DJ-1 is essential for long-term depression at hippocampal CA1 synapses.

Mutations in DJ-1 cause inherited Parkinson's disease (PD) in several families. The normal function of DJ-1 is unknown, but mice lacking DJ-1 exhibit a deficit in dopaminergic signaling in the striatum. Since the hippocampus contains relatively high levels of DJ-1, and PD patients are often cognitively impaired, we evaluated the effects of DJ-1 deficiency on the plasticity of hippocampal CA1 synapses. LTP was slightly impaired and LTD was abolished in DJ-1-/- mice, whereas DJ-1+/- mice exhibited no alterations in synaptic plasticity. The dopamine receptor D2/3 agonist quinpirole rescued LTD in DJ-1-/- mice, suggesting a role for impaired dopaminergic signaling in the hippocampal LTD deficit.