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Featured ArticleArticles, Cellular/Molecular

The Fast and Slow Afterhyperpolarizations Are Differentially Modulated in Hippocampal Neurons by Aging and Learning

Elizabeth A. Matthews, John M. Linardakis and John F. Disterhoft
Journal of Neuroscience 15 April 2009, 29 (15) 4750-4755; https://doi.org/10.1523/JNEUROSCI.0384-09.2009
Elizabeth A. Matthews
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John M. Linardakis
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John F. Disterhoft
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  • Figure 1.
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    Figure 1.

    Performance on trace eyeblink task by young and aged animals. Young and aged animals were included in the learner category if their performance at the eyeblink task by the last training session exceeded 60% conditioned responses (dashed line). Animals that failed to reach criterion were included in the nonlearner group. Groups were intentionally balanced between all behavioral categories with the investigator doing the recording remaining blind to animal training history. The random response rate for pseudoconditioned animals is shown for comparison to the nonlearners. There was no difference in the rate of learning between young and aged animals that learned the task or in the responses of the pseudoconditioned and nonlearners.

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    Figure 2.

    Learning-related changes in the sAHP and fAHP. Learning increases cellular excitability by decreasing the sAHP and the fAHP in both young and aged cells. A , The peak and 1 s measures of the sAHP from young (left) and aged (right) cells is reduced after successfully learning trace eyeblink conditioning (young − peak: learner, −4.36 ± 0.28; nonlearner, −5.71 ± 0.41; pseudo, −5.44 ± 0.34; naive, −5.46 ± 0.27; 1 s, −1.85 ± 0.16; −2.64 ± 0.25, −2.58 ± 0.19, −2.42 ± 0.16) (aged − peak: learner, −4.81 ± 0.37; nonlearner, −6.87 ± 0.30; pseudo, −6.48 ± 0.35; naive, −6.74 ± 0.50; 1 s, −2.00 ± 0.23, −3.23 ± 0.24, −3.21 ± 0.31, −3.27 ± 0.48). B , The absolute fAHP peak voltage is reduced in a train of action potentials in both age groups after learning (first fAHP, young: learner, −52.89 ± 0.69; nonlearner, −57.25 ± 1.17; pseudo, −55.85 ± 1.07; naive, −56.59 ± 1.02) (first fAHP, aged: learner, −52.22 ± 1.04; nonlearner, −56.44 ± 0.79; pseudo, −55.90 ± 0.71; naive, −57.31 ± 1.92). C , Example traces show the sAHP (left), with lines indicating the peak and 1 s measurements and the fAHP (right) for cells from aged animals that learned the trace eyeblink task or were pseudoconditioned. *p < 0.05, **p < 0.01.

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    Figure 3.

    Aging-related changes in the sAHP but not the fAHP. Normal aging increases the sAHP but leaves the fAHP unaffected. A , Because learning-related reductions of the sAHP and fAHP were shown previously for the learner versus control animals, aging-related changes were compared only between the control groups (pseudoconditioned, nonlearner, and naive combined). Both the peak and the 1 s measures of the sAHP were enhanced in aged control cells (peak: young, −5.55 ± 0.20; aged, −6.71 ± 0.21; 1 s: young, −2.56 ± 0.12; aged, −3.24 ± 0.18). B , However, the control groups showed no age-related differences in the absolute fAHP peak voltage for the action potentials in a train (first fAHP: young, −56.30 ± 0.63; aged, −56.75 ± 0.62). Example traces from cells from young and aged naive animals are shown at far right. C , The peak sAHP from both young and aged animals that succeeded in learning the task were not different (learner: young, −4.36 ± 0.28; aged, −4.81 ± 0.37). However, age-related increases in the sAHP were seen in cells from all the control groups. Comparing the fAHP values for the first action potential in a train for each behavioral group reveals that none of the groups showed age-related differences in the fAHP. *p < 0.05; **p < 0.001.

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    Table 1.

    Intrinsic properties of cells by age and learning categories

    n (cells) Rinput (MΩ) Vrest (mV) Vthresh (mV) AP (mV)
    YAYAYAYAYA
    Learner121571.6 ± 6.989.9 ± 6.0−65.3 ± 1.2−65.1 ± 1.4 −46.3 ± 0.8 −41.0 ± 1.4108.2 ± 1.5104.9 ± 2.1
    Nonlearner171978.6 ± 5.986.0 ± 3.8−66.3 ± 0.8−66.1 ± 1.2−46.7 ± 1.0 −42.8 ± 1.2 106.5 ± 1.4106.3 ± 1.7
    Pseudoconditioned151483.4 ± 4.897.7 ± 12.0−66.3 ± 1.2−64.6 ± 1.8−42.1 ± 1.9−38.9 ± 2.2102.8 ± 1.6105.4 ± 2.4
    Naive121187.7 ± 6.5102.5 ± 6.9−65.0 ± 1.2−64.8 ± 1.1−44.0 ± 2.2−44.2 ± 3.9102.5 ± 2.8105.6 ± 3.1
    • Input resistance was calculated from the steady-state membrane voltage during a brief −50 pA step. Resting membrane potential was defined as the membrane potential with no current injection. Action potential threshold was defined as the point at which the first derivative of the membrane potential equaled 20 mV/ms. Action potential height was measured as peak distance from the holding potential. There were significant differences in the threshold between young and aged cells in the learner and nonlearner groups (bold: learner, F (1,30) = 8.378, p < 0.01; nonlearner, F (1,33) = 6.133, p < 0.05). There was a trend toward increased input resistance between young and aged cells in the learner group (learner, F (1,30) = 3.343, p = 0.08).

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The Journal of Neuroscience: 29 (15)
Journal of Neuroscience
Vol. 29, Issue 15
15 Apr 2009
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The Fast and Slow Afterhyperpolarizations Are Differentially Modulated in Hippocampal Neurons by Aging and Learning
Elizabeth A. Matthews, John M. Linardakis, John F. Disterhoft
Journal of Neuroscience 15 April 2009, 29 (15) 4750-4755; DOI: 10.1523/JNEUROSCI.0384-09.2009

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The Fast and Slow Afterhyperpolarizations Are Differentially Modulated in Hippocampal Neurons by Aging and Learning
Elizabeth A. Matthews, John M. Linardakis, John F. Disterhoft
Journal of Neuroscience 15 April 2009, 29 (15) 4750-4755; DOI: 10.1523/JNEUROSCI.0384-09.2009
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