MDN brain descending neurons coordinately activate backward and inhibit forward locomotion

Abstract

Command-like descending neurons can induce many behaviors, such as backward locomotion, escape, feeding, courtship, egg-laying, or grooming (we define ‘command-like neuron’ as a neuron whose activation elicits or ‘commands’ 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 Drosophila larval ‘mooncrawler descending neurons’ (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.

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

“…Recently, a serial section transmission electron microscopy (TEM) volume of the entire first instar larval CNS was generated (Ohyama et al 2015). To date, however, only a small fraction of PMNs and MNs have been reconstructed (Heckscher et al 2015; Fushiki et al 2016; Zwart et al 2016; Carreira-Rosario et al 2018). Here, we identify and reconstruct all differentiated MNs in segment A1, which can be used as a proxy for other abdominal segments.…”

“…We are interested in understanding how the Drosophila larva executes multiple behaviors, in particular forward versus backward locomotion (Carreira-Rosario et al 2018). Are there different motor neurons used in each behavior?…”

“…Body wall muscles are innervated by approximately 60 MNs per segment, consisting of 28 left/right pairs that typically each innervate one muscle, and whose neuromuscular junctions have b ig boutons, therefore also called type-I b MNs; two pair of type-Is ( s mall bouton) MNs that innervate large groups of dorsal or ventral muscles; three type II ventral unpaired median MNs that provide octopaminergic innervation to most muscles; and one or two type III insulinergic MNs innervating muscle 12 (Gorczyca et al 1993; Landgraf et al 1997; Hoang and Chiba 2001; Landgraf et al 2003; Choi et al 2004; Mauss et al 2009; Koon et al 2011; Koon and Budnik 2012; Zarin and Labrador 2017). All MNs in segment A1 have been identified by backfills from their target muscles (Landgraf et al 1997; Landgraf et al 2003; Mauss et al 2009), and several have been shown to be rhythmically active during larval locomotion, but only a few of their premotor inputs have been described (Kohsaka et al 2014; Heckscher et al 2015; Fushiki et al 2016; Hasegawa et al 2016; Zwart et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018). Some excitatory PMNs are involved in initiating activity in their target MNs (Fushiki et al 2016; Hasegawa et al 2016; Zwart et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018), while some inhibitory PMNs limit the duration of MN activity (Kohsaka et al 2014; MacNamee et al 2016; Schneider-Mizell et al 2016) or produce intrasegmental activity offsets (Zwart et al 2016).…”

“…All MNs in segment A1 have been identified by backfills from their target muscles (Landgraf et al 1997; Landgraf et al 2003; Mauss et al 2009), and several have been shown to be rhythmically active during larval locomotion, but only a few of their premotor inputs have been described (Kohsaka et al 2014; Heckscher et al 2015; Fushiki et al 2016; Hasegawa et al 2016; Zwart et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018). Some excitatory PMNs are involved in initiating activity in their target MNs (Fushiki et al 2016; Hasegawa et al 2016; Zwart et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018), while some inhibitory PMNs limit the duration of MN activity (Kohsaka et al 2014; MacNamee et al 2016; Schneider-Mizell et al 2016) or produce intrasegmental activity offsets (Zwart et al 2016). Interestingly, some PMNs are active specifically during forward locomotion or backward locomotion (Kohsaka et al 2014; Heckscher et al 2015; Fushiki et al 2016; Hasegawa et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018).…”

“…Some excitatory PMNs are involved in initiating activity in their target MNs (Fushiki et al 2016; Hasegawa et al 2016; Zwart et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018), while some inhibitory PMNs limit the duration of MN activity (Kohsaka et al 2014; MacNamee et al 2016; Schneider-Mizell et al 2016) or produce intrasegmental activity offsets (Zwart et al 2016). Interestingly, some PMNs are active specifically during forward locomotion or backward locomotion (Kohsaka et al 2014; Heckscher et al 2015; Fushiki et al 2016; Hasegawa et al 2016; Takagi et al 2017; Carreira-Rosario et al 2018). In addition, there are six pair of proprioceptor neurons in each abdominal segment (ddaE, ddaD, vpda, dmd1, dbd and vbd).…”