Functional modularity and multisensory convergence in the lateral cortex of the mouse inferior colliculus

项目总结

Project Summary Projections carrying somatosensory information converge upon several nuclei within the auditory system. While the exact function of these connections is unknown, they can contribute to and modify the pathological sound percepts present in tinnitus patients. Though current treatments attempt to exploit these pathways to ameliorate tinnitus symptoms, very little is known about the their anatomy and physiology. The lateral cortex of the inferior colliculus is one such auditory structure that receives heavy input from both brainstem and cortical somatosensory nuclei. Though this structure has long been implicated in multisensory integration, the termination patterns of inputs to the lateral cortex are segregated into distinct streams: the somatosensory inputs target areas of high-density GAD67 staining, known as modules, while the auditory inputs terminate in extramodular areas. Given this mismatch between functional and anatomical data, the goal of this proposal is to reveal the circuitry and mechanisms underlying multisensory convergence in the lateral cortex. Two main hypotheses will be explored: 1) cells within modular and extramodular regions of the lateral cortex communicate with one another, potentially producing multisynaptic multisensory convergence, and 2) the dendrites of individual cells in modular or extramodular regions extend into the complementary region, thus receiving both auditory and somatosensory input. These hypotheses will be tested in brain slices from the GAD67-GFP mouse, in which modules can be visualized under blue light. Cells in modular and extramodular regions of the lateral cortex will be recorded from and potential presynaptic partners throughout the structure will be stimulated using laser photostimulation of caged glutamate. Inhibitory and excitatory input maps will be constructed to determine whether inputs for a given cell arise from modular areas, extramodular areas, or both. The degree of communication between cells in modular and extramodular areas will be quantified. To further explore the functional differences between modular and extramodular areas, the amount of spontaneous inhibitory and excitatory input to cells in both regions will be determined. To ascertain whether individual cells integrate both somatosensory and auditory information, somatosensory projections from the dorsal column nuclei will be pre-labeled with a red-shifted opsin, C1V1. This pathway will be stimulated with a green laser, and the auditory pathway from the central nucleus of the inferior colliculus will be stimulated via laser uncaging with a UV laser. The synaptic properties of each pathway will be examined; if cells responding to both stimuli are found, the interstimulus interval will be systematically altered to determine the effect of timing on the bimodal response. The experiments outlined above will further characterize the somatosensory inputs and intrinsic circuitry of the lateral cortex, which could have important implications for both normal and pathological hearing. Furthermore, these experiments may reveal generalizable principles regarding integration of multisensory inputs at the level of a single cell.