期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 85, 期 -, 页码 170-182出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2017.10.002
关键词
Neuropeptide; Neuronal nicotinic acetylcholine receptor; Excitatory postsynaptic current; Synaptic plasticity; Cell signaling; Gene transcription
资金
- National Science Foundation [0951549]
- University of Toledo Research Innovation Award
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [0951549] Funding Source: National Science Foundation
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr and Margiotta, 2016). At neuronal synapses where transmission is mediated by nicotinic acetylcholine receptors (nAChRs) transient PACAP exposure increases the frequency and amplitude (F-s and A(s)) of spontaneous excitatory postsynaptic currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high-affinity PACAP receptor (PAC(1)R) signaling via adenylate cyclase (AC), cyclic AMP (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release (Pugh et al., 2010; Jayakar et al., 2014). Remarkably, synaptic changes persist 48 h after transient PACAP exposure, featuring a similar increase in F-s and an even larger increase in A(s). Pharmacological studies reveal that this long-term (LT) plasticity requires PACAP/PAC(1)R signaling via AC and cAMP, but unlike ST plasticity, Phospholipase-C and new gene transcription are also necessary, whereas PKA, nAChR, impulse and NO synthase (NOS1) activities are dispensable. In accord with the increases in F-s and A(s) characterizing LT plasticity, miniature EPSC (mEPSC) frequency, ACh release (quantal content), and mEPSC amplitude (quantal size) all increased in parallel. Consistent with these functional changes, imaging studies reveal that LT, but not ST, PACAP-induced plasticity is accompanied by increases in presynaptic terminal size, postsynaptic nAChR cluster size and density, and the size and density of co-localized pre- and post-synpatic sites. Thus PACAP/PAC(1)R signaling induces mechanistically distinct forms of synaptic plasticity, with a ST form arising from acute, membrane-delimited processes, and a LT form arising from transcription-dependent alterations in the function and structural arrangement of pre- and post-synaptic components.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据