Presynaptic inhibition selectively suppresses leg proprioception in behavingDrosophila

Abstract

The sense of proprioception is mediated by internal mechanosensory neurons that detect joint position and movement. To support a diverse range of functions, from stabilizing posture to coordinating movements, proprioceptive feedback to limb motor control circuits must be tuned in a context-dependent manner. How proprioceptive feedback signals are tuned to match behavioral demands remains poorly understood. Using calcium imaging in behavingDrosophila, we find that the axons of position-encoding leg proprioceptors are active across behaviors, whereas the axons of movement-encoding leg proprioceptors are suppressed during walking and grooming. Using connectomics, we identify a specific class of interneurons that provide GABAergic presynaptic inhibition to the axons of movement-encoding proprioceptors. These interneurons are active during self-generated but not passive leg movements and receive input from descending neurons, suggesting they are driven by predictions of leg movement originating in the brain. Predictively suppressing expected proprioceptive feedback provides a mechanism to attenuate reflexes that would otherwise interfere with voluntary movement.

GABA Increases Sensory Transmission In Monkeys

“…Furthermore, our proposed perspective provides a new control mechanism for descending control of afferent activity. In this regard, recent evidence suggests that cortico-spinal tracts can modulate primary afferent inputs through PAD [19,26,32]. Finally, our data highlights the extent to which PAD impacts the production of movement even at the hand.…”

Divergent neural circuits for proprioceptive and exteroceptive sensing of theDrosophilaleg

“…In support of this mechanism, we found several inhibitory upstream partners of claw and hook axons (Figure S3). We also showed in a recent study that hook axons are presynaptically inhibited during voluntary movement 29 . In addition to direct feedback onto somatosensory axons, proprioceptive feedback is also likely tuned via context-dependent inhibition of downstream pathways.…”

“…We focused our reconstruction efforts on these FeCO axons because they project to the front left neuromere of the VNC (also referred to as left T1 or T1L), the region of the Drosophila VNC with the most complete information about leg sensorimotor circuits. All of the motor neurons controlling the muscles of the front left leg and their presynaptic partners have been previously identified and reconstructed in FANC 26,27 , and prior neurophysiological recordings of FeCO axons and their downstream targets were made in the same region 14,15,24,25,28,29 . Unfortunately, leg sensory axons are among the most difficult neurons to reconstruct in the available VNC connectomes, likely due to rapid cell-death that begins when the legs are separated from the VNC during sample preparation.…”

“…The strongest input comes from 9A neurons, which are primarily presynaptic to hook axons (Figure S3C-D). Recent work found that a subset of 9A neurons suppress expected proprioceptive feedback during voluntary movement such as walking or grooming 29 .…”

Sensorimotor delays constrain robust locomotion in a 3D kinematic model of fly walking

“…We propose that fly motor circuits may encode predictions of future joint positions, so the fly may generate motor commands that account for motor neuron and muscle delays. Consistent with this hypothesis, Dallmann et al (2023) recently found that descending motor commands from the brain excite GABAergic interneurons in the VNC that inhibit velocity-encoding proprioceptors. Thus, some proprioceptive feedback signals from the fly leg are predictively suppressed during self-generated movements.…”