Open AccessYoung DAPK1 knockout mice have altered presynaptic function
Author(s) -
Dayton J. Goodell,
Jonathan E. Tullis,
K. Ulrich Bayer
Publication year - 2021
Publication title -
journal of neurophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.302
H-Index - 245
eISSN - 1522-1598
pISSN - 0022-3077
DOI - 10.1152/jn.00055.2021
Subject(s) - nmda receptor , glutamate receptor , ampa receptor , knockout mouse , biology , postsynaptic potential , neuroscience , excitatory postsynaptic potential , protein kinase a , synapse , microbiology and biotechnology , synaptic plasticity , glutamatergic , kinase , receptor , biochemistry , inhibitory postsynaptic potential
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 postsynaptic Ca 2+ /calmodulin-dependent protein kinase II 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 presynaptic compensation mechanism: in contrast to wild-type mice, LTD stimuli in DAPK1 -/- mice decreased presynaptic release probability. Basal synaptic strength was normal in young DAPK1 -/- mice, but basal glutamate release probability was reduced, an effect that normalized with maturation. NEW & NOTEWORTHY Young death-associated protein kinase 1 (DAPK1) knockout mice have reduced basal glutamate release probability, an effect that normalized with maturation. This provided a compensatory mechanism that may have prevented a reduction of long-term depression in the young DAPK1 knockout mice.