Exp Brain Res (1993) 93:1-5 Experimental BrainResearch 9 Springer-Verlag 1993 Disinhibition of hippocampal pyramidal cells during the transition into theta rhythm M. Stewart Department of Pharmacology, State University of New York Health Science Center, Brooklyn, NY 11203, USA Received: 14 July 1992 Accepted: 8 September 1992 Abstract. The activity of hippocampal complex-spike cells (presmned pyramidal cells) and theta cells (presumed interneurons) was examined during transi- tions from non-theta electroencephalogram (EEG) states to theta EEG states in freely moving and sleeping rats. Theta cell firing rates were significantly depressed in a 1-s period centered on the EEG transition relative to the surrounding 1-s periods (normalized rates+SEM): 1.05 4- 0.02 for the "non-theta" period, 0.59 4- 0.03 for the "transition" period, and 1.364-0.04 for the "theta" period (n = 26 cells). Conversely, complex-spike cell firing was significantly increased during the transition period: 0.51 4- 0.11 for the "non-theta" period, 2.244- 0.19 for the "transition" period, and 0.244-0.04 for the "theta" period (n = 27 cells). This diametrically altered activity indicates that theta cells must be actively inhibited during the transition. The increased activity in complex-spike cells during the transition may be simply a release from inhibitory control by interneurons. The pattern of theta cell inhibition together with increased complex-spike cell activity appears to be a general property of transitions into the theta EEG state, irrespective of behavior. It is suggested that increased activity in septal afferents (GA- BAergic cell activity greater than cholinergic cell activity) initially inhibits hippocampal interneurons. The inhibi- tion is not sustained because of an activity-dependent decrease in the potency of the septointerneuronal inhibi- tion, leaving the rhythmic excitatory (cholinergic) sep- tointerneuronal inputs, together with principal cell in- puts, to increase interneuron firing rates. Key words: Complex-spike cell - Theta cell Rhythmic slow activity - Rat Introduction Two broad classes of hippocampal neurons have been defined on the basis of their spontaneous and evoked firing patterns. Complex-spike cells fire single-action potentials or bursts of about two to ten action potentials of decreasing amplitude and increasing duration (Ranck 1973). Interspike intervals within the burst can be less than 5 ms. In Ammon's horn, these cells are considered to be pyramidal cells because of their location (Fox and Ranck 1975), their antidromic responses to fimbria/ fornix stimulation (Fox and Ranck 1981), and their firing properties (e.g., Nfifiez et al. 1987). Theta cells appear to be interneurons, located primarily in stratum oriens and stratum pyramidale of Ammon's horn and in the dentate hilus. This conclusion is based upon their location (Fox and Ranck 1975), their orthodromic responses to tim- bria/fornix or perforant path stimulation (Fox and Ranck 1981; Buzsaki and Eidelberg 1983), and the cor- respondence of their firing properties (action potential shape, discharge patterns) with identified interneurons or nonpyramidal cells in vitro (Schwartzkroin and Mathers 1978; Lacaille et al. 1987). Complex-spike cells and theta cells both fire in phase with the hippocampal theta rhythm (reviewed in Fox et al. 1986). It was noted in their original description (Ranck 1973) that theta cell firing rates were higher, by about a factor of 2, during theta rhythm than in non-theta electroencephalogram (EEG) states. Correspondingly, complex-spike cells were seen to fire at lower rates during hippocampal theta rhythm. This inverse relation of firing rates is consistent with theta cells inhibiting complex- spike cells. Complex-spike cells are least excitable on the phase of a theta cycle that theta cells fire (Rudell et al. 1980; Rudell and Fox 1984). It must be emphasized, however, that complex-spike cells can fire at very high rates when a rat is in a particular place in its environment (O'Keefe and Dostrovsky 1971; Muller et al. 1987). In fact, within a "place field", the firing rate of a complex- spike cell is higher (and its firing rate outside of the place field is lower) when theta rhythm is also present (Kubie et al. 1985). Only if the location-specific firing properties of complex-spike cells are excluded is the inverse relation of firing rates for complex-spike cells and theta cells apparent.