Input-specific induction of cerebellar long-term depression does not require presynaptic alteration.

Abstract

In cerebellar long-term depression (LTD), conjunctive stimulation of parallel fiber (PF) and climbing fiber (CF) inputs to a Purkinje neuron result in a selective depression of PF-Purkinje neuron synaptic strength. This system is attractive for the study of neuronal information storage, both because of its duration and because it demonstrates input specificity. The mechanisms underlying input specificity in this system are not known, but they could involve presynaptic alterations, postsynaptic alterations, or some combination of both. To allow for an unambiguous analysis of postsynaptic processes, an LTD induction protocol has been developed using cultured cerebellar cells in which pulses of quisqualate and direct Purkinje neuron depolarization replace PF and CF stimulation, respectively. Input specificity is retained in this reduced system. When multiple, nonoverlapping quisqualate application sites are used, LTD is confined to those sites that are stimulated during depolarization. This property of LTD induction is also preserved under conditions where both spontaneous and evoked neurotransmitter releases are reduced or eliminated, indicating that postsynaptic alterations are sufficient to confer input specificity. Input-specific LTD may also be induced by local application of a protein kinase C (PKC) activator (1-oleoyl-2-acetylglycerol) together with direct Purkinje neuron depolarization, suggesting that input-specific LTD results from the conjunction of a spatially broad Ca signal mediated by Purkinje neuron depolarization, together with a spatially constrained PKC-activating signal mediated by quisqualate application.