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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

Preconditioning ip injection of the D1/D5 agonist SKF-38393 into naïve gerbils improves learning, and presession ip injection of the D1/D5 antagonist SCH-23390 into well-trained gerbils impairs performance of the FM discrimination. Data were collected in Experiment 1. (A) Design of pharmacological treatment. Gerbils were randomly assigned to 1 of 2 groups, A and B, and trained on the FM discrimination task once per day for a total of 18 sessions. Training-free intervals of 2 days were interspersed after sessions 5, 10, and 15. Injections of vehicle (Veh), SKF-38393 (SKF; 5 mg/kg), or SCH-23390 (SCH; 0.1 mg/kg) were performed 30 min prior to the indicated training sessions. (B) Discrimination rates D per training session. Arrows indicate the approximate injection times. All data points represent group means ± SEM; (*) significantly different from the value of group A; (#) significantly different from the value in session 16.
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fig1: Preconditioning ip injection of the D1/D5 agonist SKF-38393 into naïve gerbils improves learning, and presession ip injection of the D1/D5 antagonist SCH-23390 into well-trained gerbils impairs performance of the FM discrimination. Data were collected in Experiment 1. (A) Design of pharmacological treatment. Gerbils were randomly assigned to 1 of 2 groups, A and B, and trained on the FM discrimination task once per day for a total of 18 sessions. Training-free intervals of 2 days were interspersed after sessions 5, 10, and 15. Injections of vehicle (Veh), SKF-38393 (SKF; 5 mg/kg), or SCH-23390 (SCH; 0.1 mg/kg) were performed 30 min prior to the indicated training sessions. (B) Discrimination rates D per training session. Arrows indicate the approximate injection times. All data points represent group means ± SEM; (*) significantly different from the value of group A; (#) significantly different from the value in session 16.

Mentions: Experiment 1 was designed as a pilot study with only 4 gerbils per group for an initial assessment of the role of dopamine in FM discrimination learning and performance. To this end, presession intraperitoneal injections of the D1-like dopamine receptor agonist SKF-38393 and, later in the well-trained animals, of the D1-like dopamine receptor antagonist SCH-23390 were performed. Gerbils were randomly assigned to group A or B and trained on the FM discrimination task once per day for a total of 18 sessions with training-free intervals of 2 days after sessions 5, 10, and 15. The 2 groups were pharmacologically treated and behaviorally tested following the scheme of Figure 1A. The mean discrimination rates D calculated per group and training session are shown in Figure 1B.


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)

Preconditioning ip injection of the D1/D5 agonist SKF-38393 into naïve gerbils improves learning, and presession ip injection of the D1/D5 antagonist SCH-23390 into well-trained gerbils impairs performance of the FM discrimination. Data were collected in Experiment 1. (A) Design of pharmacological treatment. Gerbils were randomly assigned to 1 of 2 groups, A and B, and trained on the FM discrimination task once per day for a total of 18 sessions. Training-free intervals of 2 days were interspersed after sessions 5, 10, and 15. Injections of vehicle (Veh), SKF-38393 (SKF; 5 mg/kg), or SCH-23390 (SCH; 0.1 mg/kg) were performed 30 min prior to the indicated training sessions. (B) Discrimination rates D per training session. Arrows indicate the approximate injection times. All data points represent group means ± SEM; (*) significantly different from the value of group A; (#) significantly different from the value in session 16.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Preconditioning ip injection of the D1/D5 agonist SKF-38393 into naïve gerbils improves learning, and presession ip injection of the D1/D5 antagonist SCH-23390 into well-trained gerbils impairs performance of the FM discrimination. Data were collected in Experiment 1. (A) Design of pharmacological treatment. Gerbils were randomly assigned to 1 of 2 groups, A and B, and trained on the FM discrimination task once per day for a total of 18 sessions. Training-free intervals of 2 days were interspersed after sessions 5, 10, and 15. Injections of vehicle (Veh), SKF-38393 (SKF; 5 mg/kg), or SCH-23390 (SCH; 0.1 mg/kg) were performed 30 min prior to the indicated training sessions. (B) Discrimination rates D per training session. Arrows indicate the approximate injection times. All data points represent group means ± SEM; (*) significantly different from the value of group A; (#) significantly different from the value in session 16.
Mentions: Experiment 1 was designed as a pilot study with only 4 gerbils per group for an initial assessment of the role of dopamine in FM discrimination learning and performance. To this end, presession intraperitoneal injections of the D1-like dopamine receptor agonist SKF-38393 and, later in the well-trained animals, of the D1-like dopamine receptor antagonist SCH-23390 were performed. Gerbils were randomly assigned to group A or B and trained on the FM discrimination task once per day for a total of 18 sessions with training-free intervals of 2 days after sessions 5, 10, and 15. The 2 groups were pharmacologically treated and behaviorally tested following the scheme of Figure 1A. The mean discrimination rates D calculated per group and training session are shown in Figure 1B.

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