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Exp Neurol. 2015 Jul;269:1-7. doi: 10.1016/j.expneurol.2015.03.023. Epub 2015 Apr 1.

Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal-prefrontal coherence.

Author information

1
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T1R8, Canada. Electronic address: nathan.insel@utoronto.ca.
2
Department of Psychology, University of Toronto, Toronto, ON, Canada.
3
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T1R8, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
4
Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst St., Toronto, ON M5T 2S8, Canada.
5
Department of Psychology, University of Toronto, Toronto, ON, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
6
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.

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.

KEYWORDS:

Delta; Depression; Functional connectivity; Oscillations; Synchrony

PMID:
25842268
PMCID:
PMC5633366
DOI:
10.1016/j.expneurol.2015.03.023
[Indexed for MEDLINE]
Free PMC Article

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