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Canonical JAK‐STAT signaling is pivotal for long‐term depression at adult hippocampal temporoammonic‐CA1 synapses
Author(s) -
McGregor Gemma,
Irving Andrew J.,
Harvey Jenni
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601293rr
Subject(s) - hippocampal formation , term (time) , stat , neuroscience , jak stat signaling pathway , depression (economics) , medicine , biology , signal transduction , receptor , microbiology and biotechnology , physics , economics , stat3 , macroeconomics , quantum mechanics , tyrosine kinase
The Janus kinase (JAK)‐signal transducer and activator of transcription (STAT) signaling pathway is involved in numerous cellular processes and it is implicated in neurodegenerative disorders, like Alzheimer disease. Recent studies identified a crucial role for this pathway in activity‐dependent long‐term depression (LTD) at hippocampal Schaffer collateral (SC)‐CA1 synapses. However, it is unclear whether JAK‐STAT signaling also regulates excitatory synaptic function at the anatomically distinct temporoammonic (TA) input to CA1 neurons. Here we demonstrate that LTD at adult TA‐CA1 synapses involves JAK‐STAT signaling, but unlike SC‐CA1 synapses, requires rapid gene transcription. TA‐CA1 LTD requires NMDA receptor activation and is independent of PI3K or ERK signaling. JAK‐STAT signaling was critical for TA‐CA1 LTD as inhibition of JAK or STAT blocked LTD induction and prevented NMDA‐induced AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) receptor internalization in hippocampal neurons. Moreover, an increase in phosphorylated JAK2 and STAT3 accompanied chemical induction of LTD and AMPA receptor internalization. STAT3‐driven gene transcription was required for LTD as inhibition of STAT3‐DNA binding, nuclear export, and gene transcription all prevented LTD induction. These data indicate an essential role for canonical JAK‐STAT signaling in activity‐dependent LTD at TA‐CA1 synapses and provide valuable insight into the role of the TA input in hippocampal synaptic plasticity.—McGregor, G., Irving, A. J., Harvey, J. Canonical JAK‐STAT signaling is pivotal for long‐term depression at adult hippocampal temporoammonic‐CA1 synapses. FASEB J . 31, 3449–3466 (2017). www.fasebj.org