Biology subjects

Caron, S. J. C.

Publications and source records attributed to Caron, S. J. C..

7 recordsLinked to original sources

bioRxiv2026

Arc capsid signaling between serotonergic and dopaminergic neurons sets sleep depth in Drosophila

Arc genes evolved from Ty3 retrotransposons and encode proteins that self-assemble into virus-like capsids that package and transfer RNA between cells. This capsid-forming property may mediate a form of intercellular signaling distinct from classical synaptic transmission, but whether it operates within a defined neuronal system to control an ongoing behavior remains unclear. Here we show that Arc-dependent capsid signaling links serotonergic and PAM neurons to set sleep depth in Drosophila melanogaster. Loss of dArc genes deepened and consolidated sleep, increasing both sleep depth and the arousal threshold to mechanical stimulation, while leaving the diurnal sleep pattern intact. dArc1 was required in serotonergic neurons and, to a lesser extent, in PAM neurons, and both the loss-of-function phenotype and its rescue depended on capsid formation. Knocking down dArc1 in Sas-expressing cells, or Ptp10D in PAM neurons, reproduced the deeper, more consolidated sleep of dArc-/-flies, implicating the Sas-Ptp10D machinery in this signaling. These results identify Arc-dependent capsid signaling as a mechanism that links two modulatory neuronal populations to regulate an ongoing homeostatic behavior.

neuroscience↗

bioRxiv2025

Connectivity biases generate a learning hierarchy in the Drosophila mushroom body

Learning and memory centers must balance maximizing coding capacity with prioritizing biologically relevant information. Expansion layers, a circuit motif common to many learning and memory centers, including the insect mushroom body, transform dense sensory representations into sparse, distributed ones, and theoretical models propose that random connectivity within these layers maximizes coding capacity by generating highly discriminable responses. Yet this solution creates a fundamental problem: purely random connectivity treats all stimuli equally, without prioritizing survival-relevant cues over neutral ones. Here, we show that the Drosophila melanogaster mushroom body resolves this capacity-selectivity trade-off through systematic biases in projection neuron-Kenyon cell connectivity. Although connectivity is random at the single-cell level, some projection neuron types connect up to 15-fold more frequently than others. These biases translate directly into function: Kenyon cell responses scales with projection neuron connectivity, and the breadth of odor-evoked responses predicts learning performance. Odors activating more than 20% of Kenyon cells drive robust associative memories, whereas those activating fewer than 10% are poorly learned. VL1 projection neurons are a notable exception: despite their weak connectivity, they elicit broad Kenyon cell activity but fail to support learning, revealing a circuit-level gate on learning. These results show that the mushroom body embeds a learning hierarchy in its connectivity architecture, prioritizing ethologically relevant odors while preserving coding capacity for diverse associations.

neuroscience↗

bioRxiv2024

dArc1 controls sugar reward valuation in Drosophila melanogaster

The Arc genes -- which include Drosophila Arc1 and Arc2 (dArc) -- evolved from Ty3 retrotransposons and encode proteins that form virus-like capsids. These capsids enable a novel form of intercellular communication by transferring RNAs between cells. However, the specific neuronal circuits and brain processes Arc intercellular signaling regulates remain unknown. Here, we show that loss of both dArc genes in Drosophila melanogaster enhances associative learning in an appetitive conditioning paradigm, where flies associate an odor with sugar rewards. This increased learning performance arises from an increased valuation of sugar rewards: unlike wild-type flies, dArc-/- flies form abnormally strong associations even when the sugar reward is small or has no caloric value. We found that the {gamma}5-dopaminergic neurons of the protocerebral anterior medial (PAM) cluster, which encode the positive valence of sugar rewards, show heightened activity in response to sucrose in dArc-/- flies. We further show that the learning phenotype of dArc-/- flies depends on the formation of capsids, underscoring a direct role for capsid-mediated Arc signaling in sugar valuation. Our findings establish dArc genes as critical regulators of reward valuation in D. melanogaster, acting through a non-cell autonomous mechanism that relies on capsid-mediated communication between cells.

