Classical eyeblink conditioning in glutamate receptor subunit δ2 mutant mice is impaired in the delay paradigm but not in the trace paradigm

In mice lacking glutamate receptor subunit delta2 (GluR delta2(-/-) mice), cerebellar long-term depression (LTD) at the parallel fibre-Purkinje cell synapses is disrupted. Unlike the cerebellar LTD-deficient mice previously used for eyeblink conditioning, however, the abnormalities of the GluR delta2(-/-) mice are restricted to the cerebellar cortex. In delay eyeblink conditionings (interstimulus interval of 252 and 852 ms), in which the conditioned stimulus (CS) overlaps temporally with a coterminating unconditioned stimulus (US), GluR delta2(-/-) mice are severely impaired in learning, strongly supporting the hypothesis that cerebellar cortical LTD is essential for delay conditioning. In the trace paradigm, in which a stimulus-free trace interval of 500 ms intervened between the CS and US, GluR delta2(-/-) mice learned as successfully as wild-type mice, indicating that cerebellar LTD is not necessary for trace conditioning. Thus, the present study has revealed a cerebellar LTD-independent learning in eyeblink conditioning.