Question #11: Where does the plasticity of the vestibular ocular reflex occur?

One of the main roles of the semicircular canal system is to maintain the location of eye focus despite any head movements. The three pairs eye muscles are matched by the three planes of the semicircular canals, and each plane of the canals have direct control over one of these muscle pairs–either the medial and lateral rectus, or the superior and inferior rectus, or the inferior and superior oblique. This control must occur quickly in order to be effective. Eye movements lag head ones by only 10 milliseconds, and the pathway from semicircular canal to eye muscle contains only three feedforward neurons, making this vestibular-ocular reflex (VOR) one of the fastest in the human body.

Researchers in this field define “gain” as magnitude of the eye movement velocity divided by the magnitude of the head movement velocity during head turns in darkness. In typical primates the gain should be 1.0, but the reflex shows adaptation via motor learning if the image tends to have additional movement in one direction or the other. For example, if head movements lead to image movement in the opposite direction, the reflex will adapt to increase the gain and keep pace with the image. If the image movement is in the same direction as the head movement, the gain will decrease to compensate. So the VOR reflex in primates is, in a sense, a model system for plasticity, and in particular for simple motor learning. The debate over the past quarter century has focused on which of the following hypotheses best explains how this motor learning occurs:

1) The cerebellum stores the memory for the VOR adaptation. In this model, head movements lead to visually-dependent climbing fiber activity and semicircular canal-dependent parallel fiber activity. The climbing fibers report error between eye velocity and target velocity, leading to a change in the postysnaptic activity of Purkinje cell synapses and altering their synaptic weights with the parallel fibers. This change in synapse strength encodes the altered motor memory. Evidence: Lesions to the cerebellar flocculus eliminate VOR adaptation; activity of floccular Purkinje cells is highly correlated to adaptation of the VOR in monkeys (see here); and injecting 10 μM hemoglobin (to absorb N2O, diminishing cerebellar synaptic plasticity) into the subdural space over the flocculus on the same side as the observed eye eliminates VOR adaptation in monkeys. Moreover, when Nagao and Kitazawa (2003) injected the depressant lidocaine into the floculli, their monkey’s immediately reversed the VOR adaptation they had learned during 2 hours of visual–vestibular training.* These results indicate that the flocculus is at least necessary for short term cerebellar memory.

2) The role of cerebellum is to compute signal guiding induction of plasticity, but not to store the motor memory. In this model, Purkinje cells in the cerebellum convey the instructive error signal to the vestibular nucleus of the pons and medulla. So, the synaptic changes necessary for memory encoding occur between the axons aferrent to and neurons in the vestibular nucleus. Evidence: It’s possible that the correlations of floccular Purkinje cells and adaptation of the VOR in monkeys (from above) can be better explained by altered input to the cerebellum from mossy fibers that relays an efference copy of adaptation stored in the vestibular nucleus. To test this, researchers isolate the input from vestibular pathways to cerebellar Purkinje cells, possibly by using VOR cancellation. They find that the pattern of Purkinje cell sensitivity is opposite to that required by the VOR adaptation, meaning that VOR plasticity could not be dependent upon the Purkinje cells. Moreover, lesions to the cerebellum do not completely eliminate the memory of VOR adaptation. Finally, Porill and Dean’s (2007) computer sim that includes a realistic 100 ms delay before a report of the retinal error to the cerebellum prevents cerebellum-based learning above frequencies of 2.5 Hz, even though VOR adaptation can occur at ranges up to 25 Hz. In order to account for the biological VOR adaptation capability, extracerebellelar plasticity must be postulated. This second theory now seems to be the consensus view.

For more recent work on the role of the cerebellum and brainstem in the VOR, see here and here. The general lesson I draw from this research is that models based heavily on anatomy, like the classical Marr-Albus-Ito theory (#1) can look very appealing but must be heavily validated just like any other theory before they can be accepted.

* During the adaptation phase the monkeys in the lidocaine group had an increase in gain from 0.76 +/- 0.05 to 0.95 +/- 0.05, but this gain decreased to 0.76 +/- 0.08 only 10 minutes after injection of lidocaine. As opposed to the control solution in which the adaptation remained steady for ~ 1 hour of darkness.

References

Tabata K, et al. 2002 Computational Study on Monkey VOR Adaptation and Smooth Pursuit Based on the Parallel Control-Pathway Theory. J Neurophysiol. Link.

Nagao S, et al. 2003 Effects of reversible shutdown of the monkey flocculus on the retention of adaptation of the horizontal vestibulo-ocular reflex. Neuroscience doi:10.1016/S0306-4522(02)00991-0 .

Nagao S, et al. 1991 Subdural application of hemoglobin to the cerebellum blocks vestibuloocular reflex adaptation. Neuroreport. PubMed.

Porrill J, et al. 2007 Cerebellar Motor Learning: When Is Cortical Plasticity Not Enough? PLOS Comp Bio. Link.

Boyden ES, et al. 2004 Cerebellum-dependent learning: the role of multiple plasticity mechanisms. Annu. Rev. Neuroscience. doi: 10.1146/annurev.neuro.27.070203.144238

De Schutter E, et al. 1996 The cerebellum: cortical processing and theory. Current Opinion in Neurobio. Link.