Caudate nucleus is critically involved in trace eyeblink conditioning.

The basal ganglia are a collection of brain regions involved with motor planning and initiation. The major site of cortical and thalamic input into the basal ganglia network is the striatum, which includes a differentiated caudate nucleus (CN) and the putamen in rabbits. Trace eyeblink conditioning (EBC) is a forebrain-dependent associative learning task in which a stimulus-free time interval separates the presentation of a behaviorally neutral conditioned stimulus (CS) and a behaviorally salient unconditioned stimulus. We investigated whether the CN is essential for acquisition of trace EBC and whether learning-related changes in neuronal activity occur in the caudate nucleus during trace EBC. Bilateral lesions of the CN in rabbits prevent acquisition of trace EBC. In separate cohorts of rabbits, single-unit recordings showed that medium spiny neurons from regions shown to be critical by lesions display strong responses to the CS, especially in the initial days of training before acquisition. Cholinergic interneurons, or tonically active neurons, become responsive to the CS and show dramatic firing rate changes during the trace interval after learning criterion has been met. These data demonstrate that the CN is required for and involved in trace EBC.