Neural circuits driving larval locomotion in Drosophila

Abstract

More than 30 years of studies into Drosophila melanogaster neurogenesis have revealed fundamental insights into our understanding of axon guidance mechanisms, neural differentiation, and early cell fate decisions. What is less understood is how a group of neurons from disparate anterior-posterior axial positions, lineages and developmental periods of neurogenesis coalesce to form a functional circuit. Using neurogenetic techniques developed in Drosophila it is now possible to study the neural substrates of behavior at single cell resolution. New mapping tools described in this review, allow researchers to chart neural connectivity to better understand how an anatomically simple organism performs complex behaviors.

Keywords: Locomotion; Locomotor circuits; Multisensory integration; Navigation; Neurodevelopment; Sensorimotor; Wave propagation.

Fig. 1

Muscles and motor neurons that drive various locomotor behaviors. Schematic of Drosophila larva side view, anterior to left. Mouthhooks far left, black; CNS with anterior brain lobes and ventral nerve cord, grey. Nerves contain sensory input from abdominal segments (small circles) and motor neuron output to muscles (red/green/blue rectangles). The red/green/blue territories represent muscle functional groups containing ~ 10 individual muscles each: red is dorsal longitudinal muscles, green is transverse muscles, and blue is ventral longitudinal muscles. Some of these individual muscles are shown in the same color code in more posterior segments. This larva shows only seven segments for clarity; wild type larvae contain three thoracic segments and eight abdominal segments

Fig. 2

Muscles and motor neurons that drive various locomotor behaviors. a Larval locomotor behaviors. b Abdominal motor neurons and muscles in a single hemisegment. Only the type Ib motor neurons are shown (big bouton/single muscle target). Longitudinal muscles are light red, transverse muscles are darker red. Anterior to left; ventral midline, dashed line; dorsal midline at top of panel. c Cross-section schematic of abdominal neuropil; surrounding cell bodies are not shown. Motor dendrites target the dorsal (most internal) domain, sensory axons target ventral (most superficial) domains, with the exception of proprioceptive axons that target an intermediate domain. Ventral midline separating left/right sides, dashed line

Fig. 3

Local and projection interneurons. Examples of local and projection interneurons. There are also descending interneurons with somata in the brain, SEZ, thoracic, or upper abdominal segments (not shown). All panels show a single hemi-segment for clarity (A1 left), although the neurons are bilateral and present in more posterior abdominal segments as well. Midline, arrowhead. (a, b) Local interneurons. A27j is an ipsilateral local interneuron that confines its pre- and post-synaptic arbors to the hemisegment containing its soma [103]. A08e3 is a contralateral local interneuron that projects a process across the midline [16]. Contralateral local interneurons typically have pre-synaptic outputs contralateral to the soma, and post-synaptic inputs on ipsilateral arbors. (c–e) Projection interneurons. A05q is a contralateral projection interneuron that extends anteriorly multiple segments but does not reach the brain [85]. A08s is a contralateral projection interneuron that extends anteriorly to the brain [16]. A02o, also called the “wave” neuron, has a contralateral projection that terminates in the thorax and/or SEZ [82]. Typically, projection interneuron have pre-synaptic outputs at the anterior terminus of the ascending projection, and post-synaptic inputs on the local arbors

Fig. 4

Circuit motifs used in larval locomotion. a Circuits leading to sequential longitudinal/transverse muscle contraction. Motor neurons innervating both longitudinal and transverse muscle groups (“longitudinal” and “transverse” motor neurons, respectively) receive similar excitatory premotor input, but the motor neurons specifically innervating transverse muscles also receive inhibitory input which leads to a delay in the initiation of transverse muscle contraction. b Circuits that limit the length of motor neuron activity. The PMSI A02b/A02m inhibitory premotor neurons limit the length of motor neuron firing. GABAergic A27j/A31k may also perform this function based on their neurotransmitter and connectivity, but have not yet been functionally characterized. Dbd sensory neurons are thought to be stretch receptors [104], hence activated by muscle relaxation in the segment they are tiling and/or by muscle contraction in the adjacent segments. If so, it is likely that A02a and A02l fire after A02b/A02m and A27j/A31k premotor neurons to remove the inhibition from motor neurons after their target muscles are relaxed, preparing them for the next round of firing. c Circuits that promote smooth progression of the muscle contraction wave during forward locomotion. The A27h premotor neuron activates motor neuron firing in a segment, while also activating the inhibitor GDL neuron in the next most anterior segment, which leads to a delay in motor activity necessary for smooth wave progression. d Circuits that promote larval rolling. Only the local VNC circuit is shown for clarity. Sensory input leads to activation of the Goro “command-like” neuron that is necessary and sufficient for rolling behavior