Defining a minimal computational unit for cerebellar long-term depression

In cerebellar long-term depression (LTD), conjunctive stimulation of parallel and climbing fiber inputs to a Purkinje neuron (PN) results in a selective depression of parallel fiber-PN synaptic strength. A similar phenomenon may be induced in the cultured PN when glutamate pulses and PN depolarization, which mimic the effects of parallel and climbing fibers, respectively, are coapplied. Here, we show that LTD can be induced in two very reduced preparations of the postsynaptic neuron; an acutely dissociated preparation and a perforated outside-out macropatch of dendritic membrane. LTD in these preparations retains properties of that seen in an intact cultured PN in that it is not induced by either glutamate pulses or depolarization alone and requires calcium influx, mGluR activation, and PKC activation for induction. As both of these preparations lack dendritic spine compartments, these findings suggest that the associative nature of LTD induction does not require this level of morphological organization.