Properties of 4 Hz stimulation‐induced parallel fiber–Purkinje cell presynaptic long‐term plasticity in mouse cerebellar cortex in vivo

Cerebellar parallel fiber–Purkinje cell ( PF – PC ) long‐term synaptic plasticity is important for the formation and stability of cerebellar neuronal circuits, and provides substrates for motor learning and memory. We previously reported both presynaptic long‐term potentiation ( LTP ) and long‐term depression ( LTD ) in cerebellar PF – PC synapses in vitro . However, the expression and mechanisms of cerebellar PF – PC synaptic plasticity in the cerebellar cortex in vivo are poorly understood. In the present study, we studied the properties of 4 Hz stimulation‐induced PF – PC presynaptic long‐term plasticity using in vivo the whole‐cell patch‐clamp recording technique and pharmacological methods in urethane‐anesthetised mice. Our results demonstrated that 4 Hz PF stimulation induced presynaptic LTD of PF – PC synaptic transmission in the intact cerebellar cortex in living mice. The PF – PC presynaptic LTD was attenuated by either the N ‐methyl‐D‐aspartate receptor antagonist, D‐aminophosphonovaleric acid, or the group 1 metabotropic glutamate receptor antagonist, JNJ 16259685, and was abolished by combined D‐aminophosphonovaleric acid and JNJ 16259685, but enhanced by inhibition of nitric oxide synthase. Blockade of cannabinoid type 1 receptor activity abolished the PF – PC LTD and revealed a presynaptic PF – PC LTP . These data indicate that both endocannabinoids and nitric oxide synthase are involved in the 4 Hz stimulation‐induced PF – PC presynaptic plasticity, but the endocannabinoid‐dependent PF – PC presynaptic LTD masked the nitric oxide‐mediated PF – PC presynaptic LTP in the cerebellar cortex in urethane‐anesthetised mice.