Noradrenergic axon terminals in the cerebral cortex of rat. III. Topometric ultrastructural analysis

Abstract

Summary Noradrenergic (NA) axons from the frontoparietal of an adult Sprague-Dawley rat were examined in 12 ribbons of 3 adjacent sections prepared for high resolution radioautography after specific labeling with [3H]NA in vivo. During electron microscopic examination of the various cortical layers, care was taken to determine the location of 30–49 reactive sectional profiles, which were identified as and found to correspond to 2556 different axonal parts. These were subsequently analyzed in terms of general configuration, organelle content, pattern of labeling and intracellular relationships. The NA arborization in cortex may be described as widely dispersed, unmyelinated axons of very fine caliber (ca. 0.35 μm), bearing small spherical enlargements (ca. 1 μm in diameter) and spaced at short intervals (1–3 μm). When viewed in single thin sections, these axonal varicosities always show aggregates of small, pleomorphic, agranular ‘synaptic’ vesicles, often accompanied by one or more large granular vesicles (LGVs) and mitochondria. Within intervaricose segments, microtubules and smooth endoplasmic reticulum are visible, as well as scattered LGVs and mitochondria. [3H]NA is highly concentrated inside the varicosities and to a lesser degree within intervaricose segments. It appears to be mainly associated with the small vesicles, some of the mitochondria, cisterns of smooth endoplasmic reticulum and LGVs. These preferential localizations probably reflect a strong binding capacity of the intra-axonal organelles toward endogenous norepinephrine. The figurative elements in cortical NA nerve endings are not sufficiently distinctive to be used as criteria for ultrastructural identification. Nevertheless, the examination of serial thin sections indicates that a small number of LGVs must be present in every NA varicosity. These data are compatible with a presumptive role of the LGVs in the transport of synthetic enzymes from the nerve cell bodies into the varicosities, wherein the storage of norepinephrine would be primarily ensured by the small vesicles. A very low proportion of cortical NA varicosities was found to be engaged in genuine synaptic relationships. Among 1835 reactive terminals, 341 of which were viewed in 2 or 3 adjacent sections, less than 5% exhibited typical junctional complexes, as opposed to 50% of unlabele boutons similarly sampled in the neighboring neuropil. The rare NA varicosities showing a synapse failed to reveal other structural differences with their congeners. Thus neither their intracortic repartition nor their cellular relationship support the existence of strategic contacts with restricted and/or specialized constituents of the parenchyma. It appears likely that in cortex endogenous norepinephrine may be liberated from all axonal varicosities where it is concentrated, and not only from the small number which form typical synapses. The fine structural characteristics of cortical NA fibers must therefore be considered in the light of recent demonstrations of their intricate and widespread distribution throughout the cerebral cortex, as well as distant, common origin in the locus coeruleus. In this context, it seems probable that the NA afferents might exert a diffuse, desynchronized and tonic influence on vast neuronal assemblies, and thus modulate integrative and/or specific cortical functions.