Optogenetic control of spine-head JNK reveals a role in dendritic spine regression

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Patrik Hollos, Jismi M. John, Jukka V. Lehtonen, Eleanor T. Coffey
Förläggare: Society for Neuroscience
Publiceringsår: 2020
Tidskrift: eNeuro
Volym: 7
Nummer: 1
eISSN: 2373-2822


In this study, we use an optogenetic inhibitor of JNK in dendritic spine
sub-compartments of rat hippocampal neurons. JNK inhibition exerts
rapid (within seconds) reorganisation of actin in the spine-head. Using
real-time FRET to measure JNK activity, we find that either excitotoxic
insult (NMDA) or endocrine stress (corticosterone), activate spine-head
JNK causing internalization of AMPARs and spine retraction. Both events
are prevented upon optogenetic inhibition of JNK, and rescued by JNK
inhibition even 2 h after insult. Moreover, we identify that the
fast-acting anti-depressant ketamine reduces JNK activity in hippocampal
neurons suggesting that JNK inhibition may be a downstream mediator of
its anti-depressant effect. In conclusion, we show that JNK activation
plays a role in triggering spine elimination by NMDA or corticosterone
stress, whereas inhibition of JNK facilitates regrowth of spines even in
the continued presence of glucocorticoid. This identifies that JNK acts
locally in the spine-head to promote AMPAR internalization and spine
shrinkage following stress, and reveals a protective function for JNK
inhibition in preventing spine regression.


Kinase, neuronal plasticity, optogenetics, stress


Senast uppdaterad 2020-20-09 vid 06:16