Two fundamental questions regarding the neural basis of sensation are how stimuli are encoded in the nervous system and how animals discriminate between stimuli. In chemosensory systems there is a diversity of chemoreceptors that matches the diversity in chemical space. Volatile chemicals, or odors, are often represented in the periphery by a combinatorial code of neuronal activity. By contrast, the more simple qualities of soluble tasted chemicals, such as bitter and sweet, are sensed by anatomically distinct populations of cells that drive stereotyped behaviors. The nematode Caenorhabditis elegans senses and discriminates between many soluble and volatile chemicals, and exhibits plasticity in chemosensory behavior. This thesis addresses the cellular and molecular mechanisms underlying C. elegans chemosensory behaviors through genetic analysis, quantitative analysis of behavior and measurement of neuronal activity.
C. elegans discriminates among certain food-related odors by mechanisms that require multiple olfactory cell types. In this study, animals with only one type of functional neuron are shown to discriminate between some odors. Therefore, cell-intrinsic mechanisms may participate in certain kinds of odor discrimination, in addition to combinatorial mechanisms.
Some chemosensory cues drive innate behaviors by activating a hardwired, "labeled-line" circuit connecting sensory input to motor output. However, this thesis shows that C. elegans AWC olfactory neurons that drive attraction can also drive avoidance in some contexts. cGMP and PKC signaling in olfactory neurons reverses odor preference by altering neurotransmission at the first sensory synapse. Therefore, a hardwired circuit can generate opposite behavioral outcomes through alternative modes of synaptic transmission.
Further analysis of cGMP signaling mutants revealed that neuronal cGMP signaling is involved not only in chemosensory behaviors in C. elegans but also in regulating adaptive behavioral responses to osmotic stress. These results provide a striking parallel to the role of cGMP signaling in vertebrate water homeostasis. The adaptive response to osmotic stress has been mapped to a set of candidate mechanosensitive neurons. These neurons are distinct from those that sense mechanical touch stimuli along the body or the nose. Thus mechanosensation and osmosensation may arise from segregated neuronal pathways, which could facilitate discrimination between the different types of mechanical stimuli.