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Optogenetic and pharmacologic dissection of G‐protein and arrestin dependent signaling mechanisms of β2 adrenergic receptors (662.3)
Author(s) -
Siuda Edward,
Bruchas Michael
Publication year - 2014
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/fasebj.28.1_supplement.662.3
Subject(s) - optogenetics , g protein coupled receptor , arrestin , signal transduction , neuroscience , receptor , functional selectivity , microbiology and biotechnology , g protein , biology , intracellular , chemistry , biochemistry
β‐adrenergic receptors (βARs) are GPCRs that signal in a canonical Gαs‐mediated fashion. It is also clear that βARs signal independently of G‐proteins in a manner referred to as functional selectivity. While βARs activate downstream effectors through G‐protein‐dependent and independent mechanisms, it is unclear whether βAR functional selectivity occurs in the CNS in endogenous systems, and what role this plays in behavior. Here we report that recruitment of noradrenergic inputs and activation of β2‐adrenergic signaling in the basolateral amygdala (BLA) induces anxiety‐like behavior in mice. However, it is unclear how signaling to G‐proteins, or arrestin alters downstream behavioral phenotypes within the BLA complex in affective behaviors. To elucidate the roles of G‐protein and arrestin dependent intracellular signaling we first developed novel “functionally selective” optically sensitive GPCRs. We then used pharmacological methods and in vitro optogenetic techniques to characterize the temporal kinetics of cAMP and MAPK activity. Finally, we combined behavioral pharmacology and in vivo optogenetic techniques to express cell‐type‐specific, optically sensitive, wild type and functionally selective mutants to examine the effects of G‐protein and arrestin dependent signaling on anxiety behavior. Together, these tools and findings have use in dissecting neural circuits in anxiety, and the role of biased GPCR signaling in vivo. Grant Funding Source : Supported by R21‐DA035144, EUREKA Grant R01‐DA037152, TR01‐NS081707‐01; NIDA (MRB)