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Hippocampal 5‐HT 7 receptors signal phosphorylation of the GluA1 subunit to facilitate AMPA receptor mediated‐neurotransmission in vitro and in vivo
Author(s) -
Andreetta Filippo,
Carboni Lucia,
Grafton Gillian,
Jeggo Ross,
Whyment Andrew D,
Top Marco,
Hoyer Daniel,
Spanswick David,
Barnes Nicholas M
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13432
Subject(s) - ampa receptor , neurotransmission , hippocampal formation , sgk1 , neuroscience , receptor , biology , enzyme linked receptor , glutamatergic , long term depression , microbiology and biotechnology , chemistry , phosphorylation , glutamate receptor , biochemistry
Background and Purpose The 5‐HT 7 receptor is a GPCR that is the target of a broad range of antidepressant and antipsychotic drugs. Various studies have demonstrated an ability of the 5‐HT 7 receptor to modulate glutamatergic neurotransmission and cognitive processes although the potential impact upon AMPA receptors has not been investigated directly. The purposes of the present study were to investigate a direct modulation of the GluA1 AMPA receptor subunit and determine how this might influence AMPA receptor function. Experimental Approach The influence of pharmacological manipulation of the 5‐HT 7 receptor system upon phosphorylation of GluA1 subunits was assessed by Western blotting of fractionated proteins from hippocampal neurones in culture (or proteins resident at the neurone surface) and the functional impact assessed by electrophysiological recordings in rat hippocampus in vitro and in vivo . Key Results 5‐HT 7 receptor activation increased cAMP and relative pCREB levels in cultures of rat hippocampal neurones along with an increase in phosphorylation (Ser845) of the GluA1 AMPA receptor subunit evident in whole neurone extracts and within the neurone surface compartment. Electrophysiological recordings in rat hippocampus demonstrated a 5‐HT 7 receptor‐mediated increase in AMPA receptor‐mediated neurotransmission in vitro and in vivo . Conclusions and Implications The 5‐HT 7 receptor‐mediated phosphorylation of the GluA1 AMPA receptor provides a molecular mechanism consistent with the 5‐HT 7 receptor‐mediated increase in AMPA receptor‐mediated neurotransmission.