Identification of neurons controlling orientation behavior in the Drosophila melanogaster larva

En este estudio hemos aprovechado la simplicidad numérica del sistema nervioso de la larva de la Drosophila melanogaster para identificar las neuronas responsables que dirigen sus movimientos de acuerdo a ciertas sustancias químicas (quimiotaxis). Con este propósito, hemos realizado un amplio rastreo conductual utilizando el sistema Gal4/UAS para expresar en subpoblaciones de neuronas genéticamente definidas una toxina silenciadora de la sinapsis. Hemos identificado una línea Gal4 (NP4820) perteneciente al subgrupo de neuronas del ganglio subesofágico (GSO) del cerebro de la larva involucrada en la organización de modalidades conductuales específicas subyacentes al comportamiento orientativo. Las larvas desprovistas de neuronas marcadas-NP4820 funcionales se vieron afectadas en cuanto a la correcta transición de una trayectoria recta a un movimiento de rastreo/giro respecto a su experiencia sensorial. Activar las neuronas remotamente fue suficiente para iniciar la maniobra de rastreo/giro. Este efecto puede generalizarse a otras modalidades sensoriales a parte del olfato, sugiriendo así el GSO como una región del cerebro esencial para seleccionar y ejecutar acciones. Utilizando la misma estrategia buscamos neuronas responsables de la orientación en campos electrostáticos. Hemos demostrado que las larvas de Drosophila migran hacia el cátodo, basándose en maniobras de rastreo/giro para alinearse al campo eléctrico. Además, hemos identificado neuronas eletrosensoriales localizadas en el órgano terminal de la larva. Analysis funcionale ha demostrado que su actividad neuronal depende de la orientación y amplitud del campo, sustentando así la habilidad de la larva para alinearse al campo eléctrico local. Hemos revelado la existencia de una nueva modalidad sensorial en la Drosophila melanogaster y evidencia que el campo eléctrico representa un estímulo biológicamente relevante.Detecting sensory stimuli and converting them into behavioral output is the essential function of nervous systems. In this study we took advantage of the numerical simplicity of the nervous system of the Drosophila melanogaster larva to find neurons underlying orientation behavior to chemical cues (chemotaxis). To this aim we performed a behavioral screen using the Gal4/UAS system to express a synaptic silencing toxin in genetically defined subpopulations of neurons. We identified a Gal4 line (NP4820) covering a subgroup of neurons in the suboesophageal ganglion of the larval brain to be involved in the organization of the specific behavioral modes underlying orientation behaviors. Larvae devoid of functional NP4820-labeled neurons were impaired in the correct transition from run- to casts/turn- mode. Remotely activating the neurons was sufficient to initiate a cast/turn maneuver. The effect could be generalized to other sensory modalities than olfaction, suggesting the SOG as a brain region generally essential for action selection and execution. Using the same approach we searched for neurons underlying orientation in a static electric field. We found that Drosophila larvae robustly migrate to the cathode, making use of cast/turn maneuvers to align to the field. Moreover, our behavioral screen revealed electrosensory neurons located in the larval terminal organ. Functional imaging showed that their neural activity is tuned to the orientation and amplitude of the field, underlying the ability of the larva to align with the local electric field. Our findings revealed the existence of a novel sensory modality in Drosophila melanogaster and evidence that electric fields represent a biologically relevant stimulus

Role of the subesophageal zone in sensorimotor control of orientation in Drosophila larva

Chemotaxis is a powerful paradigm to investigate how nervous systems represent and integrate changes in sensory signals to direct navigational decisions. In the Drosophila melanogaster larva, chemotaxis mainly consists of an alternation of distinct behavioral modes: runs and directed turns. During locomotion, turns are triggered by the integration of temporal changes in the intensity of the stimulus. Upon completion of a turning maneuver, the direction of motion is typically realigned toward the odor gradient. While the anatomy of the peripheral olfactory circuits and the locomotor system of the larva are reasonably well documented, the neural circuits connecting the sensory neurons to the motor neurons remain unknown. We combined a loss-of-function behavioral screen with optogenetics-based clonal gain-of-function manipulations to identify neurons that are necessary and sufficient for the initiation of reorientation maneuvers in odor gradients. Our results indicate that a small subset of neurons residing in the subesophageal zone controls the rate of transition from runs to turns-a premotor function compatible with previous observations made in other invertebrates. After having shown that this function pertains to the processing of inputs from different sensory modalities (olfaction, vision, thermosensation), we conclude that the subesophageal zone operates as a general premotor center that regulates the selection of different behavioral programs based on the integration of sensory stimuli. The present analysis paves the way for a systematic investigation of the neural computations underlying action selection in a miniature brain amenable to genetic manipulations.M.L. acknowledges funding from the Spanish Ministry of Science and Innovation (MICINN, BFU2008-00362, BFU2009-07757-E/BMC, and BFU2011-26208), the EMBL/CRG Systems Biology Program, and a Marie Curie Reintegration Grant (PIRG02-GA-2007-224791). J.W.T. was supported by the Howard Hughes Medical Institute. I.T. acknowledges funding from the Marie Curie FP7 Programme through FLiACT (ITN

Dynamical feature extraction at the sensory periphery guides chemotaxis

Behavioral strategies employed for chemotaxis have been described across phyla, but the sensorimotor basis of this phenomenon has seldom been studied in naturalistic contexts. Here, we examine how signals experienced during free olfactory behaviors are processed by first-order olfactory sensory neurons (OSNs) of the Drosophila larva. We find that OSNs can act as differentiators that transiently normalize stimulus intensity—a property potentially derived from a combination of integral feedback and feed-forward regulation of olfactory transduction. In olfactory virtual reality experiments, we report that high activity levels of the OSN suppress turning, where as low activity levels facilitate turning. Using a generalized linear model, we explain how peripheral encoding of olfactory stimuli modulates the probability of switching from a run to a turn. Our work clarifies the link between computations carried out at the sensory periphery and action selection underlying navigation in odor gradients.This work was supported by the EU project “Marie-Curie Action: Initial Training Networks” (EC FP7-PEOPLE-2011-ITN, grant number 289941)