Median Raphe Stimulation Disrupts Hippocampal Theta Via Rapid Inhibition and State-Dependent Phase Reset of Theta-Related Neural Circuitry

• Published in: Journal of neurophysiology 2008-06, Vol.99 (6), p.3009-3026
• Main Authors: Jackson, Jesse, Dickson, Clayton T, Bland, Brian H
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00065.2008

1 Behavioral Neuroscience Research Group, Department of Psychology, and 2 Hotchkiss Brain Institute, The University of Calgary, Calgary; and 3 Departments of Psychology, Physiology, and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada Submitted 18 January 2008; accepted in final form 17 April 2008 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. Address for reprint requests and other correspondence: B. H. Bland, Department of Psychology, Behavioral Neuroscience Research Group, The University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4 (E-mail: bhbland{at}ucalgary.ca )