This change appears to require the local upregulation of TNFα, an established mediator of HSP (Lewitus et al., 2014), and serves to maintain the strength of output from spiny neurons that would otherwise be pathologically enhanced by the loss of heterosynaptic D2R-mediated inhibition accompanying the loss of dopaminergic afferents (Figure 2A). The gene discussed is TNF; the disease is hereditary spastic paraplegia.