex environments. Through analysing our model's Kenyon cell (KC) activity, we were able to demonstrate that KC activity is directly related to the respective novelty of input images. Through conducting a parameter search we found that there is a non-linear dependence between optimal KC to visual projection neuron (VPN) connection sparsity and the length of time the model is presented with an image stimulus. The parameter search also showed training the model on lower proportions of a route generally produced better accuracy when testing on the entire route. We embodied the mushroom body model and comparator visual navigation algorithms on a Quanser Q-car robot with all processing running on an Nvidia Jetson TX2. On a 6.5 m route, the mushroom body model had a mean distance to training route (error) of 0.144 ±0.088 m over 5 trials, which was performance comparable to standard visual-only navigation algorithms. Thus, we have demonstrated that a biologically plausible model of the ant mushroom body can navigate complex environments both in simulation and the real world. Understanding the neural basis of this behaviour will provide insight into how neural circuits are tuned to rapidly learn behaviourally relevant information from complex environments and provide inspiration for creating bio-mimetic computer/robotic systems that can learn rapidly with low energy requirements. [ABSTRACT FROM AUTHOR]

Activation of the cAMP pathway is one of the common mechanisms underlying long‐term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour‐coding Kenyon cells (KCs) and reinforcement‐coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long‐term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we developed a system to electrophysiologically monitor both short‐term and long‐term synaptic plasticity at KC output synapses and demonstrated that they are indeed an exception in which activation of the cAMP–protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging found no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we found that forskolin‐induced cAMP increase alone was insufficient for plasticity induction; it additionally required simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induced slowly developing LTP, proving antagonistic actions of the two second‐messenger pathways predicted by behavioural study. Finally, KC subtype‐specific interrogation of synapses revealed that different KC subtypes exhibit distinct plasticity duration even among synapses on the same postsynaptic neuron. Thus, our work not only revises the role of cAMP in synaptic plasticity by uncovering the unexpected convergence point of the cAMP pathway and neuronal activity, but also establishes the methods to address physiological mechanisms of synaptic plasticity in this important model. Key points: Although presynaptic cAMP increase generally facilitates synapses, olfactory associative learning in Drosophila, which depends on dopamine and cAMP signalling genes, induces long‐term depression (LTD) at the mushroom body output synapses.By combining electrophysiology, pharmacology and optogenetics, we directly demonstrate that these synapses are an exception where activation of the cAMP–protein kinase A pathway leads to presynaptic LTD.Dopamine‐ or forskolin‐induced cAMP increase alone is not sufficient for LTD induction; neuronal activity, which has been believed to trigger cAMP synthesis in synergy with dopamine input, is required in the downstream pathway of cAMP.In contrast to cAMP, activation of the cGMP pathway paired with neuronal activity induces presynaptic long‐term potentiation, which explains behaviourally observed opposing actions of transmitters co‐released by dopaminergic neurons.Our work not only revises the role of cAMP in synaptic plasticity, but also provides essential methods to address physiological mechanisms of synaptic plasticity in this important model system. [ABSTRACT FROM AUTHOR]

Relevance-based selectivity and high energy cost are two distinct features of long-term memory (LTM) formation that warrant its default inhibition. Spaced repetition of learning is a highly conserved cognitive mechanism that can lift this inhibition. Here, we questioned how the spacing effect integrates experience selection and energy efficiency at the cellular and molecular levels. We showed in Drosophila that spaced training triggers LTM formation by extending over several hours an increased mitochondrial metabolic activity in neurons of the associative memory center, the mushroom bodies (MBs). We found that this effect is mediated by PKCδ, a member of the so-called ‘novel PKC’ family of enzymes, which uncovers the critical function of PKCδ in neurons as a regulator of mitochondrial metabolism for LTM. Additionally, PKCδ activation and translocation to mitochondria result from LTM-specific dopamine signaling on MB neurons. By bridging experience-dependent neuronal circuit activity with metabolic modulation of memory-encoding neurons, PKCδ signaling binds the cognitive and metabolic constraints underlying LTM formation into a unified gating mechanism.

Aging is associated with cognitive decline, which can critically affect quality of life. Examining the biology of cognitive aging across species will lead to a better understanding of the fundamental mechanisms involved in this process, and identify potential interventions that could help to improve cognitive function in aging individuals. This minireview aimed to explore the mechanisms and processes involved in cognitive aging across a range of species, from flies to rodents, and covers topics, such as the role of reactive oxygen species and autophagy/mitophagy in cognitive aging. Overall, this literature provides a comprehensive overview of the biology of cognitive aging across species, highlighting the latest research findings and identifying potential avenues for future research. Geriatr Gerontol Int 2024; 24: 15–24. [ABSTRACT FROM AUTHOR]

Ants are capable of learning long visually guided foraging routes with limited neural resources. The visual scene memory needed for this behaviour is mediated by the mushroom bodies; an insect brain region important for learning and memory. In a visual navigation context, the mushroom bodies are theorised to act as familiarity detectors, guiding ants to views that are similar to those previously learned when first travelling along a foraging route. Evidence from behavioural experiments, computational studies and brain lesions all support this idea. Here we further investigate the role of mushroom bodies in visual navigation with a spiking neural network model learning complex natural scenes. By implementing these networks in GeNN–a library for building GPU accelerated spiking neural networks–we were able to test these models offline on an image database representing navigation through a complex outdoor natural environment, and also online embodied on a robot. The mushroom body model successfully learnt a large series of visual scenes (400 scenes corresponding to a 27 m route) and used these memories to choose accurate heading directions during route recapitulation in both complex environments. Through analysing our model’s Kenyon cell (KC) activity, we were able to demonstrate that KC activity is directly related to the respective novelty of input images. Through conducting a parameter search we found that there is a non-linear dependence between optimal KC to visual projection neuron (VPN) connection sparsity and the length of time the model is presented with an image stimulus. The parameter search also showed training the model on lower proportions of a route generally produced better accuracy when testing on the entire route. We embodied the mushroom body model and comparator visual navigation algorithms on a Quanser Q-car robot with all processing running on an Nvidia Jetson TX2. On a 6.5 m route, the mushroom body model had a mean distance to training route (error) of 0.144 ± 0.088 m over 5 trials, which was performance comparable to standard visual-only navigation algorithms. Thus, we have demonstrated that a biologically plausible model of the ant mushroom body can navigate complex environments both in simulation and the real world. Understanding the neural basis of this behaviour will provide insight into how neural circuits are tuned to rapidly learn behaviourally relevant information from complex environments and provide inspiration for creating bio-mimetic computer/robotic systems that can learn rapidly with low energy requirements.

