Noradrenaline induces IPSCs in rat medial septal/diagonal band neurons: involvement of septohippocampal GABAergic neurons

Abstract

1. The physiological and pharmacological actions of noradrenaline (NA) on neurons of the medial septum and diagonal band of Broca (MSDB) were examined using extracellular, intracellular and whole-cell patch-clamp recordings in an in vitro rat brain slice preparation. 2. In current- and voltage-clamp recordings with KCl- or potassium gluconate-containing electrodes, bath-applied NA increased the number of tetrodoxin- and bicuculline-sensitive synaptic events in > 80% of cholinergic- and GABA-type neurons tested. The NA-induced synaptic activity originated from GABAergic neurons located within the MSDB itself, as a similar effect occurred in brain slices in which the MSDB had been surgically isolated from neighbouring structures. 3. In antidromic studies, NA dose-dependently increased firing in a subpopulation of septohippocampal neurons with fast conducting fibres (mean conduction velocity, 1.78 +/- 0.10 m s-1; presumably GABAergic). The NA excitation was mimicked by the alpha 1-agonist phenylephrine (PE) and blocked by the alpha 1-antagonists prazosin and WB-4101, suggesting the presence of alpha 1-receptors on septohippocampal GABAergic neurons. 4. Similarly, in whole-cell recordings in both cholinergic- and non-cholinergic-type MSDB neurons, prazosin blocked the effects of NA and PE mimicked the effects of NA by inducing IPSCs with a similar amplitude distribution. 5. Consistent with the above findings, GABA-type neurons that responded directly to NA and PE with a prazosin-sensitive inward current were found within the MSDB. 6. In conclusion, NA, via alpha 1-adrenoceptors, excites MSDB septohippocampal GABAergic neurons and influences both septal and septohippocampal circuitry.