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SYNAPTIC ACTIVITY AND MORPHOLOGY OF HUMAN NEURONS IN ACUTE SLICES OF FRONTAL CORTEX BIOPSIES OF PATIENTS WITH ALZHEIMER’S DISEASE PATHOLOGY
Abstract
Aims
Most electrophysiological studies on Alzheimer's Disease (AD) have been performed using AD mouse models. The electrophysiological properties of neurons in the human AD brain have not been described due to the lack of suitable material for such investigations.
Methods
Here we describe, using the whole-cell patch-clamp technique in acute slices, the electrophysiological properties of human neurons in cortical biopsies obtained from idiopathic normal pressure hydrocephalus patients undergoing shunt surgery. Due to the beta-amyloid and tau pathology present in the subpopulation of these biopsies, they offer a tissue model for investigation on how AD-related pathology affects neuronal operational properties in the human brain.
Results
We recorded several neuronal parameters including sodium and potassium currents, the shape and action potential firing pattern, and spontaneous post-synaptic activity of both pyramidal cells and fast-firing parvalbumin interneurons in these biopsies. We found alterations in the excitation and inhibition balance in neurons in biopsies with AD-related pathology. Morphological reconstruction of the recorded neurons filled with biocytin revealed alterations in the spine density in neurons recorded in biopsies with AD-related pathology.
Conclusions
This is the first study to report the impact of AD-related pathology on single-neuron operational properties and morphology. Our integrative analysis of human neuronal electrophysiology and subsequent cell morphology reconstruction allows us to register primary pathological changes in neuronal functions in correlation with spine distribution impacted by AD pathology.