Relating Cerebellar Purkinje Cell Activity to the Timing and Amplitude of Conditioned Eyelid Responses

Abstract

How Purkinje cell (PC) activity may be altered by learning is central to theories of the cerebellum. Pavlovian eyelid conditioning, because of how directly it engages the cerebellum, has helped reveal many aspects of cerebellar learning and the underlying mechanisms. Theories of cerebellar learning assert that climbing fiber inputs control plasticity at synapses onto PCs, and thus PCs control the expression of learned responses. We tested this assertion by recording 184 eyelid PCs and 240 non-eyelid PCs during the expression of conditioned eyelid responses (CRs) in well trained rabbits. By contrasting the responses of eyelid and non-eyelid PCs and by contrasting the responses of eyelid PCs under conditions that produce differently timed CRs, we test the hypothesis that learning-related changes in eyelid PCs contribute to the learning and adaptive timing of the CRs. We used a variety of analyses to test the quantitative relationships between eyelid PC responses and the kinematic properties of the eyelid CRs. We find that the timing of eyelid PC responses varies systematically with the timing of the behavioral CRs and that there are differences in the magnitude of eyelid PC responses between larger-CR, smaller-CR, and non-CR trials. However, eyelid PC activity does not encode any single kinematic property of the behavioral CRs at a fixed time lag, nor does it linearly encode CR amplitude. Even so, the results are consistent with the hypothesis that learning-dependent changes in PC activity contribute to the adaptively timed expression of conditioned eyelid responses.

Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

“…The present results show that individual Purkinje cells can also acquire pause responses to two CSs of different modalities. This is consistent with a recent study in which it was shown that Purkinje cells can acquire pause responses to two tones with different frequencies (36). Next, we examined the effect of presenting two CSs simultaneously, as a compound CS.…”

Taxonomies of timing: where does the cerebellum fit in?

“…As summarized in this brief review, the evidence indicates that the domain encompasses both motor and perceptual timing, and is observed in both explicit and implicit tasks. We have highlighted one important constraint, namely that the cerebellum may be required when tasks require timing single intervals, or what we have called event timing [38, 39], but not when timing is inherent to rhythmic or continuous dynamics.…”

“…Indeed, in trained animals, lesions of the cerebellar cortex abolish the precise timing; the CR is now time-locked to the CS rather than the US [35]. Eyeblink conditioning has been perhaps the most sophisticated model system for studying the cellular and molecular mechanisms of timing [37, 38*, 39]. …”

A comparative approach to cerebellar function: insights from electrosensory systems

“…CRs are believed to be due, at least in part, to “learned” pauses in Purkinje cell firing[29]. The timing of such pauses is matched to the CS-US delay and bears a systematic relationship to the eyelid CR[30–33]. Leading models of eyelid conditioning suggest that the pauses emerge as a result of plasticity at parallel fiber synapses[34;35].…”