title: Both pre- and post-synaptic alterations contribute to aberrant cholinergic transmission in superior cervical ganglia of APP(-/-) mice.
abstract: Though amyloid precursor protein (APP) can potentially be cleaved to generate the pathological amyloid β peptide (Aβ), APP itself plays an important role in regulating neuronal activity. APP deficiency causes functional impairment in cholinergic synaptic transmission and cognitive performance. However, the mechanisms underlying altered cholinergic synaptic transmission in APP knock-out mice (APP(-/-)) are poorly understood. In this study, we conducted in vivo extracellular recording to investigate cholinergic compound action potentials (CAPs) of the superior cervical ganglion (SCG) in APP(-/-) and littermate wild-type (WT) mice. Our results demonstrate that APP not only regulates presynaptic activity, but also affects postsynaptic function at cholinergic synapses in SCG. APP deficiency reduces the number of vesicles in presynaptic terminalsand attenuatesthe amplitude of CAPs, likely due to dysfunction of high-affinity choline transporters. Pharmacological and biochemical examination showed that postsynaptic responsesmediated by α4β2 and α7 nicotinic acetylcholine receptors are reduced in the absence of APP. Our research provides evidences on how APP regulates cholinergic function and therefore may help to identify potential therapeutic targets to treat cholinergic dysfunction associated with Alzheimer's disease pathogenesis.
authors.affiliation: School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
authors.forename: Zhao-Lin
authors.initials: ZL
authors.lastname: Cai
authors.affiliation: School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
authors.forename: Jin-Zhao
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.affiliation: School of Psychology, South China Normal University, Guangzhou 510631, PR China; Brain Science Institute, South China Normal University, Guangzhou 510631, PR China; Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou 510631, PR China; Center for Studies of Psychological Application, South China Normal University, Guangzhou 510631, PR China. Electronic address: yangli08@scnu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Life Sciences, South China Normal University, Guangzhou 510631, PR China; Brain Science Institute, South China Normal University, Guangzhou 510631, PR China. Electronic address: longcheng@scnu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Long
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology; D005124:Eye Abnormalities / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D018678:Cholinergic Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine
keywords: Amyloid precursor protein; Cholinergic synaptic transmission; High-affinity choline transporter; Nicotinic acetylcholine receptor; Superior cervical ganglia