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Behavioral/Systems/Cognitive

Time-Dependent Reorganization of the Brain Components Underlying Memory Retention in Trace Eyeblink Conditioning

Kaori Takehara, Shigenori Kawahara and Yutaka Kirino
Journal of Neuroscience 29 October 2003, 23 (30) 9897-9905; DOI: https://doi.org/10.1523/JNEUROSCI.23-30-09897.2003
Kaori Takehara
1Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, and 2Core Research for Evolution Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan
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Shigenori Kawahara
1Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, and 2Core Research for Evolution Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan
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Yutaka Kirino
1Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, and 2Core Research for Evolution Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan
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    Figure 1.

    Representative photomicrographs of coronal brain sections stained with cresyl violet and extent of the lesion reconstructed from brain sections. A, The cortical lesion group. B, The hippocampal lesion group. C, The medial prefrontal cortical lesion group. D, The cerebellar lesion group. Scale bars, 2 mm. The black and striped areas indicate the smallest and largest lesions, respectively. Numbers to the left indicate stereotaxic coordinates relative to bregma (Paxinos and Watson, 1986).

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    Figure 2.

    Effect of a hippocampal lesion on memory retention. A, Mean percentage of adaptive CRs in the 1 d group. The abscissa shows the session number after the lesion was made; the session at which the rat reached the criterion is denoted –1. Negative and positive values indicate the pre-lesion and post-lesion sessions. spont., Spontaneous eyeblink frequency. The hippocampal lesion group (•, 1d hipp; n = 7) showed a significantly lower adaptive CR% through the post-lesion sessions compared with the cortical lesion group (○, 1d cort; n = 7). B, Mean percentage of adaptive CRs in the 1 week group. The hippocampal lesion group (•, 1w hipp; n = 7) tended to exhibit a lower adaptive CR% than the cortical lesion group (○, 1w cort; n = 7) through the post-lesion sessions, although this difference was not statistically significant. C, Mean percentage of adaptive CRs in the 2 weeks group. The hippocampal lesion group (•, 2w hipp; n = 7) exhibited a slightly lower adaptive CR% than the cortical lesion group (○, 2w cort; n = 7) throughout the post-lesion sessions, although this difference was not statistically significant. D, Mean percentage of adaptive CRs in the 4 weeks group. The hippocampal lesion group (•, 4w hipp; n = 7) exhibited as robust an adaptive CR as the cortical lesion group (○, 4w cort; n = 7) through the post-lesion sessions. E, Mean percentage of adaptive CRs in the 1 d group (post-10). The hippocampal lesion group [•, 1d hipp (post-10); n = 6] did not recover to the level of the control group [○, 1d cort (post-10); n = 6] during 10 d of the post-lesion sessions. All data points represent group mean ± SEM.

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    Figure 3.

    Effect of a mPFC lesion on memory retention. A, Mean percentage of adaptive CRs in the 1 d group. The abscissa shows the session number after the lesion was made; the session at which the rat reached the criterion is denoted –1. Negative and positive values indicate the pre-lesion and post-lesion sessions. spont., Spontaneous eyeblink frequency. The mPFC lesion group (•, 1d mPFC; n = 7) exhibited a slightly lower adaptive CR% than the sham operation group (○, 1d sham; n = 7) through the post-lesion sessions. B, Mean percentage of adaptive CRs in the 2 weeks group. The mPFC lesion group (•, 2w mPFC; n = 6) was mildly impaired in its adaptive CR% compared with the sham operation group (○, 2w sham; n = 6) through the post-lesion sessions. C, Mean percentage of the adaptive CRs in the 4 weeks group. The mPFC lesion group (•, 4w mPFC; n = 6) exhibited a great impairment in retention of the adaptive CR% compared with its corresponding sham operation group (○, 4w sham; n = 7). All data points represent group mean ± SEM.

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    Figure 4.

    Effect of a cerebellar lesion on memory retention. A, Mean percentage of adaptive CRs in the 1 d group. The abscissa shows the session number after the lesion was made; the session at which the rat reached the criterion is denoted –1. Negative and positive values indicate the pre-lesion and post-lesion sessions. spont., Spontaneous eyeblink frequency. The cerebellar lesion group (•, 1d cere; n = 6) showed a significantly lower CR% compared with its sham operation group (○, 1d sham; n = 7) during the post-lesion sessions. B, Mean percentage of adaptive CRs in the 2 weeks group. The cerebellar lesion group (•, 2w cere; n = 6) was greatly impaired in its retention of the adaptive CR% compared with the cerebellar sham operation group (○, 2w sham; n = 6). C, Mean percentage of the adaptive CRs in the 4 weeks group. The cerebellar lesion group (•, 4w cere; n = 6) exhibited significantly fewer adaptive CRs compared with the sham operation group (○, 4w sham; n = 6) through the post-lesion sessions. All data points represent group mean ± SEM.

