title: CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala.
abstract: Hyperactivation of the amygdala is implicated in anxiety and mood disorders, but the precise underlying mechanisms are unclear. We previously reported that depletion of serotonin (5-hydroxytryptamine, 5-HT) in the basolateral nucleus of the amygdala (BLA) using the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) potentiated learned fear and increased glutamate receptor (Glu) expression in BLA. Here we investigated the hypothesis that CaMKII facilitates anxiety-like behavior and increased Glu/AMPA receptor subunit A1 (GluA1) expression following depletion of 5-HT in the BLA. Infusion of 5,7-DHT into the BLA resulted in anxiety-like behavior in the open field test (OFT) and increased the phosphorylation of CaMKIIα (Thr-286) in the BLA. Knockdown of the CaMKIIα subunit using adeno-associated virus (AAV)-delivered shRNAi concomitantly attenuated anxiety-like behavior in the OFT and decreased GluA1 expression in the BLA. Our results suggest that the CaMKII signaling plays a key role in low 5-HT-induced anxiety and mood disturbances, potentially through regulation of GluA1 expression in the BLA.
authors.affiliation: Institute for Biomedical Studies, Baylor University, Waco, TX, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Tran
authors.affiliation: Institute for Biomedical Studies, Baylor University, Waco, TX, USA; Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA. Electronic address: NB_Keele@baylor.edu.
authors.forename: N Bradley
authors.initials: NB
authors.lastname: Keele
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage; D015854:Up-Regulation
chemical_list: D015116:5,7-Dihydroxytryptamine; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D018091:Receptors, AMPA; D012701:Serotonin; D018490:Serotonin Agents
keywords: 5-HT; AAV; CaMKII; Glutamate; Immunoblot; RNAi; RT-PCR; amygdala
references.citation: Neural Plast. 2012;2012:405926
references.pmid: 22830051
references.citation: J Biol Chem. 2012 Mar 9;287(11):8495-506
references.pmid: 22253441
references.citation: Cell Mol Neurobiol. 2013 Jul;33(5):723-9
references.pmid: 23657616
references.citation: Transl Psychiatry. 2013;3:e298
references.pmid: 24002084
references.citation: J Appl Physiol (1985). 2000 May;88(5):1898-906
references.pmid: 10797155
references.citation: J Biol Chem. 2001 Jul 13;276(28):25929-38
references.pmid: 11340067
references.citation: Trends Neurosci. 2001 Dec;24(12):713-9
references.pmid: 11718876
references.citation: Science. 2002 Oct 25;298(5594):776-80
references.pmid: 12399578
references.citation: J Biol Chem. 2004 Mar 26;279(13):12484-94
references.pmid: 14722083
references.citation: J Neurosci. 2004 Mar 31;24(13):3281-8
references.pmid: 15056707
references.citation: Int J Neuropsychopharmacol. 2004 Sep;7(3):243-8
references.pmid: 15154976
references.citation: Annu Rev Neurosci. 1992;15:353-75
references.pmid: 1575447
references.citation: Science. 1992 Jul 10;257(5067):201-6
references.pmid: 1378648
references.citation: Arch Gen Psychiatry. 1994 Jan;51(1):34-8
references.pmid: 7506517
references.citation: J Clin Psychiatry. 1996;57 Suppl 6:5-10
references.pmid: 8647798
references.citation: Brain. 1997 Nov;120 ( Pt 11):1937-59
references.pmid: 9397013
references.citation: J Neuropathol Exp Neurol. 1998 Nov;57(11):1078-88
references.pmid: 9825945
references.citation: J Neurophysiol. 1999 Jul;82(1):69-85
references.pmid: 10400936
references.citation: Mol Ther. 2005 Jun;11(6):899-905
references.pmid: 15922960
references.citation: Trends Neurosci. 2005 Aug;28(8):436-45
references.pmid: 15982754
references.citation: Biochem Soc Trans. 2005 Dec;33(Pt 6):1354-6
references.pmid: 16246117
references.citation: Epilepsy Behav. 2005 Nov;7(3):325-35
references.pmid: 16103019
references.citation: J Neurophysiol. 2006 Apr;95(4):2143-54
references.pmid: 16381802
references.citation: Mol Biol Cell. 2007 Dec;18(12):5024-33
references.pmid: 17942605
references.citation: J Neurosci. 2008 Jun 11;28(24):6250-7
references.pmid: 18550767
references.citation: Mol Brain. 2009;2:6
references.pmid: 19257910
references.citation: J Neurosci Res. 2009 Jun;87(8):1823-31
references.pmid: 19224582
references.citation: PLoS One. 2011;6(4):e18739
references.pmid: 21494567
references.citation: Neuroreport. 2011 Oct 26;22(15):758-61
references.pmid: 21876464
references.citation: Int J Neuropsychopharmacol. 2013 May;16(4):919-24
references.pmid: 23360771