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Elucidating the Role of α3‐containing Nicotinic Acetylcholine Receptors (nAChRs) in Anxiety Behavior
Author(s) -
Smith Ciearra B.,
Tapper Andrew R.,
Gardner Paul D.
Publication year - 2018
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.2018.32.1_supplement.782.11
Subject(s) - nicotinic agonist , acetylcholine receptor , methyllycaconitine , anxiogenic , acetylcholine , cholinergic , elevated plus maze , nicotinic acetylcholine receptor , interpeduncular nucleus , neuroscience , gene knockdown , pharmacology , chemistry , microbiology and biotechnology , receptor , biology , psychology , biochemistry , anxiety , anxiolytic , psychiatry , central nervous system , apoptosis , midbrain
More than 260 million people suffer from anxiety disorder, thus it is important to understand the molecular mechanisms underlying anxiety disorder in order to develop more treatments. Studies showed that nicotinic acetylcholine receptors (nAChRs) play a role in anxiety‐related behaviors. nAChRs are ligand‐gated cation channels that bind the endogenous neurotransmitter acetylcholine for activation. There are eleven mammalian neuronal nAChR subunits, α2‐α7, α9, α10 and β2‐β4, which are encoded by the CHRNA2‐CHRNA7 , CHRNA9 , CHRNA10 , and CHRNB2‐B4 genes. These subunits co‐assemble to form functional homopentamers or heteropentamers consisting of various combinations of alpha and beta subunits. nAChRs are highly expressed in the habenulo‐interpeduncular pathway, a brain circuit that is involved with negative emotional state. Although knockout studies identified nAChRs as key players in anxiety‐related behaviors, little is known regarding the physiological relevance of α3‐containing nAChRs in anxiogenic behaviors due to α3 nAChR subunit knockout mice being inviable shortly after birth. I plan to test the physiological role of α3‐containing nAChRs in anxiety‐related behaviors by knocking down α3 nAChR subunits in the medial habenula (MHb) or interpeduncular nucleus (IPN) of 6‐week old mice and subsequently testing for anxiogenic behaviors. Here, I present approximately 45% and 80% knockdown of Chrna3 mRNA expression in Neuro‐2A (N2A) cells by lentiCRISPRv2‐sgRNA20 and shRNA 8843, respectively. Chrna3 mRNA levels were measured by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Thus, both CRISPR and shRNA approaches produced significant reduction of Chrna3 mRNA expression and can be applied in vivo to knockdown α3 nAChR subunit expression. My findings may identify α3‐containing nAChRs as novel targets for anxiety disorder therapies. Support or Funding Information NIH Award Number: DA035371 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .