PMID- 29017814
OWN - NLM
STAT- MEDLINE
DCOM- 20180725
LR  - 20220318
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 85
DP  - 2017 Dec
TI  - Pituitary adenylate cyclase activating polypeptide induces long-term, 
      transcription-dependent plasticity and remodeling at autonomic synapses.
PG  - 170-182
LID - S1044-7431(17)30241-5 [pii]
LID - 10.1016/j.mcn.2017.10.002 [doi]
AB  - 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 48h 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Starr, Eric R
AU  - Starr ER
AD  - Department of Neurosciences, University of Toledo, College of Medicine & Life 
      Sciences, United States.
FAU - Margiotta, Joseph F
AU  - Margiotta JF
AD  - Department of Neurosciences, University of Toledo, College of Medicine & Life 
      Sciences, United States. Electronic address: Joseph.Margiotta@Utoledo.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20171007
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (Receptors, Nicotinic)
SB  - IM
MH  - Animals
MH  - Autonomic Nervous System/metabolism
MH  - Chick Embryo
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Neuronal Plasticity/*physiology
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide/*metabolism
MH  - Receptors, Nicotinic/metabolism
MH  - Signal Transduction/*physiology
MH  - Synapses/*metabolism
MH  - Synaptic Transmission/physiology
OTO - NOTNLM
OT  - Cell signaling
OT  - Excitatory postsynaptic current
OT  - Gene transcription
OT  - Neuronal nicotinic acetylcholine receptor
OT  - Neuropeptide
OT  - Synaptic plasticity
EDAT- 2017/10/12 06:00
MHDA- 2018/07/26 06:00
CRDT- 2017/10/12 06:00
PHST- 2017/07/07 00:00 [received]
PHST- 2017/09/19 00:00 [revised]
PHST- 2017/10/06 00:00 [accepted]
PHST- 2017/10/12 06:00 [pubmed]
PHST- 2018/07/26 06:00 [medline]
PHST- 2017/10/12 06:00 [entrez]
AID - S1044-7431(17)30241-5 [pii]
AID - 10.1016/j.mcn.2017.10.002 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2017 Dec;85:170-182. doi: 10.1016/j.mcn.2017.10.002. Epub 2017 
      Oct 7.