BDNF Facilitates L-LTP Maintenance in the Absence of Protein Synthesis through PKMζ

Late-phase long term potentiation (L-LTP) is thought to be the cellular basis for long-term memory (LTM). While LTM as well as L-LTP is known to depend on transcription and translation, it is unclear why brain-derived neurotrophic factor (BDNF) could sustain L-LTP when protein synthesis is inhibited. The persistently active protein kinase zeta (PKM zeta) is the only molecule implicated in perpetuating L-LTP maintenance. Here, in mouse acute brain slices, we show that inhibition of PKM zeta reversed BDNF-dependent form of L-LTP. While BDNF did not alter the steady-state level of PKM zeta, BDNF together with the L-LTP inducing theta-burst stimulation (TBS) increased PKM zeta level even without protein synthesis. Finally, in the absence of de novo protein synthesis, BDNF maintained TBS-induced PKM zeta at a sufficient level. These results suggest that BDNF sustains L-LTP through PKM zeta in a protein synthesis-independent manner, revealing an unexpected link between BDNF and PKM zeta.