Module 10: Figure long-term depression
The proposed role of the inositol 1,4,5-trisphosphate (InsP3)/Ca2+ signalling cassette in coincident detection cerebellar long-term depression (LTD).
The climbing fibre, which innervates the proximal dendrites (grey inset), depolarizes the entire dendritic tree to activate voltage-operated channels (VOCs), resulting in an elevation of intracellular Ca2+ that spreads through the dendrites and into the spines (dashed yellow arrows). The parallel fibres that directly innervate the spines release glutamate, which acts on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and metabotropic type 1 glutamate receptors (mGluR1s). The latter produce inositol 1,4,5-trisphosphate (InsP3) that acts on the InsP3 receptor (I), which functions as a coincident detector by responding to the simultaneous presentation of Ca2+ and InsP3-released Ca2+ from the internal store into the spine, where it acts to inhibit the AMPA receptor.