Mechanisms regulating norepinephrine‐mediated α2‐IPSCs in the rat locus coeruleus

Abstract

Dopamine (DA) in the ventral tegmental area (VTA) and norepinephrine (NE) in the locus coeruleus (LC) provide feedback inhibition that allows these cells to auto‐regulate their excitability. Previously, we characterized DA D2‐receptor‐mediated inhibitory postsynaptic currents (D2‐IPSCs) in the VTA. Here, we characterized NE α2‐receptor‐mediated IPSCs (α2‐IPSCs) in the LC. Both D2 and α2 receptors activate potassium channels. Despite analogous signaling, the duration of the D2‐IPSC was about one‐fourth that of the α2‐IPSC (D2‐IPSC tau: 347 ms, n=8; α2‐IPSC tau: 1346 ms, n=17). To characterize transmission, we evoked IPSCs with varying‐intensity stimulations. In the VTA, increased stimulus intensity increased the amplitude, but not the time course, of the D2‐IPSCs (tau = 92 + 4%, n =12). In contrast, in the LC, increased stimulation intensity increased the amplitude and duration of the α2‐IPSCs (tau = 142 + 13%, n = 13). Increased stimulus intensity may evoke spillover of NE. To examine glutamate input, we applied the AMPA receptor antagonist DNQX. DNQX had no effect on the amplitude or duration of the D2‐IPSCs, but reduced the amplitude and duration of the α2‐IPSC (control tau: 1282 ms, DNQX tau: 660 ms, n=9). Thus, stimulation of the LC may drive glutamate release that potentiates NE release. These data indicate that different mechanisms may regulate catecholamine transmission. Support: DA026417.