Abstract Background Dysregulation of nucleocytoplasmic shuttling of histone deacetylase 4 (HDAC4) is associated with several neurodevelopmental and neurodegenerative disorders. Consequently, understanding the roles of nuclear and cytoplasmic HDAC4 along with the mechanisms that regulate nuclear entry and exit is an area of concerted effort. Efficient nuclear entry is dependent on binding of the transcription factor MEF2, as mutations in the MEF2 binding region result in cytoplasmic accumulation of HDAC4. It is well established that nuclear exit and cytoplasmic retention are dependent on 14–3-3-binding, and mutations that affect binding are widely used to induce nuclear accumulation of HDAC4. While regulation of HDAC4 shuttling is clearly important, there is a gap in understanding of how the nuclear and cytoplasmic distribution of HDAC4 impacts its function. Furthermore, it is unclear whether other features of the protein including the catalytic site, the MEF2-binding region and/or the ankyrin repeat binding motif influence the distribution and/or activity of HDAC4 in neurons. Since HDAC4 functions are conserved in Drosophila, and increased nuclear accumulation of HDAC4 also results in impaired neurodevelopment, we used Drosophila as a genetic model for investigation of HDAC4 function. Results Here we have generated a series of mutants for functional dissection of HDAC4 via in-depth examination of the resulting subcellular distribution and nuclear aggregation, and correlate these with developmental phenotypes resulting from their expression in well-established models of neuronal morphogenesis of the Drosophila mushroom body and eye. We found that in the mushroom body, forced sequestration of HDAC4 in the nucleus or the cytoplasm resulted in defects in axon morphogenesis. The actions of HDAC4 that resulted in impaired development were dependent on the MEF2 binding region, modulated by the ankyrin repeat binding motif, and largely independent of an intact catalytic site. In contrast, disruption to eye development was largely independent of MEF2 binding but mutation of the catalytic site significantly reduced the phenotype, indicating that HDAC4 acts in a neuronal-subtype-specific manner. Conclusions We found that the impairments to mushroom body and eye development resulting from nuclear accumulation of HDAC4 were exacerbated by mutation of the ankyrin repeat binding motif, whereas there was a differing requirement for the MEF2 binding site and an intact catalytic site. It will be of importance to determine the binding partners of HDAC4 in nuclear aggregates and in the cytoplasm of these tissues to further understand its mechanisms of action.

O-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived from Clostridium perfringens OGA (CpOGA) with TurboID proximity labeling in Drosophila, we developed an O-GlcNAcylation profiling tool that translates O-GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the O-GlcNAc interactome in major brain regions of Drosophila and found that components of the translational machinery, particularly ribosomal subunits, were abundantly O-GlcNAcylated in the mushroom body of Drosophila brain. Hypo-O-GlcNAcylation induced by ectopic expression of active CpOGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of O-GlcNAcylation in Drosophila, and suggests a possibility that O-GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.

In well-established first-order conditioning experiments, the concurrence of a sensory cue with reinforcement forms an association, allowing the cue to predict future reinforcement. In the insect mushroom body, a brain region central to learning and memory, such associations are encoded in the synapses between its intrinsic and output neurons. This process is mediated by the activity of dopaminergic neurons that encode reinforcement signals. In second-order conditioning, a new sensory cue is paired with an already established one that presumably activates dopaminergic neurons due to its predictive power of the reinforcement. We explored minimal circuit motifs in the mushroom body for their ability to support second-order conditioning using mechanistic models. We found that dopaminergic neurons can either be activated directly by the mushroom body’s intrinsic neurons or via feedback from the output neurons via several pathways. We demonstrated that the circuit motifs differ in their computational efficiency and robustness. Beyond previous research, we suggest an additional motif that relies on feedforward input of the mushroom body intrinsic neurons to dopaminergic neurons as a promising candidate for experimental evaluation. It differentiates well between trained and novel stimuli, demonstrating robust performance across a range of model parameters. [ABSTRACT FROM AUTHOR]

A LIM homeodomain transcription factor Apterous (Ap) regulates embryonic and larval neurodevelopment in Drosophila. Although Ap is still expressed in the adult brain, it remains elusive whether Ap is involved in neurodevelopmental events in the adult brain because flies homozygous for ap mutations are usually lethal before they reach the adult stage. In this study, using adult escapers of ap knockout (KO) homozygotes, we examined whether the complete lack of ap expression affects the morphology of the mushroom body (MB) neurons and Pigment-dispersing factor (Pdf)-positive clock neurons in the adult brain. Although ap KO escapers showed severe structural defects of MB neurons, no clear morphological defects were found in Pdf-positive clock neurons. These results suggest that Ap in the adult brain is essential for the neurodevelopment of specific ap -positive neurons, but it is not necessarily involved in the development of all ap -positive neurons. • Drosophila apterous (ap) is essential for embryonic and larval neurodevelopment. • ap is expressed in the adult mushroom body (MB) and Pdf neurons. • ap knockout flies showed severe structural defects of MB neurons. • No morphological defects of Pdf neurons were detected in ap knockout flies. • ap does not necessarily regulate the development of all ap -positive neurons in adults. [ABSTRACT FROM AUTHOR]

