Genetic and electrophysiological analyses of the control of locomotion by ionotropic glutamate receptors in Caenorhabditis elegans

A fundamental problem in neuroscience is to understand how behavior is controlled. I have taken a combined genetic, behavioral, and electrophysiological approach to address this problem at both the molecular and neuronal network level in the simple soil nematode Caenorhabditis elegans. Specifically, I have characterized the role of a single class of molecules, the ionotropic glutamate receptors (iGluRs) in regulating locomotion.; In order to understand how iGluRs regulate cell excitability, I developed reliable patch-clamp electrophysiological techniques that allowed me to characterize the locomotory role of three individual receptor subunits. In particular, I have focused on the role of the NMDA type glutamate receptor subunit NMR-1 and the non-NMDA subunits GLR-1 and GLR-2 in a single interneuron (AVA) of the neuronal network that controls locomotion.; The NMDA type glutamate receptor subunit NMR-1 is required for slow, long-lasting currents in AVA. Genetic analysis of nmr-1 showed that it regulates the duration and direction of movement by, likely, integrating sensory information. NMR-1 is also required for osmotic avoidance behaviors. It participates in osmotic avoidance with non-NMDA receptors that contain GLR-1 and GLR-2 subunits. In contrast to NMDA receptors, GLR-1 and GLR-2 are necessary for large, rapidly-activating and desensitizing currents. In addition, GLR-1 and GLR-2 are required for a specific form of tactile avoidance that NMR-1 is not required for, despite the fact that all three receptor subunits are expressed in AVA and receive sensory input from the same sensory neuron, ASH. We have shown that GLR-1 and NMR-1 are not localized at the same synapses and thus we propose a model for polymodal signaling that involves the release of different amounts of neurotransmitter and the differential activation of glutamate receptors.; By combining electrophysiological analysis with detailed genetic analyses of locomotion, I have linked gene function and behavior. These studies provide valuable insights into how behavior is controlled at the molecular and neuronal network level. In particular, these studies have uncovered a mechanism of polymodal signaling that requires the differential activation of ionotropic glutamate receptors that may prove useful in understanding other forms of polymodal signaling, such as pain sensation and perception in vertebrates.