Serotonergic modulation of walking inDrosophila

Abstract

16To navigate complex environments, animals must generate highly robust, yet flexible, locomotor 17 behaviors. For example, walking speed must be tailored to the needs of a particular 18 environment: Not only must animals choose the correct speed and gait, they must also rapidly 19 adapt to changing conditions, and respond to sudden and surprising new stimuli. 20Neuromodulators, particularly the small biogenic amine neurotransmitters, allow motor circuits 21 to rapidly alter their output by changing their functional connectivity. Here we show that the 22 serotonergic system in the vinegar fly, Drosophila melanogaster, can modulate walking speed in 23 a variety of contexts and in response to sudden changes in the environment. These multifaceted 24 roles of serotonin in locomotion are differentially mediated by a family of serotonergic receptors 25 with distinct activities and expression patterns. 27walk forwards, backwards, and upside down, navigate complex terrains, and rapidly recover 31 after injury [1][2][3][4][5][6][7][8][9]. To achieve this wide range of behaviors, insects regulate their global walking 32 speed and kinematic parameters, allowing them to modify stereotyped gaits as needed [3,5-33 7,9,10]. Because overlapping sets of motor neurons and muscles are recruited for all of these 34 behaviors, animals must be able to rapidly modulate the circuit dynamics that control locomotor 35 parameters [11-13] (reviewed in [14]). 36As with limbed vertebrates, most insects use multi-jointed legs to walk [8,10,[15][16][17]. Locomotor 37 circuits that orchestrate these complex gaits are located in the ventral nerve cord (VNC), a 38 functional analogue of the vertebrate spinal cord that includes three pairs of thoracic 39 neuromeres (T1, T2, and T3) that coordinate the movements of the three pairs of thoracic legs 40 [1][2][3][4][5][6][7][8][9][18][19][20]. The insect VNC receives descending commands from the brain and sends motor 41 output instructions via motor neurons to peripheral musculature [3,[5][6][7]9,10,19]. Leg motor 42 neuron dendrites innervate the leg neuropils within the VNC and their axons exit the VNC to 43 synapse onto muscles in the appendages [11][12][13]21,22]. Sensory neurons, which convey 44 proprioceptive and tactile information, project axons from the appendages to the VNC by these 45 same fiber tracts, where they arborize in the leg neuropils [14,23,24] ( Figure 1A). Notably, the 46 VNC is capable of executing coordinated leg motor behaviors, such as walking and grooming, 48 drive the coordinated flexion and extension of each leg joint and, therefore, walking gaits 49 [8,10,17,20,26]. 50Numerous studies have shown that sensory input from the legs are required for robust 51 and stereotyped locomotor patterns, regulating both the timing and magnitude of locomotor 52 activity and also facilitating coordination between legs [6,8,10,12,[27][28][29]. However, sensory 53 feedback cannot be the only means for tuning locomotion: mutation of proprioceptive receptors 54 or even deafferenting limbs d...

Central processing of leg proprioception in Drosophila

“…Instead, 10Bα neurons drive pauses in walking behavior. Previous behavioral experiments found that flies will stop walking when they sense the ground vibrating (Fabre et al, 2012;Howard et al, 2019)-10Bα neurons may mediate this stopping via vibration-sensitive inputs from the FeCO. If true, this would imply that the FeCO functions as both a proprioceptive and exteroceptive organ.…”

“…Behavioral studies of walking flies demonstrate that vibration of the substrate can cause flies to stop walking (Fabre et al, 2012;Howard et al, 2019). To determine if 10Bα neurons could drive this pausing behavior, we optogenetically activated 10Bα neurons in tethered, intact flies walking on a spherical treadmill (Fig.…”

Collective motion as a distinct behavioural state of the individual

“…Most notable are the biogenic amines (e.g. Serotonin, a prominent bio-amine, was recently reported to inhibit walking behaviour in Drosophila ; Howard et al, 2019). Hence, it may well be that the (spatial and temporal) immediate social environment affects biogenic amine levels, and these in turn modulate the walking-related behavioural kinematics manifested in the different behavioural states.…”

Motor neuron boutons remodel through membrane blebbing

“…The DVGlut-LexA 79 driver was derived from the pCaSpeR VGlut >> LexA construct 80 by removing the FRT cassette with KpnI restriction enzymes. Transgenic lines were generated by standard P-element-mediated transformation procedures in a yw background.…”