J Neurophysiol 98: 3809-3812, 2007.
First published October 31, 2007; doi:10.1152/jn.01056.2007
0022-3077/07 $8.00
REPORT
Rapid Consolidation of Motor Memory in the Vestibuloocular Reflex
Heather K. Titley2,
Raquel Heskin-Sweezie2,
Ji-Yeon J. Chung2,
Charles D. Kassardjian1,
Fathima Razik1 and
Dianne M. Broussard1,2,3
1Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto; and 2Department of Physiology and 3Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Submitted 24 September 2007;
accepted in final form 27 October 2007
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ABSTRACT
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Motor memory is relatively labile immediately after learning but can become more stable through consolidation. We investigated consolidation of motor memory in the vestibuloocular reflex (VOR). Cats viewed the world through telescopic lenses during 60 min of passive rotation. Learned decreases (gain-down learning) and increases in the VOR gain (gain-up learning) were measured during sinusoidal rotation at 2 Hz. We found that if rotation in darkness immediately followed learning, the gain of the VOR reverted toward its prelearning value, indicating that expression of the memory was disrupted. If after gain-down learning the cat spent another 60 min stationary without form vision, subsequent disruption did not occur, suggesting that memory had consolidated. Consolidation was less robust for gain-up learning. We conclude that memory in the VOR is initially labile but consolidates rapidly and consistently after gain-down learning.
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INTRODUCTION
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In many neural systems, a newly learned skill or memory is fragile and easily disrupted. Over time, some motor memories can become more resistant to disruption (Brashers-Krug et al. 1996
; Scavio et al. 1992) in a process that is known as consolidation. The vestibuloocular reflex (VOR) is a simple model system for motor learning (for recent reviews, see Boyden et al. 2004; Broussard and Kassardjian 2004). The VOR stabilizes gaze during head movements using signals from the semicircular canals and operates rapidly without time for visual feedback. This means that its response must be precisely calibrated by a learning process. Learning in the VOR is guided primarily by visual error signals. When vision is magnified or miniaturized using telescopic lenses, learning brings about reversible changes in the ratio of eye velocity to head velocity (its "gain") (Miles and Eighmy 1980). We recently reported that memory for decreases in VOR gain was fully consolidated in cats that had worn miniaturizing lenses for 3 days (Kassardjian et al. 2005). In the present study, we describe consolidation over a period of 1–2 h. Because there is abundant evidence that learning of increases ("gain-up" learning) and decreases ("gain-down") rely on different mechanisms (Boyden and Raymond 2003; Li et al. 1995; Miles and Eighmy 1980), they are considered separately.
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METHODS
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Five male cats, 11–24 mo old, were conditioned to accept restraint in a loose drawstring bag and cat chair, then had a head holder and eye coil implanted as previously described (Broussard et al. 1999). Guidelines of the Canadian Council of Animal Care were followed throughout. The cats were restrained sitting upright, with the head rigidly fixed, during turntable-controlled rotation around a vertical axis. We measured eye movements using a phase detector (CNC Engineering) with 17-in field coils. Eye coils were calibrated as previously described (Broussard et al. 1999). The VOR gain was measured during sinusoidal rotation in complete darkness at 2 Hz, with a peak velocity of 10°/s. Turntable ("head") velocity and vertical and horizontal eye position signals were sampled at 4 kHz using Labview software (National Instruments). All signals were digitally low-pass filtered with a rolloff at 55 Hz. Horizontal and vertical eye velocities were calculated using a five-point differentiation algorithm.
Learned decreases and increases in the VOR gain were induced by having the cat wear x0.25 (miniaturizing) or x2 (magnifying) telescopes (Designs for Vision) set in opaque frames that were fitted closely to the cat's head and fixed to the head holder. The learning period encompassed 60 min of rotation with two alternating sum-of-sines (SOS) waveforms each consisting of three 10°/s components at either 0.5, 2, and 10 Hz or 0.2, 1, and 5 Hz. During learning, the cat viewed the lab through the telescopes and the open door of the recording room.
