Disrupted topography of the acquired trace-conditioned eyeblink responses in guinea pigs after suppression of cerebellar cortical inhibition to the interpositus nucleus

Trace conditioning of the eyeblink reflex, a form of associative motor learning in which presentations of the conditioned stimulus (CS) and the unconditioned stimulus (US) are separated in time by a silent trace interval, requires intact forebrain structures such as the hippocampus and medial prefrontal cortex. Recently, increased learning-related activities have also been observed in specific cerebellar cortical area such as the lobule of HVI during this conditioning task. To date, however, it remains controversial how the cerebellar cortex contributes to trace eyeblink conditioning. In the present study, we addressed this issue by reversibly suppressing the cerebellar cortical inhibition via microinjections of the GABAA receptor antagonist bicuculline methiodide (BICM) into the interpositus nucleus of guinea pigs. We showed that, in the well-trained guinea pigs, the BICM administrations failed to abolish the acquired trace-conditioned eyeblink responses (CRs). Although the acquired trace CRs were mostly retained, their peak latencies were shortened and their peak amplitudes diminished as evidenced by only half of the spared trace CRs preserving the topography of adaptive peak latencies or middle-/high-peak amplitudes. In the same animals, the acquired trace CRs were abolished by microinjections of the GABAA receptor agonist muscimol and were unaffected by microinjections of the artificial cerebrospinal fluid. Furthermore, we demonstrated that with concurrent BICM-induced suppression of the cerebellar cortical inhibition and presentations of the tone CSs in the guinea pigs receiving unpaired conditioning training, CR-like eyeblink responses were not generated. Altogether, these results support the hypothesis that GABAergic neurotransmission from cerebellar cortex to the interpositus nucleus may participate in regulating the expression of acquired trace CRs.