Release and Reuptake Sites for Norepinephrine Are Differently Distributed Across Layers of the Primary Visual Cortex in Macaque Monkeys.

Norepinephrine (NE) is released in cortex by axons arising from the locus coeruleus (LC). The cortical innervation patterns from LC have been mapped previously using antibodies directed against the vesicular synthetic enzyme for NE, dopamine β-hydroxylase (DBH), which provides information about putative release sites. We sought to quantify putative NE reuptake sites by immunolabeling the norepinephrine transporter (NET), focusing on the primary (V1) and secondary (V2) visual cortex of macaque monkeys. We used stereological methods to determine the density of axon segments immunoreactive for NET (NET+ segments) in V1 and V2, and non-stereological methods to compare the laminar distribution of NET+ segments and to compare the distribution of NET+ segments in V1 with segments immunoreactive for DBH (DBH+). We also developed a novel analysis approach on the basis of Bayesian statistics that allowed us to combine these quantitative data with qualitative data from previously published studies to generate and compare updated estimates of LC axon density. In line with prior reports based on DBH immunoreactivity, we find that LC axon density is higher in V2 than in V1 and has a similar laminar pattern across both areas. We also find that densities of DBH+ and NET+ segments differ across the layers of V1. This indicates that sites of NE release and reuptake may not be colocated and suggests a role for differing scales of diffusion in cortical modulatory effects mediated by NE.