Median raphe stimulation disrupts hippocampal theta via rapid inhibition and state-dependent phase reset of theta-related neural circuitry.
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.
Jackson
Jesse
J
Behavioral Neuroscience Research Group, Department of Psychology, The University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
Dickson
Clayton T
CT
Bland
Brian H
BH
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005583:Fourier Analysis; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D019579:Neocortex / Q000502:physiology; D009415:Nerve Net / Q000502:physiology* / Q000528:radiation effects; D009433:Neural Inhibition / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000502:physiology / Q000528:radiation effects; D011903:Raphe Nuclei / Q000502:physiology / Q000528:radiation effects*; D051381:Rats; D020318:Rats, Long-Evans; D013826:Theta Rhythm