Abstract
Activation of locus coeruleus (LC) neurons is typically followed by inhibition of impulse activity lasting hundreds of ms. Previous studies have implicated two possible mechanisms for this postactivation inhibition: (1) collateral synaptic interactions among LC neurons; and (2) spike-induced, calcium-activated potassium conductance in the soma-dendritic membrane of LC cells. In the present study, antidromic or sensory stimuli were presented at near-threshold intensities for activation of LC neurons. A special computer program accumulated activity for trials yielding driven responses separately from that for trials of identical stimuli during the same train that failed to evoke activity. We found significant inhibition of LC impulse activity for antidromic or sensory stimuli that failed to excite the recorded cell as well as for stimuli that activated the recorded cell. The former result precludes an essential role of intrinsic inhibitory membrane currents (e.g. calcium-activated potassium conductance) in generating postactivation inhibition. Administration of the α antagonist piperoxane reduced the magnitude of inhibition on both driven and non-driven trials. Our findings indicate that inhibition on non-driven trials appears to be a synaptically, mediated phenomenon, perhaps reflecting norepinephrine released from neighboring LC neurons that are activated. Furthermore, our data support the presence of a spike-dependent mechanism that also contributes substantially to postactivation inhibition in these cells. Thus, the overall results indicate the presence of two intracoerulear mechanisms that mediate postactivation inhibition characteristic of noradrenergic LC neurons.