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Improvement of Two-Way Active Avoidance Memory Requires Protein Kinase A Activation and Brain-Derived Neurotrophic Factor Expression in the Dorsal Hippocampus

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Abstract

Previous studies have shown that two-way active avoidance (TWAA) memory processing involves a functional interaction between the pontine wave (P wave) generator and the CA3 region of the dorsal hippocampus (DH-CA3). The present experiments examined whether the interaction between P wave generator activity and the DH-CA3 involves the intracellular protein kinase A (PKA) signaling system. In the first series of experiments, rats were subjected to a session of TWAA training followed immediately by bilateral microinjection of either the PKA activation inhibitor (KT-5720) or vehicle control into the DH-CA3 and tested for TWAA memory 24 h later. The results indicated that immediate KT-5720 infusion impaired improvement of TWAA performance. Additional experiments showed that KT-5720 infusion also blocked TWAA training-induced BDNF expression in the DH-CA3. Together, these findings suggest that the PKA activation and BDNF expression in the DH-CA3 is essential for the improvement of TWAA memory.

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Abbreviations

Arc:

activity-regulated cytoskeletal-associated protein

BDNF:

brain-derived neurotrophic factor

CREB:

cAMP response element-binding protein

DD-T:

drug—training

DD-TT:

drug—training and test

DH-CA3:

CA3 region of the dorsal hippocampus

P wave:

pontine wave

PKA:

protein kinase A

REM:

rapid eye movement

SC-CC:

saline control—cage control

SC-T:

saline control—training

SC-TT:

saline control—training and test

SWS:

slow-wave sleep

TWAA:

two-way active avoidance

W:

wakefulness

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Acknowledgements

We thank Dr. Edward Stack for his critical reading and valuable discussion on this manuscript. This study was supported by NIH research grants (NS 34004 and MH 59839) to Subimal Datta.

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  1. Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, Boston University School of Medicine, 85 East Newton Street, Suite: M-902, Boston, MA, 02118, USA

    Subimal Datta, Donald F. Siwek & Max P. Huang

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  1. Subimal Datta
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  2. Donald F. Siwek
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  3. Max P. Huang
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Correspondence to Subimal Datta.

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Datta, S., Siwek, D.F. & Huang, M.P. Improvement of Two-Way Active Avoidance Memory Requires Protein Kinase A Activation and Brain-Derived Neurotrophic Factor Expression in the Dorsal Hippocampus. J Mol Neurosci 38, 257–264 (2009). https://doi.org/10.1007/s12031-009-9206-7

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