Contribution of synapses in the medial supramammillary nucleus to the frequency of hippocampal theta rhythm in freely moving rats.

We have previously shown that in urethane-anesthetized rats the frequency of rhythmical slow activity in the hippocampus ("theta") is controlled by the medial supramammillary nucleus (SuM). In particular, injections of procaine into SuM in urethane-anesthetized animals reduce the frequency of theta. However, it has been reported that, in freely moving animals, lesions of SuM do not affect theta. The present experiments were designed to resolve this anomaly. Injections of procaine or chlordiazepoxide into SuM in urethane-anesthetized animals reduced the frequency of theta elicited by reticular stimulation. Mapping showed that procaine injections in freely moving animals were effective in the same locations as under urethane anesthesia. Injections of chlordiazepoxide were effective in a more restricted area than procaine, consistent with an action on synapses in SuM and sparing fibers afferent to SuM. Analysis of the functional spread indicated an effective radius of diffusion of the drugs of 500 microns. With optimal placements, this implied an action on at least 80% of SuM. However, in contrast to the results under urethane, the maximal frequency reductions obtained were less than 50% of the theoretical maximum. In a number of animals receiving repeated injections into SuM, lesions developed which encompassed the whole of SuM. As previously reported, theta was largely intact in SuM-lesioned animals. However, the frequency of theta produced by reticular stimulation was reduced after lesion by approximately the same amount as by procaine injections before lesion. These results suggest that in freely moving animals SuM is only one of two or more nuclei which jointly control the frequency of reticular-elicited theta.