Locus coeruleus bursts induced by glutamate trigger delayed perforant path spike amplitude potentiation in the dentate gyrus

Summary

Glutamate pressure ejections in the vicinity of locus coeruleus (LC) neurons have been shown to produce both short and long-lasting potentiation of perforant path (PP) evoked population spike amplitude in the dentate gyrus (DG). These effects of LC-glutamate activation resemble those produced by direct application of NE in vitro or in vivo. The present study monitored the cellular response of LC neurons to local glutamate ejections concomitant with stimulation of the PP evoked potential. Double barrel micropipettes or 33 ga cannulaelectrode assemblies permitted LC unit recording and glutamate ejection at or near the same site in urethane anesthetized rats. Glutamate ejections produced a burst of LC activity lasting 250–400 ms and followed by a depression of unit activity lasting 4.6 min. The maximal spike potentiation produced by LC activation was 158%. The first spike to exceed the control range occurred 34 s after the LC burst. Comparable silent intervals in LC unit activity induced by systemic clonidine were not accompanied by population spike amplitude potentiation. The mean duration of potentiation was 4.4 min except in four cases where responses remained potentiated for the duration of the experiment. The duration of potentiation was not correlated with the termination of LC depression. LC units recovered to baseline rates following glutamate induced depression of activity. The occurrence of potentiation appeared to require that glutamate activation reach a critical number of LC neurons since small glutamate ejections could produce a local burst without eliciting potentiation. Long-lasting changes were also related to larger glutamate volumes (100 nl). EPSP slope increases were briefer and occurred less frequently than spike amplitude changes suggesting EPSP-spike dissociation. The delay between the burst of LC activity and amplitude increases in the DG supports a model of NE action in which there are both rapid and slowly developing effects of NE release in the DG. In summary, brief, but intense, activation of LC neurons produces a delayed potentiation of DG responses lasting minutes to hours following the LC burst.