Pacemaker neurons of the forebrain medical septal area and theta rhythm of the hippocampus.

The hippocampus is of critical importance for the organization of selective attention and memory. The activity of its neurons is rhythmically modulated by the direct afferent input from cholinergic and GABAergic neurons of the medial septal nucleus and the nucleus of diagonal band (MS-DB). This modulation is expressed in the hippocampal electroencephalogram as a slow (4-9 Hz) sinusoidal theta rhythm. The paper presents a short review of the authors' data on the properties of MS-DB cells, their interactions in organizing the theta expression in the hippocampus, and the probable functional significance of this rhythm. Extracellular recordings of neural activity of the MS-DB and hippocampus were performed in chronic alert rabbits with transection of various afferent pathways, in brain slices, and in the embryonic tissue grafts developing in the anterior eye chamber and brain. Theta modulation disappeared in all structures deprived of the MS-DB afferent connections, but was retained by MS-DB neurons under isolation conditions. A limited group of MS-DB neurons (6-8%) discharge in regular bursts after complete synaptic blockade in high Mg(2+)-low Ca2+ medium, while other neurons in these conditions exhibited the highly regular single-spike activity. Thus, the MS-DB neurons can be regarded as bursting and regular pacemakers. The frequency of bursts and the number of neurons involved in the rhythmic activity are in parallel increased by afferent stimulation-either natural (sensory stimuli) or imitated by electrical stimulation of ascending reticular formation. An increase in the number of MS-DB neurons secondarily involved in theta bursts with the resulting expression of theta rhythm in EEG can be also obtained by up-regulation of endogenous acetylcholine (by physostigmine), but in this case the frequency of theta is not changed. The MS-DB neurons contain acetylcholine and GABA as neurotransmitters. Analysis of the effects of their agonists and antagonists suggests that the frequency of theta depends on the GABAergic mechanism, while its power is controlled by cholinergic influences. In the control state, input signals triggered in the hippocampal neurons an inhibitory reset followed by synchronous theta modulation, gradually habituating during repeated presentations of the stimulus. Against the background of continuous theta evoked by physostigmine, the responses were blocked or significantly depressed, while after theta suppression by scopolamine the efficacy of the stimuli was increased, and habituation was absent. It is suggested that the theta rhythm operates as a selective filter: it augments and prolongs the input signal by which it was triggered and simultaneously protects it from the interference of extraneous stimuli appearing during its processing and registration. The theta rhythm may be regarded as an important mechanism of selective attention, which is a prerequisite for memory trace formation.