RESUMEN
The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is important for synaptic plasticity and nervous system development and function. We have used genetic and electrophysiological methods to demonstrate that NMR-1, a Caenorhabditis elegans NMDA-type ionotropic glutamate receptor subunit, plays a role in the control of movement and foraging behavior. nmr-1 mutants show a lower probability of switching from forward to backward movement and a reduced ability to navigate a complex environment. Electrical recordings from the interneuron AVA show that NMDA-dependent currents are selectively disrupted in nmr-1 mutants. We also show that a slowly desensitizing variant of a non-NMDA receptor can rescue the nmr-1 mutant phenotype. We propose that NMDA receptors in C. elegans provide long-lived currents that modulate the frequency of movement reversals during foraging behavior.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/genética , Locomoción/fisiología , Receptores de N-Metil-D-Aspartato/genética , Transmisión Sináptica/fisiología , Animales , Animales Modificados Genéticamente , Electrofisiología , Eliminación de Gen , Expresión Génica/fisiología , Interneuronas/química , Interneuronas/fisiología , Aprendizaje por Laberinto/fisiología , Potenciales de la Membrana/fisiología , Datos de Secuencia Molecular , Mutagénesis/fisiología , Fenotipo , Receptores AMPA , Receptores de Glutamato/análisis , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/análisis , Receptores de N-Metil-D-Aspartato/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
In almost all nervous systems, rapid excitatory synaptic communication is mediated by a diversity of ionotropic glutamate receptors. In Caenorhabditis elegans, 10 putative ionotropic glutamate receptor subunits have been identified, a surprising number for an organism with only 302 neurons. Sequence analysis of the predicted proteins identified two NMDA and eight non-NMDA receptor subunits. Here we describe the complete distribution of these subunits in the nervous system of C. elegans. Receptor subunits were found almost exclusively in interneurons and motor neurons, but no expression was detected in muscle cells. Interestingly, some neurons expressed only a single subunit, suggesting that these may form functional homomeric channels. Conversely, interneurons of the locomotory control circuit (AVA, AVB, AVD, AVE, and PVC) coexpressed up to six subunits, suggesting that these subunits interact to generate a diversity of heteromeric glutamate receptor channels that regulate various aspects of worm movement. We also show that expression of these subunits in this circuit is differentially regulated by the homeodomain protein UNC-42 and that UNC-42 is also required for axonal pathfinding of neurons in the circuit. In wild-type worms, the axons of AVA, AVD, and AVE lie in the ventral cord, whereas in unc-42 mutants, the axons are anteriorly, laterally, or dorsally displaced, and the mutant worms have sensory and locomotory defects.
Asunto(s)
Proteínas de Caenorhabditis elegans , Regulación de la Expresión Génica/fisiología , Proteínas del Helminto/metabolismo , Proteínas de Homeodominio/metabolismo , Sistema Nervioso/metabolismo , Subunidades de Proteína , Receptores de Glutamato/biosíntesis , Animales , Animales Modificados Genéticamente , Axones/metabolismo , Conducta Animal , Caenorhabditis elegans , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Fluorescentes Verdes , Proteínas del Helminto/genética , Proteínas del Helminto/farmacología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/farmacología , Interneuronas/citología , Interneuronas/metabolismo , Proteínas Luminiscentes/genética , Neuronas Motoras/citología , Neuronas Motoras/metabolismo , Trastornos del Movimiento/genética , Músculos/citología , Músculos/metabolismo , Mutación , Fenotipo , Filogenia , Receptores AMPA , Receptores de Glutamato/genética , Receptores de N-Metil-D-Aspartato/biosíntesis , Receptores de N-Metil-D-Aspartato/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Trastornos de la Sensación/genética , Homología de Secuencia de AminoácidoRESUMEN
How simple neuronal circuits control behavior is not well understood at the molecular or genetic level. In Caenorhabditis elegans, foraging behavior consists of long, forward movements interrupted by brief reversals. To determine how this pattern is generated and regulated, we have developed novel perturbation techniques that allow us to depolarize selected neurons in vivo using the dominant glutamate receptor mutation identified in the Lurcher mouse. Transgenic worms that expressed a mutated C. elegans glutamate receptor in interneurons that control locomotion displayed a remarkable and unexpected change in their behavior-they rapidly alternated between forward and backward coordinated movement. Our findings suggest that the gating of movement reversals is controlled in a partially distributed fashion by a small subset of interneurons and that this gating is modified by sensory input.