Hyperactivity of medial prefrontal cortex pyramidal neurons occurs in a mouse model of early-stage Alzheimer’s disease without β-amyloid accumulation

The normal function of the medial prefrontal cortex (mPFC) is essential for regulating neurocognition, but it disrupted in early stages Alzheimer’s disease (AD) before accumulation Aβ and appearance symptoms. Despite this, little known about how functional activity pyramidal neurons changes as progresses during aging. We used electrophysiological techniques (patch-clamping) to assess brain 3xTg-Alzheimer’s mice modeling early-stage without accumulation. Our results indicate that firing rate frequency spontaneous excitatory postsynaptic currents (sEPSCs) were significantly increased from young (4–5-month, equivalent <30-year-old humans) compared age-matched control mice. Blocking ionotropic glutamatergic NMDA receptors, which regulate neuronal excitability Ca 2+ homeostasis, abolished this hyperactivity. There no influx through voltage-gated channels (VGCCs) or inhibitory controls. Additionally, acute exposure Aβ42 potentiated hyperactivity had effects on These findings at induced by an abnormal increase presynaptic glutamate release receptor activity, initiates dyshomeostasis. because accumulated forms unconventional late stage disease, our study also suggests exacerbated dyshomeostasis following overactivation such VGCCs.