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Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats
- Source :
- Learningmemory (Cold Spring Harbor, N.Y.). 20(5)
- Publication Year :
- 2013
-
Abstract
- The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation, behavioral inhibition, as well as memory storage. The functions of PFC are very sensitive to norepinephrine (NE), and even low levels of endogenously released NE exert a dramatic influence on the functioning of the PFC. Activation of β-adrenoceptors (β-ARs) facilitates synaptic potentiation and enhances memory in the hippocampus. However, little is known regarding these processes in the PFC. In the present study, we investigate the role of β2-AR in synaptic plasticity and behavioral memory. Our results show that β2-AR selective agonist clenbuterol facilitates spike-timing-dependent long-term potentiation (tLTP) under the physiological conditions with intact GABAergic inhibition, and such facilitation is prevented by co-application with the cAMP inhibitor Rp-cAMPS. Loading postsynaptic pyramidal cells with Rp-cAMPS, the PKA inhibitor PKI5-24, or the G protein inhibitor GDP-β-S significantly decreases, but does not eliminate, the effect of clenbuterol. Clenbuterol suppresses the GABAergic transmission, while blocking GABAergic transmission by the GABAA receptor blocker partially mimics the effect of clenbuterol. In behavioral tests, a post-training infusion of clenbuterol into mPFC enhances 24-h trace fear memory. In summary, we observed that prefrontal cortical β2-AR activation by clenbuterol facilitates tLTP and enhances trace fear memory. The mechanism underlying tLTP facilitation involves stimulating postsynaptic cAMP-PKA signaling cascades and suppressing GABAergic circuit activities.
- Subjects :
- Cognitive Neuroscience
Long-Term Potentiation
Hippocampus
Prefrontal Cortex
Synaptic Transmission
Cellular and Molecular Neuroscience
Postsynaptic potential
Memory
Cyclic AMP
Animals
Clenbuterol
Prefrontal cortex
Adrenergic beta-2 Receptor Agonists
Working memory
Chemistry
Pyramidal Cells
Excitatory Postsynaptic Potentials
Long-term potentiation
Cyclic AMP-Dependent Protein Kinases
Rats
Neuropsychology and Physiological Psychology
Synaptic plasticity
Synapses
GABAergic
Memory consolidation
Receptors, Adrenergic, beta-2
Neuroscience
Signal Transduction
Subjects
Details
- ISSN :
- 15495485
- Volume :
- 20
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Learningmemory (Cold Spring Harbor, N.Y.)
- Accession number :
- edsair.doi.dedup.....6d75ef81ba7f8d490bc646188d6c8778