Larvae of the fruit fly Drosophila melanogaster are a powerful study case for understanding the neural circuits underlying behavior. Indeed, the numerical simplicity of the larval brain has permitted the reconstruction of its synaptic connectome, and genetic tools for manipulating single, identified neurons allow neural circuit function to be investigated with relative ease and precision. We focus on one of the most complex neurons in the brain of the larva (of either sex), the GABAergic anterior paired lateral neuron (APL). Using behavioral and connectomic analyses, optogenetics, Ca2+ imaging, and pharmacology, we study how APL affects associative olfactory memory. We first provide a detailed account of the structure, regional polarity, connectivity, and metamorphic development of APL, and further confirm that optogenetic activation of APL has an inhibiting effect on its main targets, the mushroom body Kenyon cells. All these findings are consistent with the previously identified function of APL in the sparsening of sensory representations. To our surprise, however, we found that optogenetically activating APL can also have a strong rewarding effect. Specifically, APL activation together with odor presentation establishes an odor-specific, appetitive, associative short-term memory, whereas naive olfactory behavior remains unaffected. An acute, systemic inhibition of dopamine synthesis as well as an ablation of the dopaminergic pPAM neurons impair reward learning through APL activation. Our findings provide a study case of complex circuit function in a numerically simple brain, and suggest a previously unrecognized capacity of central-brain GABAergic neurons to engage in dopaminergic reinforcement. [ABSTRACT FROM AUTHOR]

Mature behaviors emerge from neural circuits sculpted by genetic programs and spontaneous and evoked neural activity. However, how neural activity is refined to drive maturation of learned behavior remains poorly understood. Here, we explore how transient hormonal signaling coordinates a neural activity state transition and maturation of associative learning. We identify spontaneous, asynchronous activity in a Drosophila learning and memory brain region, the mushroom body. This activity declines significantly over the first week of adulthood. Moreover, this activity is generated cell-autonomously via Cacophony voltage-gated calcium channels in a single cell type, α'/β' Kenyon cells. Juvenile hormone, a crucial developmental regulator, acts transiently in α'/β' Kenyon cells during a young adult sensitive period to downregulate spontaneous activity and enable subsequent enhanced learning. Hormone signaling in young animals therefore controls a neural activity state transition and is required for improved associative learning, providing insight into the maturation of circuits and behavior.

How memories of past events influence behavior is a key question in neuroscience. The major associative learning center in Drosophila, the mushroom body (MB), communicates to the rest of the brain through mushroom body output neurons (MBONs). While 21 MBON cell types have their dendrites confined to small compartments of the MB lobes, analysis of EM connectomes revealed the presence of an additional 14 MBON cell types that are atypical in having dendritic input both within the MB lobes and in adjacent brain regions. Genetic reagents for manipulating atypical MBONs and experimental data on their functions have been lacking. In this report we describe new cell-type-specific GAL4 drivers for many MBONs, including the majority of atypical MBONs that extend the collection of MBON driver lines we have previously generated (Aso et al., 2014a; Aso et al., 2016; Aso et al., 2019). Using these genetic reagents, we conducted optogenetic activation screening to examine their ability to drive behaviors and learning. These reagents provide important new tools for the study of complex behaviors in Drosophila.

In well-established first-order conditioning experiments, the concurrence of a sensory cue with reinforcement forms an association, allowing the cue to predict future reinforcement. In the insect mushroom body, a brain region central to learning and memory, such associations are encoded in the synapses between its intrinsic and output neurons. This process is mediated by the activity of dopaminergic neurons that encode reinforcement signals. In second-order conditioning, a new sensory cue is paired with an already established one that presumably activates dopaminergic neurons due to its predictive power of the reinforcement. We explored minimal circuit motifs in the mushroom body for their ability to support second-order conditioning using mechanistic models. We found that dopaminergic neurons can either be activated directly by the mushroom body’s intrinsic neurons or via feedback from the output neurons via several pathways. We demonstrated that the circuit motifs differ in their computational efficiency and robustness. Beyond previous research, we suggest an additional motif that relies on feedforward input of the mushroom body intrinsic neurons to dopaminergic neurons as a promising candidate for experimental evaluation. It differentiates well between trained and novel stimuli, demonstrating robust performance across a range of model parameters.

Memory formation and forgetting unnecessary memory must be balanced for adaptive animal behavior. While cyclic AMP (cAMP) signaling via dopamine neurons induces memory formation, here we report that cyclic guanine monophosphate (cGMP) signaling via dopamine neurons launches forgetting of unconsolidated memory in Drosophila. Genetic screening and proteomic analyses showed that neural activation induces the complex formation of a histone H3K9 demethylase, Kdm4B, and a GMP synthetase, Bur, which is necessary and sufficient for forgetting unconsolidated memory. Kdm4B/Bur is activated by phosphorylation through NO-dependent cGMP signaling via dopamine neurons, inducing gene expression, including kek2 encoding a presynaptic protein. Accordingly, Kdm4B/Bur activation induced presynaptic changes. Our data demonstrate a link between cGMP signaling and synapses via gene expression in forgetting, suggesting that the opposing functions of memory are orchestrated by distinct signaling via dopamine neurons, which affects synaptic integrity and thus balances animal behavior. [ABSTRACT FROM AUTHOR]

