Long-term depression (LTD)

LTD (Long-term depression) is seen in the cerebral and hippocampus cortex where it can occur alongside Long-term depression and in the cerebellum in that LTP is never seen. Induction of Long-term depression in the cerebellum at the pf–PC synapse needs coincident Ca²⁺ influx into the Purkinje cell and activation of AMPA and metabotropic glutamate receptors at the synapse. The Ca²⁺ influx is provided through the huge depolarization due to climbing fiber activity that opens voltage-dependent Ca²⁺ channels. The receptors are activated through the release of glutamate from the parallel fibers. The last cause of the synaptic depression is desensitization of the AMPA receptors in Figure brought about through their phosphorylation through protein kinase C and nitric oxide-activated protein kinase G.

Figure: Cellular events in cerebellar LTD. Glu, Glutamate; AMPAR, AMPA receptor; mGluR1, type  1 metabotropic glutamate receptor; Gq, G protein; NO, nitric oxide;  NOS, nitric oxide  synthase; PKG, protein kinase  G; PKC, protein kinase  C; GC, guanylyl cyclase; PLC, phospholipase C; DAG, diacylglycerol; PC, Purkinje cell; pf, parallel  fiber; cf, climbing fiber.