Andreas Schoofs

Selection of motor programs for suppressing food intake and inducing locomotion in the Drosophila brain.

This study reveals that a cluster of neurons expressing the neuropeptide hugin transmit inputs from higher brain centers to motor centers, thereby regulating feeding and locomotion in fruit fly larvae.

Synaptic transmission parallels neuromodulation in a central food-intake circuit

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: http://dx.doi.org/10.7554/eLife.16799.001

From behavior to fictive feeding: anatomy, innervation and activation pattern of pharyngeal muscles of Calliphora vicina 3rd instar larvae.

A description of the muscles and nerves involved in feeding of larval Calliphora vicina is given as a prerequisite to establish fictive feeding patterns recorded from the isolated central nervous system. Feeding Diptera larvae show a repetitive sequence of pro- and retraction of the cephalopharyngeal skeleton (CPS), elevation and depression of the mouth hooks and food ingestion. The corresponding pharyngeal muscles are protractors, mouth hook elevators and depressors, the labial retractor and cibarial dilator muscles. These muscles are innervated by the prothoracic accessory nerve (PaN), maxillary nerve (MN) and antennal nerve (AN) as shown electrophysiologically by recording action potentials from the respective nerve that correlate to post-synaptic potentials on the muscles. All three nerves show considerably more complex branching patterns than indicated in the literature. Extracellular recordings from the stumps of PaN, MN and AN connected to an isolated CNS show spontaneous rhythmic motor patterns that reflect the feeding sequence in intact larvae. Variability of the feeding pattern observed in behavioral experiments is also evident from the level of motor output from an isolated CNS. The data obtained from Calliphora will facilitate electrophysiological investigations dealing with the genetic background of feeding behavior in Drosophila larvae.

The brain can eat: establishing the existence of a central pattern generator for feeding in third instar larvae of Drosophila virilis and Drosophila melanogaster.

To establish the existence of a central pattern generator for feeding in the larval central nervous system of two Drosophila species, the gross anatomy of feeding related muscles and their innervation is described, the motor units of the muscles identified and rhythmic motor output recorded from the isolated CNS. The cibarial dilator muscles that mediate food ingestion are innervated by the frontal nerve. Their motor pathway projects from the brain through the antennal nerves, the frontal connectives and the frontal nerve junction. The mouth hook elevator and depressor system is innervated by side branches of the maxillary nerve. The motor units of the two muscle groups differ in amplitude: the elevator is always activated by a small unit, the depressor by a large one. The dorsal protractors span the cephalopharyngeal skeleton and the body wall hence mediating an extension of the CPS. These muscles are innervated by the prothoracic accessory nerve. Rhythmic motor output produced by the isolated central nervous system can simultaneously be recorded from all three nerves. The temporal pattern of the identified motor units resembles the sequence of muscle contractions deduced from natural feeding behavior and is therefore considered as fictive feeding. Phase diagrams show an almost identical fictive feeding pattern is in both species.

Serotonergic pathways in the Drosophila larval enteric nervous system.

The enteric nervous system is critical for coordinating diverse feeding-related behaviors and metabolism. We have characterized a cluster of four serotonergic neurons in Drosophila larval brain: cell bodies are located in the subesophageal ganglion (SOG) whose neuronal processes project into the enteric nervous system. Electrophysiological, calcium imaging and behavioral analyses indicate a functional role of these neurons in modulating foregut motility. We suggest that the axonal projections of this serotonergic cluster may be part of a brain-gut neural pathway that is functionally analogous to the vertebrate vagus nerve.

Localization of Motor Neurons and Central Pattern Generators for Motor Patterns Underlying Feeding Behavior in Drosophila Larvae.

Motor systems can be functionally organized into effector organs (muscles and glands), the motor neurons, central pattern generators (CPG) and higher control centers of the brain. Using genetic and electrophysiological methods, we have begun to deconstruct the motor system driving Drosophila larval feeding behavior into its component parts. In this paper, we identify distinct clusters of motor neurons that execute head tilting, mouth hook movements, and pharyngeal pumping during larval feeding. This basic anatomical scaffold enabled the use of calcium-imaging to monitor the neural activity of motor neurons within the central nervous system (CNS) that drive food intake. Simultaneous nerve- and muscle-recordings demonstrate that the motor neurons innervate the cibarial dilator musculature (CDM) ipsi- and contra-laterally. By classical lesion experiments we localize a set of CPGs generating the neuronal pattern underlying feeding movements to the subesophageal zone (SEZ). Lesioning of higher brain centers decelerated all feeding-related motor patterns, whereas lesioning of ventral nerve cord (VNC) only affected the motor rhythm underlying pharyngeal pumping. These findings provide a basis for progressing upstream of the motor neurons to identify higher regulatory components of the feeding motor system.