In the last decade, researchers using Drosophila melanogaster have made extraordinary progress in uncovering the mysteries underlying learning and memory. This progress has been propelled by the amazing toolkit available that affords combined behavioral, molecular, electrophysiological, and systems neuroscience approaches. The arduous reconstruction of electron microscopic images resulted in a first-generation connectome of the adult and larval brain, revealing complex structural interconnections between memory-related neurons. This serves as substrate for future investigations on these connections and for building complete circuits from sensory cue detection to changes in motor behavior. Mushroom body output neurons (MBOn) were discovered, which individually forward information from discrete and non-overlapping compartments of the axons of mushroom body neurons (MBn). These neurons mirror the previously discovered tiling of mushroom body axons by inputs from dopamine neurons and have led to a model that ascribes the valence of the learning event, either appetitive or aversive, to the activity of different populations of dopamine neurons and the balance of MBOn activity in promoting avoidance or approach behavior. Studies of the calyx, which houses the MBn dendrites, have revealed a beautiful microglomeruluar organization and structural changes of synapses that occur with long-term memory (LTM) formation. Larval learning has advanced, positioning it to possibly lead in producing new conceptual insights due to its markedly simpler structure over the adult brain. Advances were made in how cAMP response element-binding protein interacts with protein kinases and other transcription factors to promote the formation of LTM. New insights were made on Orb2, a prion-like protein that forms oligomers to enhance synaptic protein synthesis required for LTM formation. Finally, Drosophila research has pioneered our understanding of the mechanisms that mediate permanent and transient active forgetting, an important function of the brain along with acquisition, consolidation, and retrieval. This was catalyzed partly by the identification of memory suppressor genes-genes whose normal function is to limit memory formation. [ABSTRACT FROM AUTHOR]

The selective pressures leading to the elaboration of downstream, integrative processing centres, such as the mammalian neocortex or insect mushroom bodies, are often unclear. In Heliconius butterflies, the mushroom bodies are two to four times larger than those of their Heliconiini relatives, and the largest known in Lepidoptera. Heliconiini lay almost exclusively on Passiflora, which exhibit a remarkable diversity of leaf shape, and it has been suggested that the mushroom body expansion of Heliconius may have been driven by the cognitive demands of recognizing and learning leaf shapes of local host plants. We test this hypothesis using two complementary methods: (i) phylogenetic comparative analyses to test whether variation in mushroom body size is associated with the morphological diversity of host plants exploited across the Heliconiini; and (ii) shape-learning experiments using six Heliconiini species. We found that variation in the range of leaf morphologies used by Heliconiini was not associated with mushroom body volume. Similarly, we find interspecific differences in shape-learning ability, but Heliconius are not overall better shape learners than other Heliconiini. Together these results suggest that the visual recognition and learning of host plants was not a main factor driving the diversity of mushroom body size in this tribe. [ABSTRACT FROM AUTHOR]

The precise control of motor movements is of fundamental importance to all behaviors in the animal kingdom. Efficient motor behavior depends on dedicated neuronal circuits - such as those in the cerebellum - that are controlled by extensive genetic programs. Autosomal recessive cerebellar ataxias (ARCAs) provide a valuable entry point into how interactions between genetic programs maintain cerebellar motor circuits. We previously identified a striking enrichment of DNA repair genes in ARCAs. How dysfunction of ARCA-associated DNA repair genes leads to preferential cerebellar dysfunction and impaired motor function is however unknown. The expression of ARCA DNA repair genes is not specific to the cerebellum. Only a limited number of animal models for DNA repair ARCAs exist, and, even for these, the interconnection between DNA repair defects, cerebellar circuit dysfunction, and motor behavior is barely established. We used Drosophila melanogaster to characterize the function of ARCA-associated DNA repair genes in the mushroom body (MB), a structure in the Drosophila central brain that shares structural features with the cerebellum. Here, we demonstrate that the MB is required for efficient startle-induced and spontaneous motor behaviors. Inhibition of synaptic transmission and loss-of-function of ARCA-associated DNA repair genes in the MB affected motor behavior in several assays. These motor deficits correlated with increased levels of MB DNA damage, MB Kenyon cell apoptosis and/or alterations in MB morphology. We further show that expression of genes involved in glutamate signaling pathways are highly, specifically, and persistently elevated in the postnatal human cerebellum. Manipulation of glutamate signaling in the MB induced motor defects, Kenyon cell DNA damage and apoptosis. Importantly, pharmacological reduction of glutamate signaling in the ARCA DNA repair models rescued the identified motor deficits, suggesting a role for aberrant glutamate signaling in ARCA-DNA repair disorders. In conclusion, our data highlight the importance of ARCA-associated DNA repair genes and glutamate signaling pathways to the cerebellum, the Drosophila MB and motor behavior. We propose that glutamate signaling may confer preferential cerebellar vulnerability in ARCA-associated DNA repair disorders. Targeting glutamate signaling could provide an exciting therapeutic entry point in this large group of so far untreatable disorders. [ABSTRACT FROM AUTHOR]

Efficient spatial orientation in the natural environment is crucial for the survival of most animal species. Cataglyphis desert ants possess excellent navigational skills. After far-ranging foraging excursions, the ants return to their inconspicuous nest entrance using celestial and panoramic cues. This review focuses on the question about how naïve ants acquire the necessary spatial information and adjust their visual compass systems. Naïve ants perform structured learning walks during their transition from the dark nest interior to foraging under bright sunlight. During initial learning walks, the ants perform rotational movements with nest-directed views using the earth's magnetic field as an earthbound compass reference. Experimental manipulations demonstrate that specific sky compass cues trigger structural neuronal plasticity in visual circuits to integration centers in the central complex and mushroom bodies. During learning walks, rotation of the sky-polarization pattern is required for an increase in volume and synaptic complexes in both integration centers. In contrast, passive light exposure triggers light-spectrum (especially UV light) dependent changes in synaptic complexes upstream of the central complex. We discuss a multisensory circuit model in the ant brain for pathways mediating structural neuroplasticity at different levels following passive light exposure and multisensory experience during the performance of learning walks. [ABSTRACT FROM AUTHOR]

