Bidirectional plasticity of Purkinje cells matches temporal features of learning.
Many forms of learning require temporally ordered stimuli. In Pavlovian eyeblink conditioning, a conditioned stimulus (CS) must precede the unconditioned stimulus (US) by at least about 100 ms for learning to occur. Conditioned responses are learned and generated by the cerebellum. Recordings from the cerebellar cortex during conditioning have revealed CS-triggered pauses in the firing of Purkinje cells that likely drive the conditioned blinks. The predominant view of the learning mechanism in conditioning is that long-term depression (LTD) at parallel fiber (PF)-Purkinje cell synapses underlies the Purkinje cell pauses. This raises a serious conceptual challenge because LTD is most effectively induced at short CS-US intervals, which do not support acquisition of eyeblinks. To resolve this discrepancy, we recorded Purkinje cells during conditioning with short or long CS-US intervals. Decerebrated ferrets trained with CS-US intervals ≥150 ms reliably developed Purkinje cell pauses, but training with an interval of 50 ms unexpectedly induced increases in CS-evoked spiking. This bidirectional modulation of Purkinje cell activity offers a basis for the requirement of a minimum CS-US interval for conditioning, but we argue that it cannot be fully explained by LTD, even when previous in vitro studies of stimulus-timing-dependent LTD are taken into account.
James H. Clark Center for Biomedical Engineering and Sciences, and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, and Lund University, Department of Experimental Medicine, S 221 84 Lund, Sweden.
Daniel Z
DZ
Wetmore
Dan-Anders
DA
Jirenhed
Anders
A
Rasmussen
Fredrik
F
Johansson
Mark J
MJ
Schnitzer
Germund
G
Hesslow
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002531:Cerebellum / Q000166:cytology; D003215:Conditioning, Eyelid / Q000502:physiology*; D003655:Decerebrate State / Q000503:physiopathology; D004558:Electric Stimulation / Q000009:adverse effects; D004576:Electromyography; D005289:Ferrets; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology
Purkinje cells; cerebellum; conditioning; learning; temporal; timing