The thoracic muscular system and its innervation in third instar Calliphora vicina Larvae. I. Muscles of the pro- and mesothorax and the pharyngeal complex

An anatomical description is given by the muscles in the pro‐ and mesothorax, and those associated with the feeding apparatus (cephalopharyngeal skeleton, CPS) that participate in feeding behavior in third instar Calliphora larvae. The body wall muscles in the pro‐ and mesothoracic segments are organized in three layers: internal, intermedial, and external. The muscles were labeled with roman numerals according to the nomenclature in use for the abdominal segments. Muscles associated with the CPS are labeled according to their function. The prothorax bears five pairs of lateral symmetrically longitudinal segmental body wall muscles and lacks the transversal muscle group present in the mesothorax and abdominal segments. Additionally, four pairs of intersegmental muscles project from the prothorax to the second, fourth, and fifth segment. The mesothorax bears 15 pairs of segmental longitudinal and 18 pairs of transversal muscles. The accessory pharyngeal muscles span the CPS and the cuticle. Three pairs of protractors and retractors and two pairs of mouth hook accessors (MHAC) exist, which move the CPS relative to the body. The pharyngeal muscles are exclusively attached to the structures of the CPS. The mouth hook elevators and depressors, which mediate the hooks rotation are attached to the ventral arm of the CPS and project to a dorsal (elevators) or ventral (depressors) protuberance of the mouth hooks. The cibarial dilator muscles (CDM) span the dorsal arms of the CPS and the dorsal surface of the esophagus and mediate food ingestion. The labial retractors (LRs) lack antagonists and project from the ventral surface of the CPS to the unpaired labium. Contractions of these muscles open the mouth cavity. J. Morphol. 271:960–968, 2010.

Serotonergic network in the subesophageal zone modulates the motor pattern for food intake in Drosophila

The functional organization of central motor circuits underlying feeding behaviors is not well understood. We have combined electrophysiological and genetic approaches to investigate the regulatory networks upstream of the motor program underlying food intake in the Drosophila larval central nervous system. We discovered that the serotonergic network of the CNS is able to set the motor rhythm frequency of pharyngeal pumping. Pharmacological experiments verified that modulation of the feeding motor pattern is based on the release of serotonin. Classical lesion and laser based cell ablation indicated that the serotonergic neurons in the subesophageal zone represent a redundant network for motor control of larval food intake.

Neuroscience: Hunger Pangs in the Fly Brain.

Which neurons in the brain become engaged when the body is deprived of food? A new study addresses this question using the vinegar fly Drosophila melanogaster, examining a group of neurons in the brain that show alterations in neural activity when flies are satiated or starved.

The thoracic muscular system and its innervation in third instar Calliphora vicina Larvae. II. Projection patterns of the nerves associated with the pro- and mesothorax and the pharyngeal complex.

We describe the anatomy of the nerves that project from the central nervous system (CNS) to the pro‐ and mesothoracic segments and the cephalopharyngeal skeleton (CPS) for third instar Calliphora larvae. Due to the complex branching pattern we introduce a nomenclature that labels side branches of first and second order. Two fine nerves that were not yet described are briefly introduced. One paired nerve projects to the ventral arms (VAs) of the CPS. The second, an unpaired nerve, projects to the ventral surface of the cibarial part of the esophagus (ES). Both nerves were tentatively labeled after the structures they innervate. The antennal nerve (AN) innervates the olfactory dorsal organ (DO). It contains motor pathways that project through the frontal connectives (FC) to the frontal nerve (FN) and innervate the cibarial dilator muscles (CDM) which mediate food ingestion. The maxillary nerve (MN) innervates the sensory terminal organ (TO), ventral organ (VO), and labial organ (LO) and comprises the motor pathways to the mouth hook (MH) elevator, MH depressor, and the labial retractor (LR) which opens the mouth cavity. An anastomosis of unknown function exists between the AN and MN. The prothoracic accessory nerve (PaN) innervates a dorsal protractor muscle of the CPS and sends side branches to the aorta and the bolwig organ (BO) (stemmata). In its further course, this nerve merges with the prothoracic nerve (PN). The architecture of the PN is extremely complex. It innervates a set of accessory pharyngeal muscles attached to the CPS and the body wall musculature of the prothorax. Several anastomoses exist between side branches of this nerve which were shown to contain motor pathways. The mesothoracic nerve (MeN) innervates a MH accessor and the longitudinal and transversal body wall muscles of the second segment. J. Morphol. 271:969–979, 2010.