Biology, Animal Physiology

Available evidence suggests that the median raphe nucleus (MRN), when activated, produces a desynchronized hippocampal electroencephalog ram (EEG), and that this effect is sensitive to serotonergic (5-HT) manipulations. Experiment 1 examined the effect of injections into the MRN of agents that non-specifically (procaine) or selectively (8-OH-DPAT and buspirone) inhibit serotonin-containing MRN neurons. These substances produced hippocampal theta rhythm at short latencies and for long durations, suggesting that MRN 5-HT neurons are specifically responsible for controlling the hippocampal EEG. MRN 5-HT neurons are modulated by a facilitatory excitatory amino acid (EAA) input and an inhibitory influence from GABAergic interneurons within the MRN. Experiments 2 and 3 examined the effect of manipulations of these systems on the hippocampal EEG. Experiment 2 demonstrated that injections of the specific (AP-7) and non-specific (MK-801) NMDA antagonists, as well as the kainate/quisqualate antagonist (GAMS) into the MRN produce theta at short latencies and for long durations. Experiment 3 demonstrated that injections of the GABA$\sb{\rm A}$ agonist, muscimol, into the MRN produced hippocampal theta rhythm at short latencies and for long durations. In light of recent evidence suggesting a theta-pacemaker role for numerous brain nuclei, experiment 4 sought to re-examine the role of the medial septum/diagonal band complex (MS/DB) in hippocampal theta rhythm produced by injections of 8-OH-DPAT into the MRN. Four categories of MS/DB neurons were described: (1) cells which burst rhythmically with theta (rhythmical); (2) cells displaying a tonic increase in discharge with theta (theta-on); (3) cells displaying a dramatic decrease or cessation of discharge with theta (theta-off); and (4) cells which showed no changes in discharge in relation to theta (no-change). It was shown that injections of 8-OH-DPAT into the MRN caused a change in discharge of rhythmic MS/DB cells from an irregular non-bursting pattern during baseline conditions to a rhythmical, bursting pattern which was highly coherent with the hippocampal EEG.