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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

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Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal

Clair A Booth¹, Jonathan Witton¹, Jakub Nowacki²

¹School of Physiology and Pharmacology and.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience

|January 14, 2016

Summary

Tau protein aggregates in the brain disrupt hippocampal function, impairing spatial memory in dementia. This study reveals cellular and network changes linked to tau pathology, offering potential therapeutic targets for cognitive decline.

Keywords:

GABA intrinsic properties place cell resonance synaptic plasticity

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An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons

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Published on: May 23, 2019

Area of Science:

Neuroscience
Cellular and Molecular Biology
Neurodegenerative Diseases

Background:

Tau protein aggregate formation is linked to cognitive decline in dementia.
The hippocampus is crucial for memory and is affected early in dementia.
Understanding tau's impact on hippocampal function is vital for dementia research.

Purpose of the Study:

To investigate the effects of tau pathology on hippocampal neuronal function in the rTg4510 mouse model.
To correlate cellular neurophysiology changes with network function and spatial memory deficits.

Main Methods:

Utilized in vivo and in vitro electrophysiological recordings in rTg4510 transgenic mice.
Examined CA1 pyramidal neuron properties, synaptic transmission, and network oscillations.
Assessed spatial information coding in relation to tau pathology.

Main Results:

Observed shifted theta-frequency resonance in CA1 pyramidal neurons.
Identified deficits in synaptic transmission and impaired plasticity at hippocampal synapses.
Found aberrant CA1 network oscillations, pyramidal neuron bursting, and disrupted spatial information coding.

Conclusions:

Tau pathology in the hippocampus causes specific disturbances at synaptic, cellular, and network levels.
Aberrant hippocampal function leads to impaired spatial information encoding and memory deficits.
Findings suggest novel therapeutic targets for dementia by addressing tau-induced hippocampal dysfunction.