Novel genes have the potential to drive the evolution of new biological mechanisms, or to integrate into preexisting regulatory circuits and contribute to the regulation of older, conserved biological functions. One such gene, the novel insect-specific gene oskar, was first identified based on its role in establishing the Drosophila melanogaster germ line. We previously showed that this gene likely arose through an unusual domain transfer event involving bacterial endosymbionts and played a somatic role before evolving its well-known germ line function. Here, we provide empirical support for this hypothesis in the form of evidence for a neural role for oskar. We show that oskar is expressed in the adult neural stem cells of a hemimetabolous insect, the cricket Gryllus bimaculatus. In these stem cells, called neuroblasts, oskar is required together with the ancient animal transcription factor Creb to regulate long-term (but not short-term) olfactory memory. We provide evidence that oskar positively regulates Creb, which plays a conserved role in long-term memory across animals, and that oskar in turn may be a direct target of Creb. Together with previous reports of a role for oskar in nervous system development and function in crickets and flies, our results are consistent with the hypothesis that oskar's original somatic role may have been in the insect nervous system. Moreover, its colocalization and functional cooperation with the conserved pluripotency gene piwi in the nervous system may have facilitated oskar's later co-option to the germ line in holometabolous insects. [ABSTRACT FROM AUTHOR]

Dysregulation of HDAC4 expression and/or nucleocytoplasmic shuttling results in impaired neuronal morphogenesis and long-term memory in Drosophila melanogaster. A recent genetic screen for genes that interact in the same molecular pathway as HDAC4 identified the cytoskeletal adapter Ankyrin2 (Ank2). Here we sought to investigate the role of Ank2 in neuronal morphogenesis, learning and memory. We found that Ank2 is expressed widely throughout the Drosophila brain where it localizes predominantly to axon tracts. Pan-neuronal knockdown of Ank2 in the mushroom body, a region critical for memory formation, resulted in defects in axon morphogenesis. Similarly, reduction of Ank2 in lobular plate tangential neurons of the optic lobe disrupted dendritic branching and arborization. Conditional knockdown of Ank2 in the mushroom body of adult Drosophila significantly impaired long-term memory (LTM) of courtship suppression, and its expression was essential in the γ neurons of the mushroom body for normal LTM. In summary, we provide the first characterization of the expression pattern of Ank2 in the adult Drosophila brain and demonstrate that Ank2 is critical for morphogenesis of the mushroom body and for the molecular processes required in the adult brain for the formation of long-term memories. [ABSTRACT FROM AUTHOR]

How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in Drosophila, multiple compartments of the mushroom body act in parallel to assign a valence to a stimulus. Here, we show that appetitive memories stored in different compartments induce different levels of upwind locomotion. Using a photoactivation screen of a new collection of split-GAL4 drivers and EM connectomics, we identified a cluster of neurons postsynaptic to the mushroom body output neurons (MBONs) that can trigger robust upwind steering. These UpWind Neurons (UpWiNs) integrate inhibitory and excitatory synaptic inputs from MBONs of appetitive and aversive memory compartments, respectively. After formation of appetitive memory, UpWiNs acquire enhanced response to reward-predicting odors as the response of the inhibitory presynaptic MBON undergoes depression. Blocking UpWiNs impaired appetitive memory and reduced upwind locomotion during retrieval. Photoactivation of UpWiNs also increased the chance of returning to a location where activation was terminated, suggesting an additional role in olfactory navigation. Thus, our results provide insight into how learned abstract valences are gradually transformed into concrete memory-driven actions through divergent and convergent networks, a neuronal architecture that is commonly found in the vertebrate and invertebrate brains.

The precise control of motor movements is of fundamental importance to all behaviors in the animal kingdom. Efficient motor behavior depends on dedicated neuronal circuits – such as those in the cerebellum – that are controlled by extensive genetic programs. Autosomal recessive cerebellar ataxias (ARCAs) provide a valuable entry point into how interactions between genetic programs maintain cerebellar motor circuits. We previously identified a striking enrichment of DNA repair genes in ARCAs. How dysfunction of ARCA-associated DNA repair genes leads to preferential cerebellar dysfunction and impaired motor function is however unknown. The expression of ARCA DNA repair genes is not specific to the cerebellum. Only a limited number of animal models for DNA repair ARCAs exist, and, even for these, the interconnection between DNA repair defects, cerebellar circuit dysfunction, and motor behavior is barely established. We used Drosophila melanogaster to characterize the function of ARCA-associated DNA repair genes in the mushroom body (MB), a structure in the Drosophila central brain that shares structural features with the cerebellum. Here, we demonstrate that the MB is required for efficient startle-induced and spontaneous motor behaviors. Inhibition of synaptic transmission and loss-of-function of ARCA-associated DNA repair genes in the MB affected motor behavior in several assays. These motor deficits correlated with increased levels of MB DNA damage, MB Kenyon cell apoptosis and/or alterations in MB morphology. We further show that expression of genes involved in glutamate signaling pathways are highly, specifically, and persistently elevated in the postnatal human cerebellum. Manipulation of glutamate signaling in the MB induced motor defects, Kenyon cell DNA damage and apoptosis. Importantly, pharmacological reduction of glutamate signaling in the ARCA DNA repair models rescued the identified motor deficits, suggesting a role for aberrant glutamate signaling in ARCA-DNA repair disorders. In conclusion, our data highlight the importance of ARCA-associated DNA repair genes and glutamate signaling pathways to the cerebellum, the Drosophila MB and motor behavior. We propose that glutamate signaling may confer preferential cerebellar vulnerability in ARCA-associated DNA repair disorders. Targeting glutamate signaling could provide an exciting therapeutic entry point in this large group of so far untreatable disorders.

