title: Reduction of glutamate release probability and the number of releasable vesicles are required for suppression of glutamatergic transmission by β1-adrenoceptors in the medial prefrontal cortex.
abstract: The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation and behavioral inhibition. Microinjection of β1-adrenoceptor (β1-AR) agonist into the PFC has been shown to impair PFC cognitive function. However, the underlying cellular and molecular mechanisms have not been determined yet. In the present study, we tested the hypothesis that β1-AR mediated modulation of excitatory synaptic transmission contributes to PFC dysfunction. We found that 1) the β1-AR agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was mediated via decreasing release probability and the number of releasable vesicles. 4) Dobu suppressed inward currents evoked by puff application of glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study indicates that β1-AR activation suppresses excitatory synaptic transmission in medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our results may provide a cellular and molecular mechanism that helps explain β1-AR-induced PFC dysfunction.
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China. Electronic address: luofei@ncu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Institute of Neurobiology & State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Guo
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Si-Hai
authors.initials: SH
authors.lastname: Li
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004280:Dobutamine / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D018342:Receptors, Adrenergic, beta-1; D018698:Glutamic Acid; D004280:Dobutamine
keywords: Glutamatergic transmission; Medial prefrontal cortex; Rat; β(1)-Adrenoceptor