PROJECTIONS OF INTRINSIC CARDIAC NEURONS TO DIFFERENT TARGETS IN THE GUINEA-PIG HEART

We set out to determine the projections of the major immunohistochemic ally-defined populations of intrinsic cardiac neurons to different tar get tissues within the guinea-pig heart. Ultrastructural studies, and immunoreactivity to the neuronal marker, neuron-specific enolase, sugg ested that the number of axons of intrinsic neurons in most regions of the heart was low when compared with the populations of axons project ing from extrinsic sensory and sympathetic ganglia. Multiple-labelling immunofluorescence was used to demonstrate the terminals of the major populations of peptide-containing intrinsic neurons. The intrinsic na ture of peptide-containing axons was confirmed by long-term organotypi c culture of cardiac tissue, which resulted in degeneration of axons o f extrinsic neurons. The relative density and peptide content of intri nsic axons throughout the heart was not consistent with the relative p roportions of peptide-containing intracardiac nerve cell bodies observ ed previously. The most commonly-encountered axons contained immunorea ctivity (IR) to vasoactive intestinal peptide (VIP) alone, although ne rve cell bodies with VIP constituted less than 5% of the total populat ion of intrinsic neurons. Populations of axons containing IR to somato statin alone, somatostatin and substance P, neuropeptide Y (NPY) alone , somatostatin and NPY, or VIP and NPY, also were observed. Intrinsic axons containing substance P-IR were very rare, much more so than woul d be predicted from the peptide content of intrinsic nerve cell bodies . The regions of the heart with the most dense innervation by axons of intrinsic neurons were the cardiac valves, the atrio-ventricular node and the sino-atrial node, Each of these targets was innervated by sev eral populations of peptide-containing axons. Thus, each population of peptide-containing intrinsic neurons projected to a variety of target tissues within the heart. One possible interpretation of these result s is that immunohistochemically-distinct populations of intrinsic neur ons belong to different functional classes of neurons (sensory neurons , interneurons, final motor neurons), each of which innervates many re gions of the heart.