Presynaptic contact and activity opposingly regulate postsynaptic dendrite outgrowth

Abstract

The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.

Drosophilamales require the longitudinal stretch receptors to tremulate their abdomen and produce substrate-borne signals during courtship

“…However, using 7-33-Gal4 11 to drive expression of UAS-shi ts in nociceptive sensory ddaC body wall neurons, which localise near the dbd neurons but are not associated with abdominal muscles 18 (Supplementary Figure S2B), did not lead to an increased occurrence of bobbing (Supplementary Figure S2C). As with larval dbd neurons, we found that the acetylcholine marker ( Cha -Gal4) drove expression in adult dbd neurons, indicating that dbd neurons express choline acetyltransferase (ChaT) and are cholinergic 33,34 (Supplementary Figure S3A). Consistent with this, using a promoter to express the Gal4 inhibitor Gal80 specifically in cholinergic neurons ( ChaT-Gal80 ) 25 reduced bobbing in Clh8-Gal4>UAS-shi ts males, while expressing Gal80 specifically in glutamatergic neurons ( VGlut-Gal80 ) 35 had no effect (Supplementary Figure S2B).…”

“…However, using 7-33-Gal4 11 to drive expression of UAS-shi ts in nociceptive sensory ddaC body wall neurons, which localise near the dbd neurons but are not associated with abdominal muscles 18 (Supplementary Figure S2B), did not lead to an increased occurrence of bobbing (Supplementary Figure S2C). As with larval dbd neurons, we found that the acetylcholine marker (Cha-Gal4) drove expression in adult dbd neurons, indicating that dbd neurons express choline acetyltransferase (ChaT) and are cholinergic 33,34 (Supplementary Figure S3A).…”

“…This serves as a striking example of developmental neuronal plasticity. Further findings and the comparison with data on larval dbd will help determine the specific mechanisms of stretch-sensing required for tremulations 11,22,34,39,49 .…”

Invariant synaptic density across species

“…Despite large and significant differences in synaptic density, mutant dendritic morphologies were not significantly different from wild-type ones, indicating that the effect is independent of overall arbour morphology (Figure S2B-E). These findings underscore the need for precise spatial positioning and neuronal activity during development to establish appropriate synaptic connectivity and density (40,41).…”

Hacking brain development to test models of sensory coding

“…Using chemical and genetic approaches, we increase and decrease Kenyon cell number and Kenyon cell input number. This approach adds to a growing body of literature in which researchers engineer cell biological changes to neurons in order to probe developmental algorithms or change circuit function (Dzirasa et al, 2022;Hawk et al, 2021;Heckman and Doe, 2022;Linneweber et al, 2020;Meng et al, 2019;Pechuk et al, 2022;Pop et al, 2020;Prieto-Godino et al, 2020). Both the developmental and functional results force us to rethink assumptions and predictions about how the structure of connectivity influences odor representations and learned associations.…”