PT  - JOURNAL ARTICLE
AU  - Daniel Z. Wetmore
AU  - Dan-Anders Jirenhed
AU  - Anders Rasmussen
AU  - Fredrik Johansson
AU  - Mark J. Schnitzer
AU  - Germund Hesslow
TI  - Bidirectional Plasticity of Purkinje Cells Matches Temporal Features of Learning
AID  - 10.1523/JNEUROSCI.2883-13.2014
DP  - 2014 Jan 29
TA  - The Journal of Neuroscience
PG  - 1731--1737
VI  - 34
IP  - 5
4099  - http://www.jneurosci.org/content/34/5/1731.short
4100  - http://www.jneurosci.org/content/34/5/1731.full
SO  - J. Neurosci.2014 Jan 29; 34
AB  - 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.