Glutamate is the major excitatory neurotransmitter in the mammalian brain and is related to memory by calcium-conducting receptors. Neuregulins have emerged as long-term modulating molecules of synaptic signaling by glutamate receptors, playing a role in some cognition/memory-related disorders and moreover being part of transient functional microdomains, called lipid rafts. Here we characterize one specific isoform of neuregulin as a central biomarker for glutamate-related signaling, integrating results from in vitro and in vivo models by a differential functional and proteomic approach.