Cerebellar Inhibitory Output Shapes the Temporal Dynamics of Its Somatosensory Inferior Olivary Input
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The cerebellum is necessary and sufficient for the acquisition and execution of adaptively timed conditioned motor responses following repeated paired presentations of a conditioned stimulus and an unconditioned stimulus. The underlying plasticity depends on the convergence of conditioned and unconditioned stimuli signals relayed to the cerebellum by the pontine nucleus and the inferior olive (IO), respectively. Adaptive timing of conditioned responses relies on the correctly predicted onset of the unconditioned stimulus, usually a noxious somatosensory stimulus. We addressed two questions: First, does the IO relay information regarding the duration of somatosensory stimuli to the cerebellum? Multiple-unit recordings from the IO of anesthetized rats that received periorbital airpuffs of various durations revealed that sustained somatosensory stimuli are invariably transformed into phasic IO outputs. The phasic response was followed by a post-peak depression in IO activity as compared to baseline, providing the cerebellum with a highly synchronous signal, time-locked to the stimulus’ onset. Second, we sought to examine the involvement of olivocerebellar interactions in this signal transformation. Cerebello-olivary inhibition was interrupted using temporary pharmacological inactivation of cerebellar output nuclei, resulting in more sustained (i.e., less synchronous) IO responses to sustained somatosensory stimuli, in which the post-peak depression was substituted with elevated activity as compared to baseline. We discuss the possible roles of olivocerebellar negative-feedback loops and baseline cerebello-olivary inhibition levels in shaping the temporal dynamics of the IO’s response to somatosensory stimuli and the consequences of this shaping for cerebellar plasticity and its ability to adapt to varying contexts.
KeywordsInferior olive Cerebellar nuclei Negative feedback Electrotonic coupling Classical conditioning
We would like to thank Aryeh Taub, Ari Magal, and Dor Konforty for valuable discussions during the preparation of this manuscript. The research leading to these results has received funding from the European Community’s Seventh Framework Program (FP7) under grant agreement #216809, the Converging Technologies (ISF) research grant #1709/07, and ISF grant #390/12 to M.M.; R.H. was also funded by the Dan David Prize Scholarship and the Michael Myslobodsky Foundation.
Conflict of Interest
The authors declare that there is no conflict of interest, financial or otherwise, that might bias this work.
- 38.Witter L, Canto CB, Hoogland TM, De Gruijl JR, De Zeeuw CI. Strength and timing of motor responses mediated by rebound firing in the cerebellar nuclei after Purkinje cell activation. Front Neural Circ. 2013;7:133.Google Scholar
- 42.Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th ed. New York: Academic Press; 1998.Google Scholar
- 49.Welsh JP, Schwartz C. Multielectrode recording from the cerebellum. In: Nicolelis MAL, editor. Methods for neural ensemble recordings. Boca Raton: CRC; 1999. p. 79–100.Google Scholar
- 57.Meng ID, Hu JW, Benetti AP, Bereiter DA. Encoding of corneal input in two distinct regions of the spinal trigeminal nucleus in the rat: cutaneous receptive field properties, responses to thermal and chemical stimulation, modulation by diffuse noxious inhibitory controls, and projections to the parabrachial area. J Neurophysiol. 1997;77(1):43–56.PubMedGoogle Scholar