Since synaptic losses and axonal degeneration occur earlier than neuronal losses in prion diseases (Liberski and Budka, 1999; Reis et al., 2015; Sisková et al., 2009) and acute neurotoxicity caused by the induction of PrPC-dependent neurotoxic signals through PrPC-PrPSc interaction appears to be selective to excitatory synapse in the neuronal culture model (Fang et al., 2018; Foliaki et al., 2018), functional analyses of both excitatory and inhibitory neurons are needed to understand the precise neuropathogenesis. The gene discussed is PRNP; the disease is prion disease.