The influences of increasing endogenous acetylcholine (eserine) and its blockade (scopolamine) on the effects of sensory stimuli were analyzed through the extracellular recording of the activity of individual hippocampal neurons of awake rabbits. An increase in the level of acetylcholine, accompanied by the appearance of stable theta rhythm, leads to a substantial decrease in the reactivity of neurons, the suppression, attenuation, and inversion of the majority of inhibitory reactions and of a substantial proportion of activational reactions including on-responses of a specific type. At the same time, a limited group of activational reactions is intensified and extended against the background of eserine. Scopolamine, which blocks theta rhythm, does not change or intensifies inhibitory and some activational reactions, including on-responses. Tonic reactions are shortened; however, their gradual extinction disappears. The effects described are preserved in the hippocampus in the presence of basal undercutting of the septum which eliminates ascending brainstem pathways. These data make it possible to draw the conclusion that, under normal conditions, a new (significant) sensory stimulus elicits in the hippocampus an initial stoppage (reset) of activity with the coordinated triggering of theta rhythm and the passage against this background of signals along the cortical input in a specific phase relationship to it. The period of theta modulation switched on by the signal fosters its recording and the limitation of the passage of subsequent, interfering signals. The septohippocampal influences may thus support the mechanism of selective attention, as a necessary precondition for memory.

Our previous studies on conscious rabbits showed that stimulation of the median cervical nucleus (MCN) decreases the extent and frequency of oscillatory theta activity in the septohippocampal system, while functional blockade of the nucleus by administration of the anesthetic lidocaine produces a stage high-frequency theta rhythm. The present study addresses the nature of the serotoninergic influences of the MCN (which also contains cells of other chemical natures) on the septohippocampal system. Experiments on conscious rabbits involved recording of the hippocampal EEG in control conditions and after microinjection of fluoxetine, a serotonin reuptake blocker which increases the levels of this transmitter in the brain. In all experiments, bilateral intracerebroventricular administration of fluoxetine hydrochloride (Sigma, St. Louis, MO; 15 microg in 5 microl of physiological saline) induced decreases in the magnitude of the hippocampal theta rhythm. In 15 of 18 (83.3%) of experiments, suppression of the oscillator activity by at least 50% of control was seen. The amplitude of the theta band in the spectral density histogram decreased by an average of 56 +/- 5.8% compared with control values (decreases in different experiments were from 7% to 90% of control p < 0.001). The latent period of these changes averaged 3.5 +/- 0.11 min (range: 2.9-4.1 min). The effect lasted 64.8 +/- 3.2 min (varying from 45.3 to 90 min in different experiments). There were no significant changes in the theta rhythm frequency, as compared with controls; this averaged 5.25 +/- 0.5 Hz (range: 4.5-6.5 Hz). The decrease in the magnitude of theta oscillations in the hippocampus after administration of fluoxetine provided evidence of the inhibitory control of rhythmic theta activity by the serotoninergic system of the brain.

EEG traces were recorded from the hippocampus and medial septal area of conscious guinea pigs in control conditions and on repeated stimulation of the perforant path. Changes in the correlations of activity in these structures during stimulation-evoked convulsions (a model of acute epilepsy) and during the process of epileptogenesis (a model of chronic epilepsy) were analyzed. A high correlation between baseline activity in the hippocampus and medial septal area seen in control conditions decreased sharply with the appearance of acute and chronic convulsions. Kindling led to hippocampus-independent generation of field convulsive discharges in the medial septal area. During kindling, there was a gradual disintegration of activity in the hippocampus and septum, which provides evidence for impairment of the operation of the septo-hippocampal network during epileptogenesis.

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