Plasticity in the Vestibulo-Ocular Reflex: A New Hypothesis

Abstract

The vestibulo-ocular reflex functions to prevent head movements from disturbing retinal images by generating compensatory eye movements to offset the head movements. In the monkey--the species mainly under consideration here--this reflex is machine-like and very effective. In the short-term, the VOR operates as an open-loop control system without the benefit of feedback and its performance is fixed and immutable: No matter what pattern of eye-head coordination the animal uses to view external objects, there is a continuing need for the VOR and it continues to operate; however, should the VOR consistently fail to stabilize the retinal images during head turns, it will gradually undergo long-term adaptive gain changes that restore, that stability. This adaptive capability is ultimately dependent upon vision, and a variety of optical devices that disturb the visual input normally associated with lead turns have been used to induce large changes in the reflex. Insofar as the monkey is concerned, all of the available evidence suggests to us that the modifiable elements underlying these long-term adjustments are located in the brainstem vestibular pathways and not, as previously suggested by others, in the floccular lobes of the cerebellum. However, the flocculus does appear to have an important, inductive role in the adaptive process providing at least part of the error signal guiding the long-term adjustments in the brainstem. In our view, the VOR is a particularly well-defined example of a plastic system and promises to be a most useful model for studying the cellular mechanisms underlying memory and learning the central nervous system.

A Mechanism for Savings in the Cerebellum

“…The reversibility of plasticity at gr3Pk j synapses is at present an assumption of the simulation because the evidence to date suggests that LTP-LTD at this synapse are not mutually reversible because the expression of the former seems to be presynaptic (Salin et al, 1996), whereas that of the later is clearly postsynaptic (Linden, 1994). As first suggested by Miles and Lisberger (1981) and supported more recently by theoretical (Medina and and empirical (Perrett and Mauk, 1995;Aizenman and Linden, 2000) analyses, plasticity in the cerebellar nucleus was controlled by Purkinje cell inputs. Thus, the excitatory mf3nuc synapses underwent LTD when active during strong inhibitory input from the Purkinje cells and LTP when active during a transient pause in this inhibition.…”

“…Based on empirical evidence, plasticity in the cerebellar cortex was controlled by climbing fiber inputs such that gr3Pkj synapses active during a climbing fiber input decreased in strength (LTD) and those active in the absence of a climbing fiber input increased in strength (LTP) (Sakurai, 1987;Ito, 1989;Hirano, 1990;Shibuki and Okada, 1992;Linden, 1994;Salin et al, 1996). As first suggested by Miles and Lisberger (1981) and supported more recently by theoretical and empirical (Perrett and Mauk, 1995;Aizenman and Linden, 2000) analyses, plasticity in the cerebellar nucleus was controlled by inhibitory inputs from Purkinje cells. Thus, LTD of mf3nuc synapses occurred during strong inhibitory Purkinje cell inputs, whereas LTP was induced during transient pauses in this inhibition.…”

Learning-Induced Plasticity in Deep Cerebellar Nucleus

“…The existence of an analogous form of plasticity in the vestibular nucleus and the notion that its induction is controlled by inputs from Purkinje cells was first suggested by Miles and Lisberger (1981) for another form of cerebellar motor learning known as vestibulo-ocular reflex (VOR) adaptation, and evidence in support of this view has been obtained in subsequent studies (Lisberger, 1994;du Lac et al, 1995). The present findings underscore the similarities between eyelid conditioning and adaptation of the VOR, in that they are both forms of cerebellar motor learning that induce plasticity at two sites, one in the cerebellar cortex and another in their target neurons in the deep cerebellar/vestibular nuclei.…”

“…In principle, the plasticity could be driven by the activity in any of the inputs to the AIN or by activity in the AIN itself (Medina and Mauk, 1999). Miles and Lisberger (1981) first proposed that Purkinje cells could control the induction of synaptic changes in the deep cerebellar/vestibular nuclei, and subsequent computational studies were in agreement (Medina and Mauk, 1999). Recent studies have shown that rebound excitation of AIN neurons following burst-pause modulation of Purkinje cell activity is sufficient to increase both the intrinsic excitability of AIN neurons (Zhang et al, 2004) and the strength of mossy fiber synapses (Pugh and Raman, 2006).…”

“…This suggests that initial acquisition of eyelid responses is slow, because it requires establishing plasticity at two sites, whereas relearning after extinction is faster, because plasticity is already induced in the AIN. Interestingly, a more natural form of cerebellar learning such as VOR adaptation does not display robust savings (Miles and Lisberger, 1981), perhaps because mossy fiber synapses onto the vestibular nuclei already exist. Nonetheless, recent studies of VOR adaptation showing that the effects of reversible cerebellar cortex lesions depend on the amount of training are generally consistent with these findings, further underscoring the parallels between eyelid conditioning and VOR adaptation (Kassardjian et al, 2005;Shutoh et al, 2006).…”