Sensory Responses of Neurons in the Medial Septal Area in Conditions of Modulation of Theta Activity Using the Alpha-2-Adrenoreceptor Agonist Clonidine

Abstract

Our previous studies on conscious rabbits showed that administration of the alpha-2-adrenoreceptor agonist clonidine induces dose-dependent changes in theta oscillations in the septohippocampal system. Low doses of clonidine suppressed theta activity, while high doses produced significant potentiation. It was suggested that the different effects of clonidine might be associated with differences in the sensitivities of pre- and postsynaptic alpha-2-adrenoreceptors to clonidine, this agent being a pure agonist of noradrenaline when used at high doses. It was suggested that functional synergism occurs between the activatory reticular formation and the noradrenergic system of the locus ceruleus in controlling the theta rhythm. The present study was performed to identify the nature of the responses of sensory neurons in the medial septal region in conditions of alterations in the magnitude of the theta rhythm induced by different doses of clonidine. Low and high doses of the agonist given bilaterally into the lateral ventricles were found to have different effects on the sensory responses of neurons in the medial septal region. Injection of small clonidine doses (0.5 microg in 5 microl into each lateral ventricle), which decrease theta activity, was found to lead to weakening of activatory processes and enhancement of inhibitory processes in the medial septal region. The number of activatory responses decreased significantly and persisting responses were significantly weakened; inhibitory responses, conversely, were seen more frequently and were significantly more marked. Administration of high clonidine doses (5 microg in 5 microl), which produce sharp increases in theta oscillations, led to significant reductions in the reactivity of cells in the medial septal region to sensory stimuli (from 76.8% in controls to 45% after clonidine), regardless of the nature of the initial responses. Persisting activatory and inhibitory responses were in most cases less marked than the initial responses. These results suggest that alpha-2-adrenoreceptors are involved in controlling the sensory reactivity of neurons in the medial septal region. The impairment of the normal processing of sensory stimuli seen during the continuous generation of rhythmic activity provoked by injection of large clonidine doses supports the role of the theta rhythm in the septohippocampal system as an active filter during the processing and recording of information.