Parallel Fiber Stimulation in the Mouse Cerebellar Cortex In Vivo

38 The parallel fibers (PFs) in the cerebellar cortex extend several millimeters along a folium in the 39 medio-lateral direction. The PFs are orthogonal to and cross several parasagittal zones defined by 40 the olivocerebellar and corticonuclear pathways and the expression of molecular markers on 41 Purkinje cells (PCs). The functions of these two organizations remain unclear, including 42 whether the bands respond similarly or differentially to PF input. Using flavoprotein imaging in 43 the anesthetized mouse in vivo, this study demonstrates that high frequency PF stimulation, 44 which activates a beam-like response at short latency, also evokes patches of activation at long 45 latencies. These patches consist of increased fluorescence along the beam at latencies of 20-25 s 46 with peak activation at 35 s. The long-latency patches are completely blocked by the mGluR 1 47 antagonist, LY367385. Conversely, the AMPA and NMDA glutamate receptor antagonists, 48 DNQX and APV, have little effect. Organized in parasagittal bands the long-latency patches 49 align with zebrin II-positive PC stripes. Additional Ca 2+ imaging demonstrates that the patches 50 reflect increases in intracellular Ca 2+. Both the PLCβ inhibitor, U73122, and ryanodine receptor 51 inhibitor, ryanodine, completely block the long-latency patches, indicating that the patches are 52 due to Ca 2+ release from intracellular stores. Robust, mGluR 1-dependent long-term potentiation 53 (LTP) of the patches is induced using a high frequency PF stimulation conditioning paradigm 54 that generates LTP of PF-PC synapses. Therefore, the parasagittal bands, as defined by the 55 molecular compartmentalization of PCs, respond differentially to PF inputs via mGluR 1-56 mediated release of internal Ca 2+. 57 58