An Optogenetic Study of the Electrophysiological Properties of Hippocampal Neurons in PS1-M146V Transgenic Mice (a model of Alzheimer’s disease)

We report here a comparative (using chemical, electrical, and optical stimulation) study of the electrophysiological properties of cultured hippocampal neurons from transgenic animals expressing a mutant presenilin 1 protein. All three types of stimulation were found to elicit the following differences from the wild type: with overall more active electrophysiological behavior (especially at the beginning of stimulation), mutant cells differed from wild-type neurons by not maintaining consistent activity over time. However, only optogenetic stimulation increased the absolute number of action potentials and decreased their amplitude as compared with the corresponding values in wild-type neurons. The molecular-cellular mechanisms of this effect are suitable for further studies, both basic and applied (to identify regimes for controlling the electrical activity of neurons).