@article {69608, title = {Serotonergic modulation of swallowing in a complete fly vagus nerve connectome.}, journal = {Curr Biol}, year = {2024}, month = {2024 Sep 05}, abstract = {

How the body interacts with the brain to perform vital life functions, such as feeding, is a fundamental issue in physiology and neuroscience. Here, we use a whole-animal scanning transmission electron microscopy volume of Drosophila to map the neuronal circuits that connect the entire enteric nervous system to the brain via the insect vagus nerve at synaptic resolution. We identify a gut-brain feedback loop in which Piezo-expressing mechanosensory neurons in the esophagus convey food passage information to a cluster of six serotonergic neurons in the brain. Together with information on food value, these central serotonergic neurons enhance the activity of serotonin receptor 7-expressing motor neurons that drive swallowing. This elemental circuit architecture includes an axo-axonic synaptic connection from the glutamatergic motor neurons innervating the esophageal muscles onto the mechanosensory neurons that signal to the serotonergic neurons. Our analysis elucidates a neuromodulatory sensory-motor system in which ongoing motor activity is strengthened through serotonin upon completion of a biologically meaningful action, and it may represent an ancient form of motor learning.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2024.08.025}, url = {https://doi.org/10.1016/j.cub.2024.08.025}, author = {Schoofs, Andreas and Miroschnikow, Anton and Schlegel, Philipp and Zinke, Ingo and Schneider-Mizell, Casey M and Cardona, Albert and Pankratz, Michael J} } @article {67310, title = {Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in Drosophila.}, journal = {eLife}, volume = {10}, year = {2021}, month = {2021 Jun 04}, abstract = {

Neuroendocrine systems in animals maintain organismal homeostasis and regulate stress response. Although a great deal of work has been done on the neuropeptides and hormones that are released and act on target organs in the periphery, the synaptic inputs onto these neuroendocrine outputs in the brain are less well understood. Here, we use the transmission electron microscopy reconstruction of a whole central nervous system in the larva to elucidate the sensory pathways and the interneurons that provide synaptic input to the neurosecretory cells projecting to the endocrine organs. Predicted by network modeling, we also identify a new carbon dioxide-responsive network that acts on a specific set of neurosecretory cells and that includes those expressing corazonin (Crz) and diuretic hormone 44 (Dh44) neuropeptides. Our analysis reveals a neuronal network architecture for combinatorial action based on sensory and interneuronal pathways that converge onto distinct combinations of neuroendocrine outputs.

}, issn = {2050-084X}, doi = {10.7554/eLife.65745}, author = {H{\"u}ckesfeld, Sebastian and Schlegel, Philipp and Miroschnikow, Anton and Schoofs, Andreas and Zinke, Ingo and Haubrich, Andr{\'e} N and Schneider-Mizell, Casey M and Truman, James W and Fetter, Richard D and Cardona, Albert and Pankratz, Michael J} } @article {49583, title = {Convergence of monosynaptic and polysynaptic sensory paths onto common motor outputs in a feeding connectome.}, journal = {eLife}, volume = {7}, year = {2018}, month = {2018 Dec 11}, abstract = {

We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of larvae. Input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS. Output neurons consist of feeding motor, serotonergic modulatory and neuroendocrine neurons. Monosynaptic connections from a set of sensory synaptic compartments cover the motor, modulatory and neuroendocrine targets in overlapping domains. Polysynaptic routes are superimposed on top of monosynaptic connections, resulting in divergent sensory paths that converge on common outputs. A completely different set of sensory compartments is connected to the mushroom body calyx. The mushroom body output neurons are connected to interneurons that directly target the feeding output neurons. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.

}, issn = {2050-084X}, doi = {10.7554/eLife.40247}, author = {Miroschnikow, Anton and Schlegel, Philipp and Schoofs, Andreas and Hueckesfeld, Sebastian and Li, Feng and Schneider-Mizell, Casey M and Fetter, Richard D and Truman, James W and Cardona, Albert and Pankratz, Michael J} } @article {48045, title = {Synaptic transmission parallels neuromodulation in a central food-intake circuit.}, journal = {eLife}, year = {2016}, month = {2016 Nov 15}, abstract = {

NeuromedinU is a potent regulator of food intake and activity in mammals. In\ Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the\ Drosophila\ larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.

}, doi = {10.7554/eLife.16799}, author = {Schlegel, Philipp and Texada, Michael J and Miroschnikow, Anton and Schoofs, Andreas and H{\"u}ckesfeld, Sebastian and Peters, Marc and Schneider-Mizell, Casey M and Lacin, Haluk and Li, Feng and Fetter, Richard D and Truman, James W and Cardona, Albert and Pankratz, Michael J} }