Role of granule-cell transmission in memory trace of cerebellum-dependent optokinetic motor learning.
Adaptation of the optokinetic response (OKR) is an eye movement enhanced by repeated motion of a surrounding visual field and represents a prototype of cerebellum-dependent motor learning. Purkinje cells and vestibular nuclei (VN) receive optokinetic and retinal slip signals via the mossy fiber-granule cell pathway and climbing-fiber projections, respectively. To explore the neural circuits and mechanisms responsible for OKR adaptation, we adopted the reversible neurotransmission-blocking (RNB) technique, in which granule-cell transmission to Purkinje cells was selectively and reversibly blocked by doxycycline-dependent expression of transmission-blocking tetanus toxin in granule cells. Blockade of granule-cell inputs abolished both short-term and long-term OKR adaptation induced by repeated OKR training, but normal levels of both responses were immediately evoked in the pretrained RNB mice by OKR retraining once granule-cell transmission had recovered. Importantly, eye movement elicited by electrical stimulation of the cerebellar focculus was elevated by long-term but not by short-term OKR training in adaptive OKR-negative RNB mice. Furthermore, when the flocculus of adaptive OKR-negative RNB mice was electrically excited in-phase with OKR stimulation, these mice exhibited long-term adaptive OKR. These results indicate that convergent information to the VN was critical for acquisition and storage of long-term OKR adaptation with conjunctive action of Purkinje cells for OKR expression. Interestingly, in contrast to conditioned eyeblink memory, the expression of once acquired adaptive long-term OKR was not abrogated by blockade of granule-cell transmission, suggesting that distinct forms of neural plasticity would operate in different forms of cerebellum-dependent motor learning.
Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Norio
N
Wada
Kazuo
K
Funabiki
Shigetada
S
Nakanishi
D000222:Adaptation, Physiological; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D005133:Eye Movements; D007858:Learning; D008568:Memory; D051379:Mice; D009043:Motor Activity; D009473:Neuronal Plasticity
cerebellar circuitry; optokinetic adaptation; reversible neurotransmission blockade