Young DAPK1 knockout mice have altered pre-synaptic function.

The death associated protein kinase 1 (DAPK1) has recently been shown to have a physiological function in long-term depression (LTD) of glutamatergic synapses: Acute inhibition of DAPK1 blocked the LTD that is normally seen at the hippocampal CA1 synapse in young mice, and a pharmacogenetic combination approach showed that this specifically required DAPK1-mediated suppression of post-synaptic CaMKII binding to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B during LTD stimuli. Surprisingly, we found here that genetic deletion of DAPK1 (in DAPK1-/- mice) did not reduce LTD. Paired pulse facilitation experiments indicated a pre-synaptic compensation mechanism: in contrast to wild type mice, LTD stimuli in DAPK1-/- mice decreased pre-synaptic release probability. Basal synaptic strength was normal in young DAPK1-/- mice, but basal glutamate release probability was reduced, an effect that normalized with maturation.