Mapping neuronal activation and the influence of adrenergic signaling during contextual memory retrieval

Abstract

We recently described a critical role for adrenergic signaling in the hippocampus during contextual and spatial memory retrieval. To determine which neurons are activated by contextual memory retrieval and its sequelae in the presence and absence of adrenergic signaling, transcriptional imaging for the immediate-early gene Arc was used in control and mutant mice lacking norepinephrine and epinephrine. This imaging approach permits the identification of neuronal genomic activation specific to one of two behavioral epochs in the same animal. Analysis revealed several brain regions that were more greatly activated by re-exposure to a salient versus neutral context 1 d after training in control mice (e.g., hippocampal CA3 and CA1, the amygdala, the dorsolateral caudate/putamen, the primary motor cortex, and parts of the rhinal cortices). In mice lacking norepinephrine and epinephrine, many of these regions exhibited significantly reduced activation (e.g., hippocampal CA1), while other regions did not (e.g., hippocampal CA3). In consideration with previous results, the current findings suggest a hypothesis in which adrenergic signaling may be critical for the transfer of retrieved contextual information from CA3 to CA1, where it would be compared to online sensory information coming directly from the cortex.