title: Neuronal network activity in the hippocampus of tau transgenic (Tg4510) mice.
abstract: Development of neurofibrillary tangles in Alzheimer's disease correlates with neuronal loss and dementia. Transgenic Tg4510 mice model the tauopathy of the disease, with these mice exhibiting progressive, region-specific neuronal loss, and behavioral deficits. In the present study, neuronal network activity in the hippocampus of 7-month-old Tg4510 mice was investigated and compared with age-matched wild-type (WT) mice. Multisite field potentials were recorded using 16-site silicon probes, inserted across the hippocampus in urethane anesthetized mice. The hippocampal network theta oscillation was evaluated in these mice by stimulating the brainstem nucleus pontis oralis. Subsequently, population spikes in the dentate gyrus were identified in response to perforant path stimulation, and long-term potentiation was elicited by theta burst stimulation. Tg4510 mice showed dramatically reduced dentate gyrus population spike amplitude; however, the magnitude of theta burst stimulation-induced long-term potentiation was identical in WT and transgenic mice. WT and Tg4510 mice showed identical increase in frequency to nucleus pontis oralis stimulation, whereas absolute theta power was severely reduced in the Tg4510 animals. Because total signal power over the entire frequency band range was reduced, there was no difference in relative theta power between WT and Tg4510 mice. These presently described electrophysiological findings can be directly attributed to the drastic reduction of pyramidal/granule neurons in Tg4510 mice, which could be the main contributing factor to their impaired behavior and cognitive function. However, the remaining synapses and neuronal circuitry seem to function properly in these assays.
authors.affiliation: Neuroscience Research Unit, Pfizer Global Research and Development, Cambridge, MA, USA. Electronic address: liam.scott@pfizer.com.
authors.forename: Liam
authors.initials: L
authors.lastname: Scott
authors.affiliation: Neuroscience Research Unit, Pfizer Global Research and Development, Cambridge, MA, USA.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
authors.affiliation: Neuroscience Research Unit, Pfizer Global Research and Development, Cambridge, MA, USA.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Kawabe
authors.affiliation: Neuroscience Research Unit, Pfizer Global Research and Development, Cambridge, MA, USA.
authors.forename: Mihály
authors.initials: M
authors.lastname: Hajós
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D018891:Dentate Gyrus / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D017774:Long-Term Potentiation; D008297:Male; D008822:Mice, Transgenic; D009415:Nerve Net / Q000473:pathology* / Q000503:physiopathology*; D024801:Tauopathies / Q000473:pathology / Q000503:physiopathology; D013826:Theta Rhythm
keywords: Alzheimer's disease; Electrophysiology; Long-term potentiation; Neurodegeneration; Theta oscillation