Locus Coeruleus Phasic, But Not Tonic, Activation Initiates Global Remapping in a Familiar Environment

Locus coeruleus (LC) neurons, the source of hippocampal norepinephrine (NE), are activated by novelty and changes in environmental contingencies. Based on the role of monoamines in reconfiguring invertebrate networks, and data from mammalian systems, a network reset hypothesis for the effects of LC activation has been proposed. We used the cellular compartmental analysis of temporal FISH technique based on the cellular distribution of immediate early genes to examine the effect of LC activation and inactivation, on regional hippocampal maps in male rats, when LC activity was manipulated just before placement in a second familiar (A/A) and/or novel environment (A/B). We found that bilateral phasic, but not tonic, activation of LC reset hippocampal maps in the A/A condition, whereas silencing the LC with clonidine before placement in the A/B condition blocked map reset and a familiar map emerged in the dentate gyrus, proximal and distal CA1, and CA3c. However, CA3a and CA3b encoded the novel environment. These results support a role for phasic LC responses in generating novel hippocampal sequences during memory encoding and, potentially, memory updating. The silencing experiments suggest that novel environments may not be recognized as different by dentate gyrus and CA1 without LC input. The functional distinction between phasic and tonic LC activity argues that these parameters are critical for determining network changes. These data are consistent with the hippocampus activating internal network representations to encode novel experiential episodes and suggest LC input is critical for this role.