We first observed that lentivirally mediated astrocyte-specific GADD34 expression in prion-diseased mice resulted in a significant and sustained improvement in burrowing behavior (Figure 6A), a motivational task sensitive to hippocampal (notably CA1) integrity that correlates with early synaptic dysfunction in prion disease (Deacon et al., 2001, Mallucci et al., 2007). This evidence concerns the gene PPP1R15A and prion disease.