Reduced firing rates of pyramidal cells in frontal cortex of APP/PS1 can be restored by acute treatment with levetiracetam

Abstract

In recent years aberrant neural oscillations in various cortical areas have emerged as a common physiological hallmark across mouse models of amyloid pathology and patients with Alzheimers disease. However, much less is known about the underlying effect of amyloid pathology on single cell activity. Here, we used high density silicon probe recordings from frontal cortex area of 9 months old APP/PS1 mice to show that resting state Local Field Potential (LFP) power in the theta and beta band is increased in transgenic animals, while single cell firing rates, specifically of putative pyramidal cells, are significantly reduced. At the same time, these sparsely firing pyramidal cells phase-lock their spiking activity more strongly to the ongoing theta and beta rhythms. Furthermore, we demonstrated that the anti-epileptic drug, levetiracetam, can restore principal cell firing rates back to control levels. Overall, our results highlight reduced firing rates of cortical pyramidal cells as a symptom of amyloid pathology and indicate that lifting cortical inhibition might contribute to the beneficial effects of levetiracetam on AD patients.\n\nO_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY