title: Alterations of the electrophysiological properties from cortical layer 5 pyramidal neurons in temporary rapamycin-treated rodent brain slices.
abstract: The mammalian target of rapamycin (mTOR) signaling pathway is involved in neuro-developmental/degenerative and neuropsychiatric abnormalities. Rapamycin, a specific and potent inhibitor of mTOR signaling, could regulate synaptic plasticity and synaptic transmission of glutamatergic neurons following prolonged treatment. Its immediate effects on electrophysiological properties of cortical layer 5 (L5) pyramidal neurons where the information undergoes a sophisticated processing remain unknown. Here, we found that acute (within 2min) bath-application of rapamycin (0.5μgml(-1)) was able to depolarize the current-clamp baseline potentials significantly at postnatal day (P) 4, P10 in rats and P90 in mice (P<0.05), and altered the membrane current/voltage (I/V) curves in an age-dependent manner. Rapamycin not only increased the standard deviation or the peak amplitude of baseline membrane potential, but also increased the frequencies of spontaneous action potentials in more mature neurons (P10 and P90). In addition, rapamycin decreased the burst-firing frequencies of cortical L5 burst-spiking neurons from mature brains, and further switched their firing modes to regular-spiking ones. These findings suggest that acute inhibition of mTOR signaling by rapamycin induces an immediate impact on L5 pyramidal neurons' electrophysiological properties, indicating that its effects might involve mechanisms of ion channel's regulation.
authors.affiliation: Department of Neurology, The Children's Hospital Zhejiang University School of Medicine, 57 Zhugan Lane, Yanan Road, Hangzhou 310003, China.
authors.forename: Keming
authors.initials: K
authors.lastname: Ren
authors.affiliation: Department of electroencephalogram, The Children's Hospital Zhejiang University School of Medicine, 57 Zhugan Lane, Yanan Road, Hangzhou 310003, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Children's Hospital Zhejiang University School of Medicine, 57 Zhugan Lane, Yanan Road, Hangzhou 310003, China.
authors.forename: Guoxia
authors.initials: G
authors.lastname: Sheng
authors.affiliation: Department of rehabilitation, The Children's Hospital Zhejiang University School of Medicine, 57 Zhugan Lane, Yanan Road, Hangzhou 310003, China.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Stark Neurosciences Research Institute Indiana University School of Medicine, 980 W. Walnut Street, R3, Room C432A, Indianapolis, IN 46202, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Neurology, The Children's Hospital Zhejiang University School of Medicine, 57 Zhugan Lane, Yanan Road, Hangzhou 310003, China; Department of Laboratory, The Children's Hospital Zhejiang University School of Medicine, 57 Zhugan Lane, Yanan Road, Hangzhou 310003, China. Electronic address: jiangkw_zju@zju.edu.cn.
authors.forename: Kewen
authors.initials: K
authors.lastname: Jiang
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Brain development; Cortical layer 5 pyramidal neuron; Electrophysiology; Rapamycin; mTOR signaling