Journal of Alzheimer's disease : JAD · 2021
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.
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Zhang Xiao-Qin, Xu Le, Yang Si-Yu, Hu Lin-Bo, Dong Fei-Yuan, Sun Bing-Gui, Shen Hao-Wei
Аннотация
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.
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.