Afferent proprioceptive signaling in Drosophila larvae
openNINDS - National Institute of Neurological Disorders and Stroke
ABSTRACT
Proprioception is the sense that allows animals to monitor their body position and movements; proprioceptive
deficits lead to severe challenges in moving and maintaining posture. Proprioceptive feedback passes
through local pathways targeting motor circuits, where proprioception adjusts ongoing movements, as well as
projection pathways to the brain, where proprioception is used to learn and plan future actions. The
fundamental differences between projection and local pathways remain largely unknown. Our long-term
goal is to understand proprioceptive circuit activity during natural animal behavior, with a focus on the roles
played by genetically defined cell types. The objective of this proposal is to characterize the fundamental
differences between projection and local pathways. We focus on second-order neurons, CNS neurons that
receive direct input from proprioceptive sensory neurons. We will specifically address the following questions:
Does the brain receive minimally processed proprioceptive stimulus information or integrated representations
of specific stimulus features? Is information presented to the brain in a behaviorally state-dependent manner?
Does the brain receive different types of information in comparison to local circuitry?
We use Drosophila larvae as a highly tractable model to study proprioception. This proposal leverages
two major technical innovations: (1) CRASH2p microscopy, which enables volumetric imaging of neural
dynamics in intact, freely moving, and behaving larvae, and (2) connectomics, which facilitates the
comprehensive reconstruction of synaptic connections between second-order neurons and their synaptic
partners.
Based on preliminary data, we will test the central hypothesis that local and projection second-order
proprioceptive neurons differentially integrate and process naturally occurring self-movement stimuli. We test
this hypothesis using complementary in-depth (functional, Aim 1) and in-breadth (anatomical, Aim 2)
approaches.
The proposed research is significant because it will provide two advances that, to date, remain out of
reach in other models. First, it will provide a comprehensive anatomical understanding of the full complement
of second-order proprioceptive neurons and the networks in which they are embedded. Second, it will
produce first-of-its-kind knowledge of the activity of second-order proprioceptive neurons in intact animals
performing multiple behaviors and determine the role of a specific type of proprioceptor in shaping that
activity. Thus, our work is expected to provide a new conceptual framework for understanding how various
second-order neurons integrate and process proprioceptive information, as well as how the brain senses
proprioceptive stimuli.
Up to $603K
health research