ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

Abstract

Animals generate diverse motor behaviors, yet how the same motor neurons generate distinct behaviors remains an open question.Drosophilalarvae have multiple behaviors – e.g. forward crawling, backward crawling, self-righting and escape – and all of the body wall motor neurons (MNs) driving these behaviors have been identified. Despite impressive progress in mapping larval motor circuits, the role of most motor neurons in locomotion remains untested, the majority of premotor neurons (PMNs) remain to be identified, and a full understanding of proprioceptor-PMN-MN connectivity is missing. Here we report a comprehensive larval proprioceptor-PMN-MN connectome; describe individual muscle/MN phase activity during both forward and backward locomotor behaviors; identify PMN-MN connectivity motifs that could generate muscle activity phase relationships, plus selected experimental validation; identify proprioceptor-PMN connectivity that provides an anatomical explanation for the role of proprioception in promoting locomotor velocity; and identify a new candidate escape motor circuit. Finally, we generate a recurrent network model that produces the observed sequence of motor activity, showing that the identified pool of premotor neurons is sufficient to generate two distinct larval behaviors. We conclude that different locomotor behaviors can be generated by a specific group of premotor neurons generating behavior-specific motor rhythms.

Identifying neural substrates of competitive interactions and sequence transitions during mechanosensory responses in Drosophila

“…sensory processing, decisions, motor control, sequence generation) from the exploration of all the neurons in this nervous system to specific neurons and brain regions. Therefore this database is a prerequisite for the comprehensive circuit studies underlying sensorimotor decisions and action sequences during behavioral responses to a mechanical sensory cues as the candidate neurons can be used as starting points for circuit mapping and analysis by combining the results of silencing behavioral genetics experiments with the different methods available in Drosophila larva to relate structure and function of neuronal circuits: EM reconstruction, optogenetics, electrophysiology, calcium imaging, immunohistochemistry and modeling [10,21,[23][24][25][26][27][28][29][30].…”

“…By matching the light microscopy images to the EM images, we identified the A03a5 and A02d neurons. A03a5 [27,29,39] based on connectivity data is a pre-motor neuron as it synapses on multiple motor neurons, while the A02d (Fig 4I) is a glutamatergic neuron that receives input from proprioceptive neurons and synapses on premotor neurons [27]. It can be observed in the ethogram (Fig 4B) that the decrease in Bending probability in this line is due to both the decrease in Bending occurring as the first action upon stimulus onset as well as the second action upon transition from the Bend compared to the control.…”

Reconstruction of motor control circuits in adultDrosophilausing automated transmission electron microscopy

“…Monosynaptic sensory-to-motor neuron connectivity is infrequent in the larval Drosophila nervous system (Zarin et al, 2019), but more frequent in other adult insects (Burrows, 1996). One possibility is that direct sensory feedback in adults is key for control of segmented limbs, enabling precise and adaptive limb movements.…”

Central processing of leg proprioception inDrosophila

“…Neurons arising from the same neuroblast produce a similar set of molecules and innervate similar nerve tracts in both larvae and adults (Birkholz et al, 2015;Lacin and Truman, 2016)-are they also functionally similar? Several central neurons in the larval VNC, such as the Basin neurons, have been implicated in relaying mechanosensory or proprioceptive input to motor circuits (Heckscher et al, 2015;Jovanic et al, 2016;Mark et al, 2019;Ohyama et al, 2015;Zarin et al, 2019). Basin neurons, like adult 9A neurons, descend from lineage 9 and receive inputs from larval chordotonal neurons-do adult 9A neurons also receive nociceptive input or synapse onto motor neurons?…”