Median raphe stimulation disrupts hippocampal theta via rapid inhibition and state-dependent phase reset of theta-related neural circuitry

J Neurophysiol. 2008 Jun;99(6):3009-26. doi: 10.1152/jn.00065.2008. Epub 2008 Apr 24.


Evidence has accumulated suggesting that the median raphe (MR) mediates hippocampal theta desynchronization. However, few studies have evaluated theta-related neural circuitry during MR manipulation. In urethane-anesthetized rats, we investigated the effects of MR stimulation on hippocampal field and cell activity using high-frequency (100 Hz), theta burst (TBS), and slow-frequency electrical stimulation (0.5 Hz). We demonstrated that high-frequency stimulation of the MR did not elicit deactivated patterns in the forebrain, but rather elicited low-voltage activity in the neocortex and small-amplitude irregular activity (SIA) in the hippocampus. Both hippocampal phasic theta-on and -off cells were inhibited by high-frequency MR stimulation, although MR stimulation failed to affect cells that had neither state or phase relationships with theta field activity. TBS of the MR-induced theta field activity phase locked to the stimulation. Slow-frequency stimulation elicited a state-dependent reset of theta phase through a short-latency inhibition (5 ms) in phasic theta-on cells. Subpopulations of phasic theta-on cells responded in either oscillatory or nonoscillatory patterns to MR pulses, depending on their intraburst interval. off cells exhibited a state-dependent modulation of cell firing occurring preferentially during nontheta. The magnitude of MR-induced reset varied as a function of the phase of the theta oscillation when the pulse was administered. Therefore high-frequency stimulation of the MR appears to disrupt hippocampal theta through a state-dependent, short-latency inhibition of rhythmic cell populations in the hippocampus functioning to switch theta oscillations to an activated SIA field state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Radiation
  • Electric Stimulation*
  • Fourier Analysis
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Male
  • Neocortex / physiology
  • Nerve Net / physiology*
  • Nerve Net / radiation effects
  • Neural Inhibition / physiology*
  • Neural Inhibition / radiation effects
  • Neurons / classification
  • Neurons / physiology
  • Neurons / radiation effects
  • Raphe Nuclei / physiology
  • Raphe Nuclei / radiation effects*
  • Rats
  • Rats, Long-Evans
  • Theta Rhythm*