Quantitative three-dimensional analysis of the catecholaminergic innervation of identified neurons in the macaque prefrontal cortex.

The present study provides a complete quantitative three-dimensional analysis of neurons in primate prefrontal cortex targeted by catecholaminergic axons. Individual pyramidal and nonpyramidal cells in fixed slices were filled with Lucifer yellow (LY) and recovered with anti-LY antibody combined with anti-tyrosine hydroxylase (TH) antisera to reveal catecholaminergic axons. The total number of TH contacts and TH apposition density (THAD) was obtained for pyramidal and nonpyramidal cells in different layers. Four TH contacts (two on spines and two on shafts) were selected for correlated electron microscopic examination and serially sectioned; all four were confirmed as membrane appositions. Quantitative analysis revealed 90 TH contacts per pyramidal neuron in layer III, with a density of 0.8 per 100 microm of dendritic length (i.e., averaging one contact per basal dendrite). Remarkably, pyramids of layers III, V, and VI had the same THAD values, with a highly regular distribution of TH terminals on their spiny dendritic trees. In contrast, TH contacts on nonpyramidal neurons in layer III were half as dense and, moreover, were distributed irregularly and showed large variation from cell to cell. Neurons in layers II and superficial III had the highest THAD, as compared with deeper layers (1.4 vs 0.7 per 100 micron of dendritic length for pyramids; 0.53 vs 0.4 for interneurons). The highly organized TH innervation of pyramidal neurons, with at least one contact on virtually every dendrite, indicates that catecholaminergic, presumably dopaminergic, terminals are placed strategically along the entire dendritic tree to modulate most, if not all, of the excitatory input of a neuron. At the same time, the sparsity of contacts per dendrite may explain cortical vulnerability in diseases involving dopamine.