Results from two experimental protocols are reported. In the first protocol, the cat was subjected to 60 min of SOS rotation wearing telescopes ("learning period"), followed by 60 min in complete darkness with the same rotational stimulus ("disruption period"). In the second protocol, a neutral period was inserted between learning and disruption. During the neutral period, the cat was stationary either in the light with the lenses covered by filter paper or in complete darkness. Lenses were worn during the disruption period, and the cat was kept awake during the learning and disruption periods. The disruption stimulus was also presented alone in three cats. At the end of each gain-down training session, the cat was rotated in the light for 30 min without the lenses. For the gain-up experiments, we did not rotate without lenses but waited 
7 days between sessions. The two protocols were repeated alternately one to four times in each cat. In cats Q–S, a third protocol in which the neutral period was 30 min was interspersed with the other two protocols. Results from the third protocol were inconclusive and have been omitted from this report.
To calculate VOR gain, 12 cycles of rotation were averaged, rejecting any cycles that contained saccades. Mean eye velocity was plotted against head velocity (see Fig. 1). Slopes of the lines of best fit to the leftward and rightward half-cycles of rotation were averaged together to obtain the VOR gain. Gain was normalized by dividing each value by the mean prelearning value for each cat. During the learning period, we required a change of 12% of the initial gain, which occurred in the 40 training sessions reported here; if this did not occur, the session was stopped (n = 9). To measure disruption, the five gain measurements encompassing the disruption period were used to generate a regression line for each training session. The normalized, pooled VOR gain values were also analyzed using a one-way ANOVA across the time points in the disruption period. P values were determined using a two-tailed paired Student's t-test.
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FIG. 1. Rotation in darkness disrupted learned changes in vestibuloocular reflex (VOR) gain. Top: sample traces of head and eye velocity, plotted against time during 2-Hz rotation. A learning period of 60 min of rotation with X0.25 telescopes (gain-down) decreased the gain of the VOR (···) from its prelearning value (—). Rotation with X2 telescopes increased the VOR gain (gain-up). Bottom: Eye velocity plotted against head velocity during the VOR before (prelearning) and after learning (post-learning), and after disruption. All traces are averages of 12 cycles of rotation. Data from cats L and S.
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RESULTS
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Figure 1 (top) shows examples of VOR responses to 2-Hz rotation before and after learning. Reliable gain increases or decreases occurred during 1 h of SOS rotation. Figure 1 also shows sample plots of eye versus head velocity in a sequence that illustrates learning followed by disruption for both gain increases and decreases. If learning was immediately followed by SOS rotation in darkness, the VOR gain reverted toward its initial value.
Figure 2 summarizes the time course of the changes in normalized VOR gain. When rotation immediately followed learning (Fig. 2A), an ANOVA showed a significant trend in VOR gain toward its initial value during the disruption period (P < 0.05). The change in VOR gain induced by 60 min of disruption was highly significant both for gain-up and gain-down learning (t-test, P < 0.0001). The phase angle between head and eye velocity averaged 0° and did not change during learning or disruption. Also the disruption stimulus without prior learning did not cause a change in VOR gain (Fig. 2A, 
). The prelearning value of VOR gain was not affected by repeated training sessions nor did the amount of learning show any consistent effects of repeated sessions. Disruption occurred consistently in repeated training sessions without a neutral period, which were interspersed with those containing a neutral period.
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FIG. 2. The normalized gain of the VOR, pooled across subjects and training sessions, as a function of time. A: immediately after learning (—), the learned change could be disrupted by rotation in darkness (···) both for gain-down and gain-up learning.  , gain-down learning; data from cats L, Q, R, and S (n = 15).  , gain-up learning, data from cats S and T (n = 3). , disruption period without learning did not affect the gain of the VOR; data from cats Q, R, and S (n = 12). B: symbols as in A. For gain-down learning, a 60-min neutral period with lenses covered (- - -) prevented disruption; data from L, Q, R, and S (n = 14). A neutral period in complete darkness also prevented disruption (data from S and T, n = 4). For gain-up learning, disruption was not completely prevented; data from S and T (n = 4). Error bars are SD.
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We hypothesized that new memory would consolidate completely if learning was stopped during a neutral period. This prediction was upheld for gain decreases but was not upheld consistently for gain increases. As Fig. 2B illustrates, after a 60-min neutral period the learned decrease in VOR gain was completely resistant to 60 min of disruption. In most cases, the lights were on during the neutral period, but the lenses were covered with paper. In four additional training sessions in two subjects, the cat was in complete darkness during the neutral period; this did not change the result (Fig. 2B, - - -). Learned increases in VOR gain appeared to be more resistant to disruption after a neutral period; some reversal occurred, but the trend toward normal was not significant (2-way ANOVA, P = 0.40).
