This research seeks to understand how the activities of individual neurons combine together in defined circuits to generate the behavioral output of the nervous system. The behavior to be studied is the copulatory behavior of the nematode Caenorhabditis elegans male. Using reconstruction from serial section electron micrographs, the complete pattern of synaptic connectivity has been determined for the region of the male nervous system that generates copulatory behavior. This neuropil contains the processes of 175 neurons connected by some 8000 synapses (4000 chemical, 4000 electrical). The wiring diagram, which consists of a complex network of interactions, serves as the basis for examining the role of individual neurons in generating behavioral output. C. elegans male copulatory behavior consists of a series of sub-behaviors executed according to sensory input to allow the male to insert hardened spicules into the hermaphrodite vulva and transfer sperm. Neurons have been identified that by their pattern of connectivity appear to be associated with each of these sub-behaviors. We will test our hypothesis for the function of these neurons by eliminating them from the circuit by cell killing. The behavioral deficit that results will indicate the role of the neuron in the circuit. An important question to be addressed is whether the network contains circuits or modules dedicated to specific sub-behaviors or instead have a distributed type of architecture, generating multiple behaviors as alternative modes of function of the whole. To assess the relative importance of chemical and electrical communication within the network, the neurotransmitters utilized will be determined. Chemical neurotransmission will be blocked using mutants or through cell-specific RNAi approaches to reveal the function of the electrical circuit. The wiring diagram contains a repeated network motif in which a sensory neuron and an interneuron are connected both directly and via a pair of interneurons that is common to all, forming a triangular circuit. This motif may have one of several possible influences on the function of the network, depending on whether the common neuron pair is excitatory or inhibitory on the interneuron. In order to determine the functional characteristics of this motif, the neurotransmitter and receptor types in the circuit will be determined and the result of activating or inhibiting the circuit will be determined.

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Focusing on a region of the nervous system of the invertebrate genetic model animal Caenorhabditis elegans where the complete pattern of synaptic connectivity has been recently determined, the function of individual neurons in a completely defined neural network will be examined in order to understand how circuits in the nervous system generate complex animal behavior.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Hagan, Ann A
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Albert Einstein College of Medicine
Schools of Medicine
United States
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Barrios, Arantza; Nurrish, Stephen; Emmons, Scott W (2008) Sensory regulation of C. elegans male mate-searching behavior. Curr Biol 18:1865-71
Jia, Lingyun; Emmons, Scott W (2006) Genes that control ray sensory neuron axon development in the Caenorhabditis elegans male. Genetics 173:1241-58
Lipton, Jonathan; Kleemann, Gunnar; Ghosh, Rajarshi et al. (2004) Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple invertebrate. J Neurosci 24:7427-34