Memory guides behavior across widely varying environments and must therefore be both sufficiently specific and general. A memory too specific will be useless in even a slightly different environment, while an overly general memory may lead to suboptimal choices. Animals successfully learn to both distinguish between very similar stimuli and generalize across cues. Rather than forming memories that strike a balance between specificity and generality, Drosophila can flexibly categorize a given stimulus into different groups depending on the options available. We asked how this flexibility manifests itself in the well-characterized learning and memory pathways of the fruit fly. We show that flexible categorization in neuronal activity as well as behavior depends on the order and identity of the perceived stimuli. Our results identify the neural correlates of flexible stimulus-categorization in the fruit fly.

Hunger is a motivational drive that promotes feeding, and it can be generated by the physiological need to consume nutrients as well as the hedonic properties of food. Brain circuits and mechanisms that regulate feeding have been described, but which of these contribute to the generation of motive forces that drive feeding is unclear. Here, we describe our first efforts at behaviorally and neuronally distinguishing hedonic from homeostatic hunger states in Drosophila melanogaster and propose that this system can be used as a model to dissect the molecular mechanisms that underlie feeding motivation. We visually identify and quantify behaviors exhibited by hungry flies and find that increased feeding duration is a behavioral signature of hedonic feeding motivation. Using a genetically encoded marker of neuronal activity, we find that the mushroom body (MB) lobes are activated by hedonic food environments, and we use optogenetic inhibition to implicate a dopaminergic neuron cluster (protocerebral anterior medial [PAM]) to α’/β’ MB circuit in hedonic feeding motivation. The identification of discrete hunger states in flies and the development of behavioral assays to measure them offers a framework to begin dissecting the molecular and circuit mechanisms that generate motivational states in the brain.

Recent studies revealed behaviorally defined sleep is conserved across broad species from insect to human. For evolutional analysis, it is critical to determine how homologous genes regulate the homologous function among species. Drosophila melanogaster shares numerous sleep related genes with mammals including Sik3 , salt-inducible kinase 3, whose mutation caused long sleep both in mouse and fruit fly. The Drosophila rdgB (retinal degeneration B) encodes a membrane-associated phosphatidylinositol transfer protein and its mutation caused light-induced degeneration of photoreceptor cells. rdgB mutation also impaired phototransduction and olfactory behavior, indicating rdgB is involved in the normal neural transmission. Mammalian rdgB homologue, Pitpnm2 (phosphatidylinositol transfer protein membrane-associated 2) was discovered as one of SNIPPs (sleep-need index phosphoproteins), suggesting its role in sleep. Here, we show that rdgB is involved in sleep regulation in Drosophila. Pan-neuronal and mushroom body (MB) specific rdgB knockdown decreased nocturnal sleep. MB neurons play a dominant role, since the rescue of rdgB expression only in MB neurons in pan-neuronal knockdown reversed the sleep reducing effect of rdgB knockdown. These results revealed the sleep-related function of rdgB in Drosophila which may be conserved across species. • rdgB RNAi in all neurons decreased sleep in Drosophila melanogaster. • Exclusion of mushroom body rescued sleep decrease by pan-neuronal rgdB RNAi. • rdgB RNAi specifically in mushroom body neurons decreased sleep during night. [ABSTRACT FROM AUTHOR]

Bisphenol AP (BPAP), an environmental endocrine disruptor, may cause neurodevelopmental disorders affecting human health. Studies have shown that BPAP impacts hormone synthesis and metabolism, causes social behavior abnormalities, and induces anxiety-like behavioral impairments in mice. However, evidence for the neurobehavioral effects of BPAP is still lacking. Here, we examined the toxic effects of BPAP on neurodevelopment using a Drosophila model. We assessed the role of BPAP exposure in autism-like behavior and explored the underlying mechanisms. Our findings indicated that BPAP exposure reduced pupation and eclosion rates and delayed growth in Drosophila. Furthermore, BPAP exposure caused autism-like behaviors, characterized by increased grooming times and aberrant social interactions, along with abnormalities in locomotor activity, as well as learning and memory ability. Mechanistically, we found that BPAP decreases the number of neuroblasts (NBs) and mature intermediate neural progenitors (INPs) in the 3rd larval brain, impairing axon guidance in the mushroom body of the adult Drosophila brain. Additionally, our transcriptome analysis revealed that BPAP exposure alters the expression of neurodevelopment-related genes (Nplp3 , sand , lush , and orco) and affects the estrogen signaling pathway (Hsp70Ab , Hsp70Bc , Hsp70Ba , and Hsp70Bb). These changes potentially explain the BPAP-induced autism-like behavior in Drosophila. [Display omitted] • BPAP exposure reduced pupation and eclosion rate and delayed growth in Drosophila. • BPAP exposure induced a variety of neurobehavioural deficits in Drosophila. • BPAP exposure reduced the number of neuroblasts in the larval brain. • BPAP exposure impaired axon guidance in the adult Drosophila brain. • BPAP exposure altered neurodevelopmental genes expression in the adult brain. [ABSTRACT FROM AUTHOR]

The way neurons in the brain rewire in larvae as they turn to adult fruit flies sheds light on how complete metamorphosis was ‘invented’ over the course of evolution.

