title: Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal-prefrontal coherence.
abstract: Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T1R8, Canada. Electronic address: nathan.insel@utoronto.ca.
authors.forename: Nathan
authors.initials: N
authors.lastname: Insel
authors.affiliation: Department of Psychology, University of Toronto, Toronto, ON, Canada.
authors.forename: Maryna
authors.initials: M
authors.lastname: Pilkiw
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T1R8, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst St., Toronto, ON M5T 2S8, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Hutchison
authors.affiliation: Department of Psychology, University of Toronto, Toronto, ON, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
authors.forename: Kaori
authors.initials: K
authors.lastname: Takehara-Nishiuchi
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T1R8, Canada; Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst St., Toronto, ON M5T 2S8, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods; D003863:Depression / Q000503:physiopathology*; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D006179:Gyrus Cinguli / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley
keywords: Delta; Depression; Functional connectivity; Oscillations; Synchrony
references.citation: Am J Psychiatry. 1999 May;156(5):675-82
references.pmid: 10327898
references.citation: Hippocampus. 2005;15(7):867-73
references.pmid: 16149084
references.citation: Neuropsychopharmacology. 2012 Jun;37(7):1764-72
references.pmid: 22414813
references.citation: Front Integr Neurosci. 2010 Mar 10;4:2
references.pmid: 20431726
references.citation: Hippocampus. 2005;15(6):739-49
references.pmid: 16015622
references.citation: Brain Res. 1981 Jul 27;217(1):150-4
references.pmid: 7260612
references.citation: Biol Psychiatry. 2007 Sep 1;62(5):429-37
references.pmid: 17210143
references.citation: Brain Struct Funct. 2007 Sep;212(2):149-79
references.pmid: 17717690
references.citation: Neuron. 2005 Mar 3;45(5):651-60
references.pmid: 15748841
references.citation: PLoS Biol. 2005 Dec;3(12):e402
references.pmid: 16279838
references.citation: Brain Res. 1992 Jul 10;585(1-2):421-4
references.pmid: 1511330
references.citation: Psychol Med. 2014 Jul;44(10):2041-51
references.pmid: 24176176
references.citation: Science. 1993 Oct 29;262(5134):679-85
references.pmid: 8235588
references.citation: Neuron. 2010 Jun 24;66(6):921-36
references.pmid: 20620877
references.citation: Curr Opin Neurobiol. 2011 Jun;21(3):467-74
references.pmid: 21571522
references.citation: PLoS One. 2012;7(2):e32508
references.pmid: 22384265
references.citation: Neuroscience. 2002;114(2):475-92
references.pmid: 12204216
references.citation: Neuron. 2008 Nov 26;60(4):683-97
references.pmid: 19038224
references.citation: J Neurosci. 2009 Jul 29;29(30):9563-74
references.pmid: 19641119
references.citation: Hum Brain Mapp. 2007 Mar;28(3):247-61
references.pmid: 16779797
references.citation: Eur Neuropsychopharmacol. 2002 Dec;12 (6):527-44
references.pmid: 12468016
references.citation: Eur J Pharmacol. 2008 Feb 12;580(3):350-4
references.pmid: 18177637
references.citation: Brain. 2012 May;135(Pt 5):1498-507
references.pmid: 22418737
references.citation: J Neurosci. 2010 Dec 1;30(48):16314-23
references.pmid: 21123577
references.citation: J Neurosci. 2008 Jul 30;28(31):7837-46
references.pmid: 18667616
references.citation: J Neurophysiol. 2007 Sep;98 (3):1428-39
references.pmid: 17615124
references.citation: Neuron. 2005 Apr 7;46(1):141-51
references.pmid: 15820700
references.citation: Neurobiol Dis. 2014 Nov;71:205-14
references.pmid: 25131446
references.citation: Neuron. 2010 Jan 28;65(2):257-69
references.pmid: 20152131
references.citation: Am J Psychiatry. 2001 Jun;158(6):899-905
references.pmid: 11384897
references.citation: Cereb Cortex. 2009 Jan;19(1):24-40
references.pmid: 18453538
references.citation: Neuropsychopharmacology. 2014 Apr;39(5):1270-81
references.pmid: 24285211
references.citation: Soc Cogn Affect Neurosci. 2011 Oct;6(5):548-55
references.pmid: 20855296
references.citation: Biol Psychiatry. 2012 Jan 1;71(1):30-5
references.pmid: 22000731
references.citation: Brain Res. 1989 Dec 29;505(2):337-40
references.pmid: 2598054
references.citation: Exp Neurol. 1975 Oct;49(1 Pt 1):58-85
references.pmid: 1183532
references.citation: Hippocampus. 2000;10(4):438-46
references.pmid: 10985283
references.citation: Biol Psychiatry. 2010 Jan 15;67(2):117-24
references.pmid: 19819426
references.citation: Synapse. 1999 Jun 1;32(3):165-76
references.pmid: 10340627
references.citation: J Comp Neurol. 1991 Nov 22;313(4):574-86
references.pmid: 1783682
references.citation: Neuron. 2011 Oct 6;72(1):153-65
references.pmid: 21982376
references.citation: Front Psychiatry. 2012 Feb 28;3:14
references.pmid: 22403553
references.citation: PLoS Comput Biol. 2013;9(1):e1002853
references.pmid: 23300432
references.citation: Hippocampus. 2007;17 (10 ):957-76
references.pmid: 17598159
references.citation: Biol Psychiatry. 2008 Sep 15;64(6):461-7
references.pmid: 18639234