The amyloid-β precursor protein (APP) is a transmembrane protein constitutively expressed in the brain and highly implicated in Alzheimer’s disease aetiology. We previously identified a novel cleavage site of APP, the η-secretase site (Willem et al. Nature 2015, PMID:26322584). Peptides resulting from this cleavage and α- or β-secretase-dependent proteolysis are the extracellular soluble AETA peptides (Aη-α or Aη-β, respectively). Our previous work also demonstrated that AETA modulates synaptic plasticity and significantly reduces calcium activity in the hippocampus (HPC) in vivo. These results suggest that AETA may serves as an interesting modulator of hippocampal network activity, potentially influencing the dynamics of the neuronal network. To study the involvement of AETA in the regulation of neuronal networks, new mouse lines were used: The APPdelETA line, where η-secretase processing is abolished (no more AETA); and the AETA-m line, where human AETA is produced and secreted in the brain. In vivo electrophysiological studies using Local Field Potential (LFP) provide initial insights into how variations in AETA levels impact brain network activity in HPC and a long-range cortical connection, the Medial Prefrontal Cortex (mPFC). These initial results confirm that AETA modulates network activity, and in particular, the coupled activity between Theta and Gamma rhythms in both regions during REM sleep, a coupling already reported to be involved in memory processing (Bott et al. Cerebral Cortex 2016, PMID:26250776). To further understand the impact of AETA on neural network activity, we plan to record this neural network during memory tasks and sleep phases following these tasks.