Deficits of synaptic functions in hippocampal slices prepared from aged mice null α7 nicotinic acetylcholine receptors.
Alpha 7 (α7) nicotinic acetylcholine receptor (α7-nAChR) is one of most high expressed nAChR subtypes in the brain. The activation of nAChRs enhances animal cognitive, learning and memory abilities. However, the role of genetic knockout (KO) of α7-nAChRs in animal cognition-associated behaviors is still obscure. An early report showed that α7-nAChR KO mice did not exhibit behavioral phenotypes, concerning the roles of α7-nAChRs in normal, cognition-associated behaviors. Later, α7-nAChR KO mice were found a deficit in animal spatial discrimination. The roles of α7-nAChRs in the alterations of hippocampal synaptic function during aging process are largely unknown. Here, we address this question by examining synaptic function using field potential recording in hippocampal slice preparations from adult (12-14 months old) and aged (22-24 months old) α7-nAChR KO and age-matched wild-type (WT) mice. We found that compared to aged WT mice, aged α7-nAChR KO mice exhibited significantly reduced size of evoked field synaptic potential and impaired long-term potentiation (LTP) in hippocampal CA3-CA1 synapses. However, adult α7-nAChR KO mice did not show a clear deficit in LTP although the basic synaptic transmission was also reduced compared to adult WT mice. In both age groups, there was no significant difference of paired-pulse facilitation between α7-nAChR KO and WT mice. Collectively, this study provides direct evidence, for the first time, that the impaired synaptic function occurs in aged α7-nAChR KO mice, suggesting an importance of α7-nAChRs in maintaining cognitive function during aging process.
Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China; Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Luyao
L
Ma
Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Dharshaun
D
Turner
Departments of Physiology and Pharmacology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
Junfang
J
Zhang
Departments of Physiology and Pharmacology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
Qingwen
Q
Wang
Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Michele
M
Wang
Department of Physiology, Shantou University of Medical College, Shantou, Guangdong 515041, China.
Jianxing
J
Shen
Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address: Shijiangzhang@hotmail.com.
Shijiang
S
Zhang
Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA; Departments of Physiology and Pharmacology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China; Department of Physiology, Shantou University of Medical College, Shantou, Guangdong 515041, China. Electronic address: jie.wu@dignityhealth.org.
Jie
J
Wu
D000375:Aging / Q000502:physiology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D051379:Mice; D018345:Mice, Knockout; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000378:metabolism*
D064569:alpha7 Nicotinic Acetylcholine Receptor
Aging; Electrophysiology; Hippocampal slice; Long-term potentiation; Nicotinic acetylcholine receptor (nAChR); α7-nAChR