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Jacob, M. S.

Publications and source records attributed to Jacob, M. S..

3 recordsLinked to original sources

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↗

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↗

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↗