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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Deep Brain Stimulation* / methods
  • Depression / physiopathology*
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Depressive Disorder / therapy
  • Disease Models, Animal
  • Gyrus Cinguli / physiology
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Male
  • Nerve Net / metabolism
  • Nerve Net / physiopathology
  • Prefrontal Cortex / physiopathology*
  • Rats, Sprague-Dawley