Understanding the physiological mechanisms that modulate memory acquisition and consolidation remains among the most ambitious questions in neuroscience. Massive efforts have been dedicated to deciphering how experience affects behavior, and how different physiological and sensory phenomena modulate memory. Our ability to encode, consolidate and retrieve memories depends on internal drives, and sleep stands out among the physiological processes that affect memory: one of the most relatable benefits of sleep is the aiding of memory that occurs in order to both prepare the brain to learn new information, and after a learning task, to consolidate those new memories. Drosophila lends itself to the study of the interactions between memory and sleep. The fruit fly provides incomparable genetic resources, a mapped connectome, and an existing framework of knowledge on the molecular, cellular, and circuit mechanisms of memory and sleep, making the fruit fly a remarkable model to decipher the sophisticated regulation of learning and memory by the quantity and quality of sleep. Research in Drosophila has stablished not only that sleep facilitates learning in wild-type and memory-impaired animals, but that sleep deprivation interferes with the acquisition of new memories. In addition, it is well-accepted that sleep is paramount in memory consolidation processes. Finally, studies in Drosophila have shown that that learning itself can promote sleep drive. Nevertheless, the molecular and network mechanisms underlying this intertwined relationship are still evasive. Recent remarkable work has shed light on the neural substrates that mediate sleep-dependent memory consolidation. In a similar way, the mechanistic insights of the neural switch control between sleep-dependent and sleep-independent consolidation strategies were recently described. This review will discuss the regulation of memory by sleep in Drosophila, focusing on the most recent advances in the field and pointing out questions awaiting to be investigated. [ABSTRACT FROM AUTHOR]

Abstract Background The evolution of the brain and its major neuropils in Panarthropoda (comprising Arthropoda, Tardigrada and Onychophora) remains enigmatic. As one of the closest relatives of arthropods, onychophorans are regarded as indispensable for a broad understanding of the evolution of panarthropod organ systems, including the brain, whose anatomical and functional organisation is often used to gain insights into evolutionary relations. However, while numerous recent studies have clarified the organisation of many arthropod nervous systems, a detailed investigation of the onychophoran brain with current state-of-the-art approaches is lacking, and further inconsistencies in nomenclature and interpretation hamper its understanding. To clarify the origins and homology of cerebral structures across panarthropods, we analysed the brain architecture in the onychophoran Euperipatoides rowelli by combining X-ray micro-computed tomography, histology, immunohistochemistry, confocal microscopy, and three-dimensional reconstruction. Results Here, we use this detailed information to generate a consistent glossary for neuroanatomical studies of Onychophora. In addition, we report novel cerebral structures, provide novel details on previously known brain areas, and characterise further structures and neuropils in order to improve the reproducibility of neuroanatomical observations. Our findings support homology of mushroom bodies and central bodies in onychophorans and arthropods. Their antennal nerve cords and olfactory lobes most likely evolved independently. In contrast to previous reports, we found no evidence for second-order visual neuropils, or a frontal ganglion in the velvet worm brain. Conclusion We imaged the velvet worm nervous system at an unprecedented level of detail and compiled a comprehensive glossary of known and previously uncharacterised neuroanatomical structures to provide an in-depth characterisation of the onychophoran brain architecture. We expect that our data will improve the reproducibility and comparability of future neuroanatomical studies.

Mushroom bodies (MB) of adult Drosophila have a core of thousands of Kenyon neurons; axons of the early-born g class form a medial lobe and those from later-born α'β' and αβ classes form both medial and vertical lobes. The larva, however, hatches with only γ neurons and forms a vertical lobe 'facsimile' using larval-specific axon branches from its γ neurons. MB input (MBINs) and output (MBONs) neurons divide the Kenyon neuron lobes into discrete computational compartments. The larva has 10 such compartments while the adult has 16. We determined the fates of 28 of the 32 MBONs and MBINs that define the 10 larval compartments. Seven compartments are subsequently incorporated into the adult MB; four of their MBINs die, while 12 MBINs/MBONs remodel to function in adult compartments. The remaining three compartments are larval specific. At metamorphosis their MBIN/MBONs trans-differentiate, leaving the MB for other adult brain circuits. The adult vertical lobes are made de novo using MBONs/MBINs recruited from pools of adult-specific neurons. The combination of cell death, compartment shifting, trans-differentiation, and recruitment of new neurons result in no larval MBIN-MBON connections being maintained through metamorphosis. At this simple level, then, we find no anatomical substrate for a memory trace persisting from larva to adult. The adult phenotype of the trans-differentiating neurons represents their evolutionarily ancestral phenotype while their larval phenotype is a derived adaptation for the larval stage. These cells arise primarily within lineages that also produce permanent MBINs and MBONs, suggesting that larval specifying factors may allow information related to birth-order or sibling identity to be interpreted in a modified manner in the larva to allow these neurons to acquire larval phenotypic modifications. The loss of such factors at metamorphosis then allows these neurons to revert to their ancestral functions in the adult.

Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective ‘teacher’ by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the ‘student’ compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.

Understanding the physiological mechanisms that modulate memory acquisition and consolidation remains among the most ambitious questions in neuroscience. Massive efforts have been dedicated to deciphering how experience affects behavior, and how different physiological and sensory phenomena modulate memory. Our ability to encode, consolidate and retrieve memories depends on internal drives, and sleep stands out among the physiological processes that affect memory: one of the most relatable benefits of sleep is the aiding of memory that occurs in order to both prepare the brain to learn new information, and after a learning task, to consolidate those new memories. Drosophila lends itself to the study of the interactions between memory and sleep. The fruit fly provides incomparable genetic resources, a mapped connectome, and an existing framework of knowledge on the molecular, cellular, and circuit mechanisms of memory and sleep, making the fruit fly a remarkable model to decipher the sophisticated regulation of learning and memory by the quantity and quality of sleep. Research in Drosophila has stablished not only that sleep facilitates learning in wild-type and memory-impaired animals, but that sleep deprivation interferes with the acquisition of new memories. In addition, it is well-accepted that sleep is paramount in memory consolidation processes. Finally, studies in Drosophila have shown that that learning itself can promote sleep drive. Nevertheless, the molecular and network mechanisms underlying this intertwined relationship are still evasive. Recent remarkable work has shed light on the neural substrates that mediate sleep-dependent memory consolidation. In a similar way, the mechanistic insights of the neural switch control between sleep-dependent and sleep-independent consolidation strategies were recently described. This review will discuss the regulation of memory by sleep in Drosophila, focusing on the most recent advances in the field and pointing out questions awaiting to be investigated.

