SYSTEMIC HARMALINE BLOCKS ASSOCIATIVE AND MOTOR LEARNING BY THE ACTIONS OF THE INFERIOR OLIVE

Is there a role for the inferior olive in learning? Novel paradigms of conditioning involving tongue protrusion were developed using the rat to test whether: (a) the indole alkaloid harmaline blocks associative learning via actions within the inferior olive, and (b) the inferior olive is required for associative and motor learning. Harmaline blocke d associative learning as measured by the absence of conditioned respo nses to a tone over six daily sessions of conditioning and the absence of retention without harmaline. Harmaline's effect on associative lea rning was completely blocked by prior removal of the inferior olive wi th 3-acetylpyridine. Rats whose inferior olives were chronically lesio ned showed normal associative learning, normal associative memory, and could learn to modify tongue protrusion via a motor learning paradigm involving response shaping. Removal of the inferior olive degraded th e performance of the licking motor system by increasing the latency of conditioned tongue protrusions and by increasing the temporal variabi lity of rhythmic licking elicited by intraoral water. The experiments raise doubt as to whether the inferior olive encodes memory in the cer ebellum but demonstrate that the inferior olive is essential for the t emporal precision of movement. The results indicate that harmaline's a ntilearning action is produced by its ability to exaggerate the normal propensity of olivary neurons to fire rhythmically, a process that mu st be constrained under physiological conditions for normal learning t o occur. it is concluded that there may be an important role for the r hythmic activity of inferior olivary neurons in the temporal processes that underlie both motor control and learning.