neuroscience↗

bioRxiv2023

Evolution of connectivity architecture in the Drosophila mushroom body

Brain evolution has primarily been studied at the macroscopic level by comparing the relative size of homologous brain centers between species. How neuronal circuits change at the cellular level over evolutionary time remains largely unanswered. Here, using a phylogenetically informed framework, we compare the olfactory circuits of three closely related Drosophila species that differ radically in their chemical ecology: the generalists Drosophila melanogaster and Drosophila simulans that feed on fermenting fruit, and Drosophila sechellia that specializes on ripe noni fruit. We examine a central part of the olfactory circuit that has not yet been investigated in these species -- the connections between the projection neurons of the antennal lobe and the Kenyon cells of the mushroom body, an associative brain center -- to identify species-specific connectivity patterns. We found that neurons encoding food odors -- the DC3 neurons in D. melanogaster and D. simulans and the DL2d neurons in D. sechellia -- connect more frequently with Kenyon cells, giving rise to species-specific biases in connectivity. These species-specific differences in connectivity reflect two distinct neuronal phenotypes: in the number of projection neurons or in the number of presynaptic boutons formed by individual projection neurons. Finally, behavioral analyses suggest that such increased connectivity enhances learning performance in an associative task. Our study shows how fine-grained aspects of connectivity architecture in an associative brain center can change during evolution to reflect the chemical ecology of a species.

neuroscience↗

bioRxiv2021

Mushroom body input connections form independently of sensory activity in Drosophila melanogaster

Associative brain centers, such as the insect mushroom body, need to represent sensory information in an efficient manner. In Drosophila melanogaster, the Kenyon cells of the mushroom body integrate inputs from a random set of olfactory projection neurons, but some projection neurons -- namely those activated by a few ethologically meaningful odors -- connect to Kenyon cells more frequently than others. This biased and random connectivity pattern is conceivably advantageous, as it enables the mushroom body to represent a large number of odors as unique activity patterns while prioritizing the representation of a few specific odors. How this connectivity pattern is established remains largely unknown. Here, we test whether the mechanisms patterning the connections between Kenyon cells and projection neurons depend on sensory activity or whether they are hardwired. We mapped a large number of mushroom body input connections in anosmic flies -- flies lacking the obligate odorant co-receptor Orco -- and in wildtype flies. Statistical analyses of these datasets reveal that the random and biased connectivity pattern observed between Kenyon cells and projection neurons forms normally in the absence of most olfactory sensory activity. This finding supports the idea that even comparatively subtle, population-level patterns of neuronal connectivity can be encoded by fixed genetic programs and are likely to be the result of evolved prioritization of ecologically and ethologically salient stimuli.

neuroscience↗

bioRxiv2021

Connectivity patterns shape sensory representation in a cerebellum-like network

Cerebellum-like structures -- such as the insect mushroom body -- are found in many brains and share a basic fan-out-fan-in network architecture. How the specific structural features of these networks give rise to their learning function remains largely unknown. To investigate this structure-function relationship, we developed a minimal computational model of the extensively studied Drosophila melanogaster mushroom body. We show how well-defined connectivity patterns between the Kenyon cells -- the constituent neurons of the mushroom body -- and their input projection neurons endow different functions, enabling the mushroom body to process olfactory information more efficiently. First, biases in the likelihoods at which individual projection neurons connect to Kenyon cells allow the mushroom body to prioritize the learning of particular, ethologically meaningful odors. Second, groups of projection neurons connecting preferentially to the same Kenyon cells facilitate the mushroom body to generalize across similar odors. Altogether, our results demonstrate how different connectivity patterns shape the representation space of a well-studied cerebellum-like network and impact its learning outcomes.

neuroscience↗

bioRxiv2020

Two parallel pathways convey distinct visual information to the Drosophila mushroom body

The ability to integrate input from different sensory systems is a fundamental property of many brains. Yet, the patterns of neuronal connectivity that underlie such multisensory integration remain poorly characterized. The Drosophila melanogaster mushroom body -- an associative center required for the formation of olfactory and visual memories -- is an ideal system to investigate how different sensory channels converge in higher-order brain centers. The neurons connecting the mushroom body to the olfactory system have been described in great detail, but input from other sensory systems remains poorly defined. Here, we use a range of anatomical and genetic techniques to identify two novel types of mushroom body input neuron that connect visual processing centers -- namely the lobula and the posterior lateral protocerebrum -- to the dorsal accessory calyx of the mushroom body. Together with previous work that described a pathway conveying visual information from the medulla to the ventral accessory calyx of the mushroom body (Vogt et al., 2016), our study defines a second, parallel pathway that is anatomically poised to convey information from the visual system to the dorsal accessory calyx. This connectivity pattern -- the segregation of the visual information into two separate pathways -- could be a fundamental feature of the neuronal architecture underlying multisensory integration in associative brain centers.

neuroscience↗