Successful memory encoding and information storage require specific patterns of synchronous activity in neural circuits and networks. These processes rely on the accurate equilibrium between excitatory and inhibitory neurotransmission systems driven by different neuronal types. During preclinical stages of Alzheimer’s disease (AD), there is an imbalance between both systems mainly due to synaptic dysfunction induced by amyloid-β (Aβ) peptide. Prior to accumulation of the histopathological hallmarks of the disease, this scenario leads to hippocampal hyperexcitability, disrupted oscillatory activity patterns and cognitive deficits. The molecular mechanisms underlying these alterations remain unclear but functional evidence point to alteration of neuronal excitability playing a pivotal role in early Aβ-induced AD pathogenesis. Previously, Aβ25-35 has been proposed as the biologically active fragment of Aβ, and has been shown to induce major neuropathological signs related to early AD stages. Unlike other Aβ isoforms with high clinical relevance such as Aβ1-42, Aβ25-35 does not form ion-permeable pores in neuronal membrane. Although it has been extensively used to explore acutely the pathophysiological events related with neuronal dysfunction induced by soluble Aβ forms, it is still unknown whether its toxic effects on hippocampal performance mimic the actions of other clinically relevant species. Here, we have systematically examined the effects of Aβ25-35 on the physiological role of the hippocampus at different complexity levels (from synaptic to behavioral levels), with special emphasis on synaptic plasticity processes. Mice were prepared for chronic intracerebroventricular injections, hippocampal electrical stimulation and electrophysiological recordings in vivo to correlate neural activity to hippocampal-dependent learning and memory tasks such as novel object recognition and open field habituation tests. Our data reveals that Aβ25-35 alters hippocampal synaptic properties (excitability and synaptic plasticity) and triggers an imbalance in the excitatory/inhibitory neurotransmission that causes aberrant network activity and early cognitive impairments with high similarities to Aβ1-42 effects. Thus, our results confirm the potentiality of the model to study preclinical stages of hippocampal amyloidopathy at the molecular, synaptic, circuit, and behavioral levels.