DENDRITIC EXCITABILITY MICROZONES AND OCCLUDED LONG-TERM DEPRESSION AFTER CLASSICAL-CONDITIONING OF THE RABBITS NICTITATING-MEMBRANE RESPONSE

We made intradendritic recordings in Purkinje cells (n = 164) from par asaggital slices of cerebellar lobule HVI obtained from rabbits given paired presentations of tone and periorbital electrical stimulation (c lassical conditioning, n = 27) or explicitly unpaired presentations of tone and periorbital stimulation (control, n = 16). Purkinje cell den dritic membrane excitability, assessed by the current required to elic it local dendritic calcium spikes, increased significantly in slices f rom animals that received classical conditioning. In contrast, membran e potential, input resistance, and amplitude of somatic and dendritic spikes were not different in slices from animals given paired or expli citly unpaired stimulus presentations. The location of cells with low thresholds for local dendritic calcium spikes suggested that there are specific sites for learning-related changes within lobule HVI. These areas may correspond to learning ''microzones'' and are consistent wit h locations of learning-related in vivo changes in Purkinje cell activ ity. Application of 4-aminopyridine, an antagonist of the rapidly inac tivating potassium current I-A, reduced the threshold for dendritic sp ikes in slices from naive animals to levels found in slices from train ed animals. In cells where thresholds for eliciting parallel fiber-sti mulated Purkinje cell excitatory postsynaptic potentials (EPSPs) were measured, levels of parallel fiber stimulation required to elicit a 6- mV EPSP as well as a 4-mV EPSP (n = 30) and a Purkinje cell spike (n = 56) were found to be significantly lower in slices from paired animal s than unpaired controls. A classical conditioning procedure was simul ated in slices of lobule HVI by pairing a brief, high-frequency train of parallel fiber stimulation (8 pulses, 100 Hz) with a brief, lower f requency train of climbing fiber stimulation (3 pulses, 20 Hz) to the same Purkinje cell. Following paired stimulation of the parallel and c limbing fibers, Purkinje cell EPSPs underwent a long-term (>20 min) re duction in peak amplitude (-24%) in cells (n = 12) from animals given unpaired stimulus presentations but to a far less extent (-9%) in cell s (n = 20) from animals given in vivo paired training. Whereas 92% of cells from unpaired animals showed pairing-specific depression, 50% of cells from paired animals showed no depression and in several cases s howed potentiation. Our data establish that there are localized learni ng-specific changes in membrane and synaptic excitability of Purkinje cells in rabbit lobule HVI that can be detected in slices 24 h after c lassical conditioning. Long-term changes within Purkinje cells that ef fect this enhanced excitability may occlude pairing-specific long-term depression.