Friday, November 22, 2024
11/22/2024
PROJECT SUMMARY The overall goal of our NIGMS-funded research program is to identify and characterize the mechanisms that allow individual sensory neurons to sense and respond to defined environmental cues, and to modulate these responses based on experience and context. The lab explores these issues in two independent but related areas. In the first, we study how individual sensory neuron types acquire their specialized sensory cilia morphologies. In the second, we study how the morphologies and functions of sensory neurons are modulated by experience. With R35 funding, we have been able to build synergies between these research areas and to extend our work in unanticipated directions. A first major goal for the upcoming period will be to build on our work in ciliogenic mechanisms to investigate how the organization of neuronal cilia within a sense organ, as well as interciliary contacts, contribute to shaping sensory neuron functions. We previously showed that sensory cilia are stereotypically organized within a head sense organ in C. elegans; the mechanisms that underlie this organization and the functional consequences of this patterning are unknown. We will determine whether an adhesion code regulates interciliary contacts and organization, and explore how these contacts regulate neuronal communication and function. A second major goal will be to investigate how temperature experience reshapes the complex morphologies of the AFD thermosensory neuron pair in C. elegans. The architecture of the AFD sensory endings is regulated by neuronal activity and plays a critical role in the ability of these neurons to adapt and respond to environmental temperature variations. We will exploit our expertise in neuronal cell biology and high-resolution analyses of sensory behaviors and sensory neuron responses to describe how the shape of the AFD sensory endings is modified as a function of the animal’s experience, and how this modification in turn modulates AFD function. A third major goal will be to investigate how the experience of an analog variable such as temperature is translated into graded gene expression changes in a single sensory neuron type in vivo, and how these gene expression changes in turn influence neuronal properties. We plan to establish whether the gene expression pattern in a neuron encodes its temporal activity history, identify the required regulatory mechanisms, and assess the consequences on neuronal functions. Our multifaceted experimental approach will allow us to generate a comprehensive description of how activity and experience intersect with developmental pathways to modify sensory neuron structure and function, thereby generating appropriate behavioral plasticity. This award will also enable us to continue to train the next generation of scientists, to establish new collaborations, and to generate and test innovative and novel hypotheses. Given the conservation of sensory and ciliogenic mechanisms, we expect that findings from this work will be broadly generalizable, and may provide insights into how altered regulation of neuronal structural and functional plasticity leads to disease.
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