Reduced Synaptic Transmission and Intrinsic Excitability of a Subtype of Pyramidal Neurons in the Medial Prefrontal Cortex in a Mouse Model of Alzheimer’s Disease
Affiliations: [a] Department of Pharmacology, School of Medicine, Zhejiang Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang, China
| [b] Key Laboratory of Addiction Research of Zhejiang Province, Ningbo Kangning Hospital, Ningbo, Zhejiang,
China
| [c] Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
Correspondence:
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Correspondence to: Xiao-Qin Zhang and Hao-Wei Shen, Department of Pharmacology, School of Medicine, Zhejiang Key Laboratory of Pathophysiology, Ningbo University, 818 Fenghua Rd, Ningbo, Zhejiang, 315211, China. E-mails: zhangxiaoqin1@nbu.edu.cn, shenhaowei@nbu.edu.cn.
Note: [1] These authors contributed equally to this work.
Abstract: Background:Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer’s disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to cortical or subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. Objective:To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. Methods:The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. Results:We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. Conclusion:These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.
