Plasticity within non-cerebellar pathways rapidly shapes motor performance in vivo

Abstract

Although cerebellar mechanisms are vital to maintain accuracy during complex movements and to calibrate simple reflexes, recent in vitro studies have called into question the widely held view that synaptic changes within cerebellar pathways exclusively guide alterations in motor performance. Here we investigate the vestibulo-ocular reflex (VOR) circuitry by applying temporally precise activation of vestibular afferents in awake-behaving monkeys to link plasticity at different neural sites with changes in motor performance. Behaviourally relevant activation patterns produce rapid attenuation of direct pathway VOR neurons, but not their nerve input. Changes in the strength of this pathway are sufficient to induce a lasting decrease in the evoked VOR. In addition, indirect brainstem pathways display complementary nearly instantaneous changes, contributing to compensating for the reduced sensitivity of primary VOR neurons. Taken together, our data provide evidence that multiple sites of plasticity within VOR pathways can rapidly shape motor performance in vivo.

Plasticity within excitatory and inhibitory pathways of the vestibulo-spinal circuitry guides changes in motor performance

“…Strikingly, the time course of both effects mirror those observed in a recent study of the direct VOR pathway in which plasticity was induced using comparable patterns of vestibular nerve activation 44 . Specifically, in awake, behaving monkeys, first-order central vestibular neurons in both vestibulo-spinal and VOR pathways decreased by ~50% following activation of the vestibular nerve.…”

“…1B) while monkeys were head-fixed in complete darkness, as previously described 44 . Briefly, we first recorded the activity of neurons during a series of test pulse trains (25, 50, 75, 100, 175, 200, 300pps) each lasting 1 s to quantify baseline sensitivities to electrical stimulation of the vestibular nerve.…”

“…The precise time course of neuronal responses to vestibular nerve activation was calculated using a method previously described 44, 91 . Briefly, we measured the latency of the first spike following each individual pulse in a train delivered at 25pps.…”

Vestibular implants studied in animal models: clinical and scientific implications

“…While we could attempt to extrapolate in a qualitative manner from behavior to neuronal responses, the absence of neural recordings has been an important constraint on the work performed by our laboratory and by other laboratories in this field. Neural recordings of vestibular afferents and central vestibular neurons during electrical stimulation provided by a VI, which help clarify the neuronal mechanisms underlying behavioral observations, have only become available recently (Mitchell et al 2016) and will prove crucial to advancing understanding of the brain's response to electrical stimulation provided by a VI.…”

“…Another ongoing problem is to determine how head motion information transduced by an implant can most effectively be encoded to optimize the transmission of information to the brain. Now that recordings in primary vestibular afferents and neurons in the vestibular nuclei are being obtained during prosthetic stimulation (Mitchell et al 2016), the nonphysiological characteristics of the afferent signals generated by the implant can be fully characterized and approaches can be devised to improve the quality of the afferent signal by modifying stimulation techniques. Very high-frequency (5 kHz) background stimulation has been suggested (Rubinstein et al 1999), for example, as a method to desynchronize firing of vestibular afferents within and between fibers that could serve to normalize the pattern of afferent activity produced by the implant.…”