Locus coeruleus activation by physiological challenges

Abstract

Studies were designed to elucidate the neurotransmitter(s) and circuitry involved in activation of noradrenergic locus coeruleus (LC) neurons by different physiological challenges in halothane-anesthetized rats, and to understand the functional consequences of LC activation by these stimuli. LC spontaneous discharge rate was increased by a hypotensive challenge and by bladder distention. The effect produced by hypotension, but not by bladder distention, was prevented by antagonists of the stress-related neurohormone, corticotropin-releasing factor (CRF), administered ICV or directly into the LC. In contrast, ICV administration of excitatory amino acid antagonists prevented LC activation by bladder distention, but not by hypotension. These results suggest that LC activation by hypotension and bladder distention requires separate neurotransmitter systems, with CRF mediating activation by hypotension and excitatory amino acids mediating activation by bladder distention. Both physiological challenges activated forebrain electroencephalographic (EEG) activity, as indicated by a shift from low frequency, high amplitude activity to high frequency, low amplitude activity recorded from the frontal cortex. The EEG effects appeared to be temporally correlated with LC activation. Bilateral LC inactivation or microinfusion of CRF antagonists into the LC prevented both LC and EEG activation by hypotension. These results suggest that one consequence of LC activation during stress or physiological challenges may be to increase or maintain arousal.