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Rhythmic behaviors (e.g., walking, breathing, and chewing) are produced by central pattern generator (CPG) circuits. These circuits are highly dynamic due to a multitude of input they receive from hormones, sensory neurons, and modulatory projection neurons. Such inputs not only turn CPG circuits on and off, but they adjust their synaptic and cellular properties to select behaviorally relevant outputs that last from seconds to hours. Similar to the contributions of fully identified connectomes to establishing general principles of circuit function and flexibility, identified modulatory neurons have enabled key insights into neural circuit modulation. For instance, while bath-applying neuromodulators continues to be an important approach to studying neural circuit modulation, this approach does not always mimic the neural circuit response to neuronal release of the same modulator. There is additional complexity in the actions of neuronally-released modulators due to: (1) the prevalence of co-transmitters, (2) local- and long-distance feedback regulating the timing of (co-)release, and (3) differential regulation of co-transmitter release. Identifying the physiological stimuli (e.g., identified sensory neurons) that activate modulatory projection neurons has demonstrated multiple “modulatory codes” for selecting particular circuit outputs. In some cases, population coding occurs, and in others circuit output is determined by the firing pattern and rate of the modulatory projection neurons. The ability to perform electrophysiological recordings and manipulations of small populations of identified neurons at multiple levels of rhythmic motor systems remains an important approach for determining the cellular and synaptic mechanisms underlying the rapid adaptability of rhythmic neural circuits.
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This content will become publicly available on July 26, 2026
Control of walking direction by descending and dopaminergic neurons in Drosophila
Summary Animals need to fine-control the speed and direction of locomotion to navigate complex and dynamic environments. To achieve this, they integrate multimodal sensory inputs with their internal drive to constantly adjust their motor output. This integration involves the interplay of neuronal populations across different hierarchical levels along the sensorimotor axis – from sensory, central, and modulatory neurons in the brain to descending neurons and motor networks in the nerve cord. Here, we characterize two populations of neurons that control distinct aspects of walking on different hierarchical levels inDrosophila. First, we usein-vivoelectrophysiological recordings to demonstrate that moonwalker descending neurons (MDN) integrate antennal touch to drive changes in walking direction from forward to backward. Second, we establish DopaMeander as an important component in the control of forward walking through a combination of optogenetic activation, silencing, connectomics, andin-vivorecordings. These dopaminergic modulatory neurons drive forward walking with increased turning, and the activity of individual neurons is correlated with ipsiversive turning. Hence, MDN and DopaMeander control opposite regimes of walking on different hierarchical levels. Computational models reveal that their activity predicts key parameters of spontaneous walking. Moreover, we find that both MDN and DopaMeander are gated out during flight. This suggests that neuronal populations across levels of control are modulated by the behavioral state to minimize cross-talk between motor programs.
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- Award ID(s):
- 2015317
- PAR ID:
- 10627518
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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