GABAergic agents in the medial septal nucleus affect hippocampal theta rhythm and acetylcholine utilization

Neurons of the medial septal nucleus are important in regulating the physiological activity of the hippocampus. If intraseptal injection of putative neurotransmitter substances affects the turnover rate of hippocampal acetylcholine, then concomitant changes would be expected in the electrophysiologic activity of the hippocampus. A GABA agonist, muscimol, was injected into the medial septum of rats and the effects on hippocampal electrical activity and acetylcholine utilization were studied. The intraseptally injected muscimol (100 ng) resulted in hippocampal electrographic records containing low amplitude asynchronous waves and significantly less rhythmic slow activity (RSA, 6-9 Hz), compared to control injections of saline. This effect was antagonized by prior intraseptal injection of bicuculline (3 micrograms). The hippocampal electrical activity returned to normal within 100 min. The utilization of acetylcholine was significantly reduced by intraseptal muscimol at times after administration when electrographic activity was also altered, and spontaneous behavioral movement was increased. These results suggest a physiological connection between hippocampal RSA generation and GABAergic mechanisms in the septum.