Long-term Depression of Glutamate Currents in Cultured Cerebellar Purkinje Neurons Does Not Require Nitric Oxide Signalling.

Abstract

Cerebellar long-term depression (LTD) is produced when conjunctive stimulation of parallel fibre (PF) and climbing fibre (CF) inputs to a Purkinje neuron (PN) results in a prolonged decrease in the strength of the PF - PN synapse. In cultured PNs, LTD may be induced by substituting depolarization of the PN and iontophoretic glutamate pulses for CF and PF stimulation, respectively, allowing an unambiguous analysis of post-synaptic processes (Linden et al., Neuron, 7, 81 - 89, 1991). Recent studies have suggested that release of the newly described second messenger, nitric oxide, in the cerebellar molecular layer, is necessary for LTD produced in the slice preparation by PF/CF conjunctive stimulation (Shibuki and Okada, Nature, 349, 326 - 328, 1991) or PF/depolarization conjunctive stimulation (Crepel and Jaillard, NeuroReport, 1, 133 - 136, 1990). We report that LTD of glutamate currents produced without synaptic stimulation in cultured PNs is unaffected by reagents that stimulate (sodium nitroprusside) or inhibit (haemoglobin, NG-nitro-l-arginine) nitric oxide signalling.