How does signaling pathway affect long-term depression in purkinje cells?
When parallel fibers (PFs) are active, they release the neurotransmitter glutamate onto the dendrites of Purkinje cells. This activates AMPA-type receptors, which are ligand gated ion channels, and causes a small EPSP that briefly depolarizes the Pirkinje cell. The glutamate released by PFs activates metabotropic glutamate receptors, which stimulates phospholipase C to produce IP3 and DAG. When the PF synapses alone are active, these intracellular signals are insufficient to open IP3 receptors or to stimulate PKC.
LTD is induced when PF synapses are activated at the same time as glutamatergic climber fiber synapses that also innervate purkinke cells. The climbing fiber synapses produce large EPSPs that strongly depolarize the membrane potential of the Purkinje cell. This depolarization allows Ca to enter the Purkinje cell via voltage-gated Ca channels. When both synapses are simultaneously avtivated, the rise in intracellular Ca concentration caused by the climbing fiber synapse enhances the sensitivity of IP3 receptors to the IP3 profuced by PF synapses and allows the IP3 receptors within the Purkinje cell to open, This releases Ca from the endoplasmic reticulum and further elevates Ca concentrations. The Ca and the IP3 can then activates PKC to commence LTD. This results in the AMPA-type receptors producing a smaller depolarization when they are activated