Differential effects of norepinephrine on hippocampal complex-spike and θ-neurons

Abstract

The central noradrenergic system has long been postulated to modulate learning and memory. A brain structure known to be important in these functions is the hippocampus. Since the hippocampus receives a noradrenergic projection from the locus coeruleus, knowledge of norepinephrine's actions in the hippocampus may help determine its role in learning and memory. In the present study, the effects of norepinephrine were examined on two hippocampal cell types: complex-spike and θ-neurons. In the hippocampus, there is good evidence that complex-spike cells are pyramidal neurons, while θ-neurons are interneurons. Extracellular action potentials from hippocampal neurons were recorded using multibarrel glass micropipettes. Drugs were locally applied using pressure micro-ejection. Norepinephrine inhibited the spontaneous firing of complex-spike cells, while θ-neurons were excited. The inhibitory response of complex-spike neurons was mediated by an α 1-receptor. However, selective agonists for the α 2- and β-noradrenergic receptors excited the complex-spike cells. The noradrenergic-induced excitatory response of θ-neurons was also mediated by α 2 and β-receptors. This study provides evidence that locally applied norepinephrine produces different responses on two types of hippocampal neurons. Furthermore, these differential responses arise primarily from the activation of distinct populations of noradrenergic receptors.