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    Figure 5.

    Percentage of adaptive CRs in the first post-lesion session as a function of the time interval between learning and the lesion. A, Mean percentage of the adaptive CRs of the hippocampal lesion group (•, hipp) and the cortical lesion group (○, cort). The abscissa indicates the interval between the last acquisition session and the second surgery (lesion). The hippocampal lesion produced temporally graded retrograde amnesia. B, Mean percentage of the adaptive CRs of the mPFC lesion group (•, mPFC) and its corresponding sham operation group (○, sham). Ablation of the mPFC produced retrograde amnesia with temporal characteristics that were the reverse of those produced by a hippocampal lesion. C, Mean percentage of the adaptive CRs of the cerebellar lesion group (•, cere) and the sham operation group (○, sham). A cerebellar lesion produced retrograde amnesia without a temporal gradient. All data points represent group mean ± SEM.

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    Figure 6.

    The temporal pattern of the CR of the last pre-lesion session (pre –1), the first post-lesion session (post 1), and the third post-lesion session (post 3). A, Averaged EMG amplitude of the cortical lesion group (thin line, cort) and hippocampal lesion group (thick line, hipp). There was no obvious difference of the temporal pattern of CRs between groups, except the third post-lesion session of the 1 d hippocampal lesion group. B, Averaged EMG amplitude of the sham operation group (thin line, sham) and the mPFC lesion group (thick line, mPFC). There was no obvious difference of the temporal pattern of CRs between groups. C, Averaged EMG amplitude of the sham operation group (thin line, sham) and the cerebellar lesion group (thick line, cere). There was no obvious difference of the temporal pattern of CRs between groups, except the third post-lesion session of the 4 weeks cerebellar lesion group. The solid line under each trace indicates the timing of the 350 msec CS. The vertical scale indicates the average EMG amplitude before the CS presentation; the horizontal scale indicates 100 msec.

Tables

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    Table 1.

    Summary of CR peak latency in the first post-lesion session

    Group 1 d (msec) 1 week (msec) 2 weeks (msec) 4 weeks (msec)
    Cortical lesion 516 ± 23.2 514 ± 16.9 575 ± 26.3 546 ± 34.8
    Hippocampal lesion 500 ± 28.9 546 ± 27.1 582 ± 46.0 569 ± 18.6
    Sham operation (mPFC) 574 ± 30.4 566 ± 35.1 581 ± 13.1
    mPFC lesion 616 ± 32.8 582 ± 24.7 608 ± 23.2
    Sham operation (cerebellum) 571 ± 23.1 625 ± 36.3 583 ± 29.9
    Cerebellar lesion 574 ± 30.9 621 ± 12.0 547 ± 29.9
    • No lesion group differed from its corresponding control group in CR peak latency. All data points represent group mean ± SEM.

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    Table 2.

    Summary of CR peak latency in the third post-lesion session

    Group 1 d (msec) 1 week (msec) 2 weeks (msec) 4 weeks (msec)
    Cortical lesion 563 ± 20.2 497 ± 18.2 578 ± 30.5 555 ± 27.3
    Hippocampal lesion 468 ± 24.4* 598 ± 42.9 591 ± 21.0 577 ± 27.4
    Sham operation (mPFC) 617 ± 13.1 591 ± 24.9 586 ± 9.20
    mPFC lesion 629 ± 12.6 592 ± 36.0 620 ± 26.4
    Sham operation (cerebellum) 619 ± 19.8 644 ± 27.9 644 ± 23.6
    Cerebellar lesion 581 ± 29.7 627 ± 51.3 555 ± 27.6*
    • Most groups did not differ from their corresponding control groups in CR peak latency except the 1 d hippocampal and the 4 weeks cerebellar lesion group. All data points represent group mean ± SEM. *p<0.05.

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The Journal of Neuroscience: 23 (30)
Journal of Neuroscience
Vol. 23, Issue 30
29 Oct 2003
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Time-Dependent Reorganization of the Brain Components Underlying Memory Retention in Trace Eyeblink Conditioning
Kaori Takehara, Shigenori Kawahara, Yutaka Kirino
Journal of Neuroscience 29 October 2003, 23 (30) 9897-9905; DOI: 10.1523/JNEUROSCI.23-30-09897.2003

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Time-Dependent Reorganization of the Brain Components Underlying Memory Retention in Trace Eyeblink Conditioning
Kaori Takehara, Shigenori Kawahara, Yutaka Kirino
Journal of Neuroscience 29 October 2003, 23 (30) 9897-9905; DOI: 10.1523/JNEUROSCI.23-30-09897.2003
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Keywords

  • memory consolidation
  • classical conditioning
  • eyeblink
  • hippocampus
  • prefrontal cortex
  • cerebellum

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