The mushroom body (MB) is a computational center in the Drosophila brain. The intricate neural circuits of the mushroom body enable it to store associative memories and process sensory and internal state information. The mushroom body is composed of diverse types of neurons that are precisely assembled during development. Tremendous efforts have been made to unravel the molecular and cellular mechanisms that build the mushroom body. However, we are still at the beginning of this challenging quest, with many key aspects of mushroom body assembly remaining unexplored. In this review, I provide an in-depth overview of our current understanding of mushroom body development and pertinent knowledge gaps.

The larval development of the endangered freshwater mussel Margaritifera margaritifera (L.) represents one of the most unique parasitism among naiads, in which larva parasite the fish gills for several months. Despite the importance of this parasitic phase to successfully culture the freshwater mussel, the larval morphogenesis remains understudied. To describe the parasitic larval development and metamorphosis, Atlantic salmon (Salmo salar L.) were exposed to glochidia, sampled periodically to visualize the gills by stereomicroscopy and light microscopy and results were summarized throughout three developmental stages. Once attached to the fish gills, glochidia changed their morphology within the first days and acquired an intermediate stage termed mushroom larva due to the presence of the mushroom body and the zip membrane, both structures are transitory and distinctive of this long-lasting parasitism. The zip membrane, located at the valve cleft, may play a unique role in the isolation and acquisition of non-particulate nutrients from the fish, while the mushroom body of the mantle accumulates abundant intracytoplasmic lipid droplets. After 200 days, a successful metamorphosis was evidenced by the formation of a complete set of post-larval organs, pointing to the acquisition of different functionality, which will be essential for the settlement and deposit-feeding into the riverbed. Among the post-larval organs, the byssal complex of the post-larval foot was described for the first time at the end of the parasitic stage of naiads. In conclusion, this study provides an overview of the larval morphogenesis of M. margaritifera, from glochidium to post-larva, essential for understanding the parasitic interaction between the freshwater mussel larva and the fish host. Moreover, the morphological techniques and the hallmarks described might be applicable to optimize and monitor the larval developmental status during one of the most critical stages of the captive breeding programmes of endangered freshwater mussels.

Abstract Background The brain anatomy in the clade Spiralia can vary from simple, commissural brains (e.g., gastrotrichs, rotifers) to rather complex, partitioned structures (e.g., in cephalopods and annelids). How often and in which lineages complex brains evolved still remains unclear. Nemerteans are a clade of worm-like spiralians, which possess a complex central nervous system (CNS) with a prominent brain, and elaborated chemosensory and neuroglandular cerebral organs, which have been previously suggested as homologs to the annelid mushroom bodies. To understand the developmental and evolutionary origins of the complex brain in nemerteans and spiralians in general, we investigated details of the neuroanatomy and gene expression in the brain and cerebral organs of the juveniles of nemertean Lineus ruber. Results In the juveniles, the CNS is already composed of all major elements present in the adults, including the brain, paired longitudinal lateral nerve cords, and an unpaired dorsal nerve cord, which suggests that further neural development is mostly related with increase in the size but not in complexity. The ultrastructure of the juvenile cerebral organ revealed that it is composed of several distinct cell types present also in the adults. The 12 transcription factors commonly used as brain cell type markers in bilaterians show region-specific expression in the nemertean brain and divide the entire organ into several molecularly distinct areas, partially overlapping with the morphological compartments. Additionally, several of the mushroom body-specific genes are expressed in the developing cerebral organs. Conclusions The dissimilar expression of molecular brain markers between L. ruber and the annelid Platynereis dumerilii indicates that the complex brains present in those two species evolved convergently by independent expansions of non-homologous regions of a simpler brain present in their last common ancestor. Although the same genes are expressed in mushroom bodies and cerebral organs, their spatial expression within organs shows apparent differences between annelids and nemerteans, indicating convergent recruitment of the same genes into patterning of non-homologous organs or hint toward a more complicated evolutionary process, in which conserved and novel cell types contribute to the non-homologous structures.

Cataglyphis desert ants are skilled visual navigators. Here, I present a brief overview of multisensory learning and neuronal plasticity in ants, with a particular focus on the transition from the dark nest interior to performing first foraging trips. This highlights desert ants as experimental models for studying neuronal mechanisms underlying behavioral development into successful navigators. [ABSTRACT FROM AUTHOR]

The swallowtail butterfly, Papilio xuthus , has excellent color discrimination abilities, and its visible light spectrum is notably wide. We discuss the neural basis of color vision in P. xuthus , highlighting some of the evolutionary adaptations in this species in relation to other insects. These adaptations include inter-photoreceptor (PR) interactions that produce spectral-opponent PRs, and complex higher order color-coding neurons. [ABSTRACT FROM AUTHOR]

The principles of how brain circuits establish themselves during development are largely conserved across animal species. Connections made during embryonic development that are appropriate for an early life stage are frequently remodelled later in ontogeny via pruning and subsequent regrowth to generate adult-specific connectivity. The mushroom body of the fruit fly Drosophila melanogaster is a well-established model circuit for examining the cellular mechanisms underlying neurite remodelling. This central brain circuit integrates sensory information with learned and innate valences to adaptively instruct behavioural decisions. Thereby, the mushroom body organizes adaptive behaviour, such as associative learning. However, little is known about the specific aspects of behaviour that require mushroom body remodelling. Here, we used genetic interventions to prevent the intrinsic neurons of the larval mushroom body (γ-type Kenyon cells) from remodelling. We asked to what degree remodelling deficits resulted in impaired behaviour. We found that deficits caused hyperactivity and mild impairment in differential aversive olfactory learning, but not appetitive learning. Maintenance of circadian rhythm and sleep were not affected. We conclude that neurite pruning and regrowth of γ-type Kenyon cells is not required for the establishment of circuits that mediate associative odour learning per se, but it does improve distinct learning tasks.