Investigating multisensory integration properties in the developing neural network of Xenopus laevis tadpoles

Brown University, Providence RI

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Abstract

? DESCRIPTION (provided by applicant): Neural circuits form the basis of all interactions with the outside world as well as internal thoughts. Specifically, the neural circuits used in sensory processing are critical for perception and understanding of the external environment. This research seeks to determine the synaptic and cellular underpinnings of multisensory processing, commonly referred to as multisensory integration, and to understand the development of the neural circuits involved in multisensory integration. Much is already known about the behavioral outcomes and the psychophysical properties of multisensory tasks and the underlying neuronal activity, but a detailed cellular description of this process is lacking. This research will fill a wide gap in our understanding of the synaptic and circuit level mechanisms underlying the development of neural circuits mediating multisensory processing in the vertebrate brain. Multisensory integration may underlie several brain disorders, including autism spectrum disorders and sensory processing disorders. This research will provide baseline information on the synaptic, cellular and neural network events underlying development of sensory integration and lay the foundation for future work that is disorder-specific. The tadpole preparation allows easy access to the developing larvae, which provides simple and robust disorder-relevant manipulations. Since this research will further our understanding of the neural circuitry, future research will build upon this work to understand the underlying synaptic and cellular mechanisms of autism and other neurodevelopmental disorders. The model organism used in this proposal, Xenopus laevis tadpoles, provides a few unique advantages over other species. First, the experimental preparation contains the intact neural circuitry for multisensory integration, including the sensory organs, allowing the examination of a complete circuit with multiple techniques. Second, the small size and ease of breeding provides the resources to analyze a phenomenon at multiple levels, including single cell electrophysiology, network calcium imaging, behavioral assays, environmental manipulations, and computational modeling. This proposal has two specific aims that will address the questions underlying the development of the neural circuitry underlying multisensory integration. Aim 1. Assessment of cellular properties of multisensory integration. These experiments will focus on the roles of NMDA type glutamate receptors and dendritic integration on multisensory processing, as well as plasticity at different developmental stages. Aim 2. Understand the functional development of multisensory integration. These experiments will assess multisensory plasticity using long term multisensory experience manipulation and network calcium imaging.