Project Summary This proposal seeks to understand the synaptic and circuit-level mechanisms underlying multisensory integration in the developing optic tectum. In order to correctly perceive and navigate its environment, an organism must integrate multiple types of sensory information containing different spatial and tem- poral characteristics. This process requires that the neural circuits that mediate multisensory integration are wired together appropriately during early brain development. However, the cellular mechanisms underlying the function and development of brain circuits mediating multisensory integration remain poorly understood. In the vertebrate brain, one primary locus for multisensory integration is the optic tectum, or its mamma- lian homologue, the superior colliculus. It functions to integrate visual and other sensory information, and transform this into orienting behavior. We have developed a novel and powerful experimental preparation to study the development of multisensory integration in the optic tectum using Xenopus laevis tadpoles. This preparation has an advantage over other more complex preparations such as owl tectum or mammalian superior colliculus in that it allows us to take an integrative approach in which we combine multiple levels of analysis ranging from single neurons to behavior, using a variety of tech- niques such as single-cell recordings in vivo and ex vivo, high-speed Ca++ imaging of networks of tectal neurons, visually guided behavior, and genetic alteration of neural activity. In the first aim, we will test the hypothesis that the dynamics of the balance between excitation and in- hibition determine the temporal window for multisensory integration. In the second aim we test the hy- pothesis that inhibition promotes and constrains the emergence of functional subtypes of multisensory neurons over development. In the third aim we test the hypothesis that the integrative properties and input architecture of tectal dendrites shapes multisensory interactions in tectal neurons and is responsi- ble for the principle of inverse effectiveness. We also test whether this principle extends to multisenso- ry-evoked behavior. These results will enhance our general understanding of the development and merging of neural cir- cuits and systems. Since many neurodevelopmental disorders such as autism, schizophrenia, dyslexia and ADHD are accompanied by dysfunctions in sensory integration, the findings from these experi- ments will better allow us to understand how these processes may go awry in neurodevelopmental dis- orders. !