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Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR.

Schicknick H, Schott BH, Budinger E, Smalla KH, Riedel A, Seidenbecher CI, Scheich H, Gundelfinger ED, Tischmeyer W - Cereb. Cortex (2008)

Bottom Line: This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control.Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls.The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany.

ABSTRACT
Previous studies in the auditory cortex of Mongolian gerbils on discrimination learning of the direction of frequency-modulated tones (FMs) revealed that long-term memory formation involves activation of the dopaminergic system, activity of the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis. This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially improved gerbils' FM discrimination learning when administered systemically or locally into the auditory cortex shortly before, shortly after, or 1 day before conditioning. Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect. By immunohistochemistry, D1 dopamine receptors were identified in the gerbil auditory cortex predominantly in the infragranular layers. Together, these findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours or days the consolidation of memory required for the discrimination of complex auditory stimuli.

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Related in: MedlinePlus

Local injections of SKF-38393 into the gerbil auditory cortex 1 day before differential conditioning to FMs contribute to between-session information processing. Data collected in Experiments 3–5 were pooled for groups that received local injections of either vehicle (n = 35) or SKF-38393 (n = 36) one day before, and no injections or vehicle injections shortly after initial training. Each training session was subdivided into 5 blocks of 12 trials. Discrimination rates D per trial block are shown. All data points represent group means ± SEM; (*) significantly different from the value of vehicle-treated controls; (#) significantly different from the corresponding value in trial block 5 of session 1.
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fig5: Local injections of SKF-38393 into the gerbil auditory cortex 1 day before differential conditioning to FMs contribute to between-session information processing. Data collected in Experiments 3–5 were pooled for groups that received local injections of either vehicle (n = 35) or SKF-38393 (n = 36) one day before, and no injections or vehicle injections shortly after initial training. Each training session was subdivided into 5 blocks of 12 trials. Discrimination rates D per trial block are shown. All data points represent group means ± SEM; (*) significantly different from the value of vehicle-treated controls; (#) significantly different from the corresponding value in trial block 5 of session 1.

Mentions: To assess whether SKF-38393 infused into the auditory cortex 1 day prior to initial conditioning to FMs affects retention and retrieval of memory acquired already during session 1 or only additional learning during session 2, data collected in Experiments 3–5 were pooled and subdivided into 5 blocks of 12 trials per training session, referred to as trial blocks 1–5. Included in the statistical analysis were data derived from gerbils that received either vehicle or SKF-38393–only injections 1 day before, and either vehicle or no injections shortly after initial training. Data were assigned to 1 of 2 groups according to the preconditioning treatments. Figure 5 shows the mean discrimination rates D calculated per group and trial block. An ANOVA comparing D over sessions and trial blocks across treatment groups revealed significant effects of group (F1,69 = 13.60, P < 0.001) and session (F1,69 = 78.69, P < 0.001), a significant group × session interaction (F1,69 = 19.97, P < 0.001), and, importantly, a significant group × session × trial block interaction (F4,276 = 3.20, P = 0.013).


Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR.

Schicknick H, Schott BH, Budinger E, Smalla KH, Riedel A, Seidenbecher CI, Scheich H, Gundelfinger ED, Tischmeyer W - Cereb. Cortex (2008)

Local injections of SKF-38393 into the gerbil auditory cortex 1 day before differential conditioning to FMs contribute to between-session information processing. Data collected in Experiments 3–5 were pooled for groups that received local injections of either vehicle (n = 35) or SKF-38393 (n = 36) one day before, and no injections or vehicle injections shortly after initial training. Each training session was subdivided into 5 blocks of 12 trials. Discrimination rates D per trial block are shown. All data points represent group means ± SEM; (*) significantly different from the value of vehicle-treated controls; (#) significantly different from the corresponding value in trial block 5 of session 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2567422&req=5

fig5: Local injections of SKF-38393 into the gerbil auditory cortex 1 day before differential conditioning to FMs contribute to between-session information processing. Data collected in Experiments 3–5 were pooled for groups that received local injections of either vehicle (n = 35) or SKF-38393 (n = 36) one day before, and no injections or vehicle injections shortly after initial training. Each training session was subdivided into 5 blocks of 12 trials. Discrimination rates D per trial block are shown. All data points represent group means ± SEM; (*) significantly different from the value of vehicle-treated controls; (#) significantly different from the corresponding value in trial block 5 of session 1.
Mentions: To assess whether SKF-38393 infused into the auditory cortex 1 day prior to initial conditioning to FMs affects retention and retrieval of memory acquired already during session 1 or only additional learning during session 2, data collected in Experiments 3–5 were pooled and subdivided into 5 blocks of 12 trials per training session, referred to as trial blocks 1–5. Included in the statistical analysis were data derived from gerbils that received either vehicle or SKF-38393–only injections 1 day before, and either vehicle or no injections shortly after initial training. Data were assigned to 1 of 2 groups according to the preconditioning treatments. Figure 5 shows the mean discrimination rates D calculated per group and trial block. An ANOVA comparing D over sessions and trial blocks across treatment groups revealed significant effects of group (F1,69 = 13.60, P < 0.001) and session (F1,69 = 78.69, P < 0.001), a significant group × session interaction (F1,69 = 19.97, P < 0.001), and, importantly, a significant group × session × trial block interaction (F4,276 = 3.20, P = 0.013).

Bottom Line: This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control.Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls.The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany.

ABSTRACT
Previous studies in the auditory cortex of Mongolian gerbils on discrimination learning of the direction of frequency-modulated tones (FMs) revealed that long-term memory formation involves activation of the dopaminergic system, activity of the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis. This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially improved gerbils' FM discrimination learning when administered systemically or locally into the auditory cortex shortly before, shortly after, or 1 day before conditioning. Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect. By immunohistochemistry, D1 dopamine receptors were identified in the gerbil auditory cortex predominantly in the infragranular layers. Together, these findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours or days the consolidation of memory required for the discrimination of complex auditory stimuli.

Show MeSH
Related in: MedlinePlus