Quantified regional and laminar distribution of the noradrenaline innervation in the anterior half of the adult rat cerebral cortex

Abstract

The regional and laminar distribution of the noradrenaline (NA) innervation in the adult rat cerebral cortex was quantified in radioautographs of semithin sections from whole hemisphere slices incubated with tritiated catecholamines and a monoamine oxidase inhibitor. Uptake‐labeled axonal varicosities (aggregates of silver grains) were counted with the help of a computerized image analyzer in seven cytoarchitectonic areas of the rostral half of the cortex: Cg3, rostral AID, Cg2, Fr1, Par1, caudal AID, and Pir (prepiriform) according to Zilles's nomenclature. Both dopamine (DA) and NA terminals were detected after incubation with [³H]DA and citalopram or with [³H]NA alone. In the presence of desipramine (DMI), DA terminals alone were demonstrated; the number of NA terminals was then obtained by subtraction from counts in adjacent slices incubated with or without DMI. These counts suggested that DA and NA varicosities were fully visualized only after labeling with their respective tritiated amine. Similar numbers of labeled NA varicosities as inferred after [³H]NA incubation with or without DMI were observed after [³H]NA incubation in the presence of benztropine (BZ). This indicated that NA terminals were then maximally detected to the exclusion of the DA ones, and the latter approach was adopted for the acquisition of normative data. Since the average diameter of the labeled NA varicosities was known from earlier measurements in electron microscope radioautographs, the initial counts of labeled sites/mm² of histological section could be expressed as numbers of varicosities/mm³ of tissue following a double correction for incomplete detection at the chosen duration of radioautographic exposure and section thickness. The overall density of NA innervation was thus estimated at 1.2 million varicosities/mm³ of tissue, with no statistically significant differences between the seven cortical areas examined. In every region, the number of NA terminals was the greatest in the molecular layer (1.5–2 times the density in the rest of cortex) and then progressively decreased in the underlying cortex, with a two‐ to threefold difference between upper and lower layers. These numerical data allowed an estimation to be made of the possible number of cortical NA varicosities per locus coeruleus nerve cell body of origin (at least 300,000), of their average number per cortical neuron (30–50), their actual incidence among all terminals in the cortex (1/1,000), their mean endogenous amine content per varicosity (0.22 fg), and the mean number of recognition sites for the uptake blocker DMI (4,500/varicosity). Further quantification of the cortical NA innervation in correlation with these and other measurable parameters of Na function under physiological or experimentally altered conditions should improve our understanding of the properties and role(s) of this monoamine in cerebral cortex.