TNEA Regulates Hippocampal Oscillation by Improving Inhibitory Synaptic Plasticity to Ameliorates Cognitive Impairment in Alzheimer's Disease

Abstract Three‐needle electroacupuncture (TNEA) has demonstrated efficacy in improving cognitive function in both Alzheimer's disease (AD) model animals and patients, although its underlying mechanism remains unclear. Here this work investigates the potential connection between cognitive‐enhancing effect and TNEA in 5×familial Alzheimer disease（5xFAD) mice model, a model characterized by Amyloid‐beta (Aβ) pathology. This work finds alterations in gamma/theta oscillations and deficits in inhibitory monosynaptic transmission in the hippocampal CA1 region of AD. Parvalbumin‐positive (PV + ) interneurons are crucial for generating gamma oscillations and modulating theta oscillation, thereby maintaining the excitation‐inhibition (E/I) balance in local neural circuits. In 5xFAD mice, TNEA modulated PV + interneuron function, enhancing gamma oscillations during quiescent states. Furthermore, during the novel object recognition test (NORT), TNEA increased theta oscillation power by strengthening presynaptic inhibitory interneurons involved in monosynaptic connections. Collectively, these findings suggest TNEA is a viable minimally invasive treatment approach for AD.