@article {67262, title = {A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS.}, journal = {eLife}, volume = {10}, year = {2021}, month = {2021 May 11}, abstract = {

The mechanisms specifying neuronal diversity are well-characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts), and identify them in a synapse-scale TEM reconstruction of the larval CNS. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.

}, issn = {2050-084X}, doi = {10.7554/eLife.67510}, author = {Mark, Brandon and Lai, Sen-Lin and Zarin, Aref Arzan and Manning, Laurina and Pollington, Heather Q and Litwin-Kumar, Ashok and Cardona, Albert and Truman, James W and Doe, Chris Q} } @article {65258, title = {A multilayer circuit architecture for the generation of distinct locomotor behaviors in .}, journal = {eLlife}, volume = {8}, year = {2019}, month = {2019 Dec 23}, abstract = {

Animals generate diverse motor behaviors, yet how the same motor neurons (MNs) generate two distinct or antagonistic behaviors remains an open question. Here we characterize larval muscle activity patterns and premotor/motor circuits to understand how they generate forward and backward locomotion. We show that all body wall MNs are activated during both behaviors, but a subset of MNs change recruitment timing for each behavior. We used TEM to reconstruct a full segment of all 60 MNs and 236 premotor neurons (PMNs), including differentially-recruited MNs. Analysis of this comprehensive connectome identified PMN-MN {\textquoteright}labeled line{\textquoteright} connectivity; PMN-MN combinatorial connectivity; asymmetric neuronal morphology; and PMN-MN circuit motifs that could all contribute to generating distinct behaviors. We generated a recurrent network model that reproduced the observed behaviors, and used functional optogenetics to validate selected model predictions. This PMN-MN connectome will provide a foundation for analyzing the full suite of larval behaviors.

}, issn = {2050-084X}, doi = {10.7554/eLife.51781}, author = {Zarin, Aref Arzan and Mark, Brandon and Cardona, Albert and Litwin-Kumar, Ashok and Doe, Chris Q} } @article {49347, title = {MDN brain descending neurons coordinately activate backward and inhibit forward locomotion.}, journal = {eLife}, volume = {7}, year = {2018}, month = {2018 Aug 02}, abstract = {

Command-like descending neurons can induce many behaviors, such as backward locomotion, escape, feeding, courtship, egg-laying, or grooming (we define {\textquoteright}command-like neuron{\textquoteright} as a neuron whose activation elicits or {\textquoteright}commands{\textquoteright} a specific behavior). In most animals it remains unknown how neural circuits switch between antagonistic behaviors: via top-down activation/inhibition of antagonistic circuits or via reciprocal inhibition between antagonistic circuits. Here we use genetic screens, intersectional genetics, circuit reconstruction by electron microscopy, and functional optogenetics to identify a bilateral pair of larval {\textquoteright}mooncrawler descending neurons{\textquoteright} (MDNs) with command-like ability to coordinately induce backward locomotion and block forward locomotion; the former by stimulating a backward-active premotor neuron, and the latter by disynaptic inhibition of a forward-specific premotor neuron. In contrast, direct monosynaptic reciprocal inhibition between forward and backward circuits was not observed. Thus, MDNs coordinate a transition between antagonistic larval locomotor behaviors. Interestingly, larval MDNs persist into adulthood, where they can trigger backward walking. Thus, MDNs induce backward locomotion in both limbless and limbed animals.

}, issn = {2050-084X}, doi = {10.7554/eLife.38554}, author = {Carreira-Rosario, Arnaldo and Zarin, Aref Arzan and Clark, Matthew Q and Manning, Laurina and Fetter, Richard D and Cardona, Albert and Doe, Chris Q} } @article {47135, title = {Even-Skipped(+) interneurons are core components of a sensorimotor circuit that maintains left-right symmetric muscle contraction amplitude.}, journal = {Neuron}, volume = {88}, year = {2015}, month = {2015 Oct 21}, pages = {314-29}, abstract = {

Bilaterally symmetric motor patterns-those in which left-right pairs of muscles contract synchronously and with equal amplitude (such as breathing, smiling,\ whisking, and locomotion)-are widespread throughout the animal kingdom. Yet, surprisingly little is known about the underlying neural circuits. We performed a thermogenetic screen to identify neurons required for bilaterally symmetric locomotion in Drosophila larvae and identified the evolutionarily conserved Even-skipped(+) interneurons (Eve/Evx). Activation or ablation of Eve(+) interneurons disrupted bilaterally symmetric muscle contraction amplitude, without affecting the timing of motor output. Eve(+) interneurons are not rhythmically active and thus function independently of the locomotor CPG. GCaMP6 calcium imaging of Eve(+) interneurons in freely moving larvae showed left-right asymmetric activation that correlated with larval behavior. TEM reconstruction of Eve(+) interneuron inputs and outputs showed that the Eve(+) interneurons are at the core of a sensorimotor circuit capable of detecting and modifying body wall muscle contraction.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2015.09.009}, author = {Heckscher, Ellie S and Zarin, Aref Arzan and Faumont, Serge and Clark, Matthew Q and Manning, Laurina and Fushiki, Akira and Schneider-Mizell, Casey M and Fetter, Richard D and Truman, James W and Zwart, Maarten F and Landgraf, Matthias and Cardona, Albert and Lockery, Shawn R and Doe, Chris Q} }