The results are summarized in Fig. 3. To quantify the effect of the neutral period on disruption, we calculated the slope of the best-fit line representing gain as a function of time during the disruption period. Figure 3A shows the outcome of this analysis for gain-down learning, pooled across subjects. The difference between the regression slopes with and without the neutral period was highly significant for gain-down learning (t-test, P < 0.0001). Figure 3B shows the regression slopes of reversal for each of four subjects. In all cases, a 60-min neutral period prevented disruption. Figure 3C shows the pooled results from two subjects for gain-up learning and disruption, and Fig. 3D summarizes the results from each subject. Disruption was not always completely prevented after gain-up learning. Nevertheless, the effect of the neutral period on the slope of disruption was significant (P < 0.05). In Fig. 3, all neutral periods were in the light without form vision.
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FIG. 3. Slopes of the lines of best fit to gain vs. time during disruption. A: pooled data for gain-down learning. Disruption averaged near 0 after the neutral period. B: individual subjects for gain-down. C: pooled data for gain-up learning. The effect of the neutral period was less robust after gain-up. D: individual subjects for gain-up. Sample sizes are shown above each bar; error bars are SD for the pooled data. ***P < 0.0001, *P < 0.05 (t-test).
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DISCUSSION
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This study describes rapid consolidation of VOR motor memory for gain decreases requiring 1–2 h, similar to the time course for consolidation of the conditioned nictitating-membrane response (NMR) (Cooke et al. 2004). Within this limited time, learned increases in VOR gain showed consolidation that was less robust. We reported earlier that gain-down memory was fully consolidated if learning had continued for 72 h (Kassardjian et al. 2005). In another study, remembered gain decreases did not appear to consolidate fully over 24 h of learning (Cohen et al. 2004). In both of the earlier studies, lenses were worn and movement was permitted until testing for consolidation began with no "neutral" period during which learning was stopped. Therefore newly formed memory could have been present even after 24 h. In the 72-h case, changes in gain appeared to reach an asymptote well before consolidation was tested (Kassardjian et al. 2005) suggesting that no new memory was present at the time of testing. All of these results are consistent with consolidation of new motor memory that requires 1–2 h after learning has stopped.
We did not observe any significant decay of new memory during the neutral period, in agreement with earlier observations that memory does not decay spontaneously (Cohen et al. 2004; Nagao and Kitazawa 2003). There is one report of spontaneous decay (Kuki et al. 2004). In that study, the VOR gain was tested every 10–15 min using rotation at 0.5 Hz, which could have disrupted the learned change; it is also possible that memory for 0.5-Hz rotation is more labile than memory for 2-Hz rotation. Although the mechanism for disruption is not known, climbing fibers in the cerebellar flocculus are known to respond during rotation in darkness (Simpson et al. 2002).
Our observations suggest that within 1 h after a gain decrease is learned, the existing memory consolidates and can no longer be disrupted by rotation in darkness. However, gain increases did not completely consolidate. This could be explained if gain increases are simply more labile (Kuki et al. 2004; Miles and Eighmy 1980). A difference in the speed of consolidation of gain decreases and increases may also be a contributing factor.
Gain-up and -down learning both are thought to involve cerebellar cortical plasticity, although two fundamentally different mechanisms are probably involved (Boyden and Raymond 2003; Li et al. 1995). Over a few days, VOR motor memory appears to shift from cerebellar cortical sites to a more distributed representation (Kassardjian et al. 2005; Shutoh et al. 2006). It is not known whether the rapid consolidation of VOR gain decreases that we describe here requires a change in the memory location. Rapid consolidation of motor memory for conditioned NMRs is thought to take place within the cerebellar cortex (Attwell et al. 2002), and this could also be the case for the VOR. Overall, it is likely that multiple mechanisms contribute to the consolidation of VOR motor memory for gain changes in different directions and over different time scales.
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FOOTNOTES
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Address for reprint requests and other correspondence: D. M. Broussard, MP12-318, Toronto Western Hospital, 399 Bathurst St., Toronto, Ontario M5T 2S8, Canada (E-mail: dianne{at}uhnres.utoronto.ca)
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Copyright © 2007 by the The American Physiological Society.
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ABSTRACT
INTRODUCTION