The long term objective of this research proposal is to understand at the electron microscopic level the synaptic organization of the cerebral cortex. Recent information available at the light microscopic level about the architectonic and connectional organization of the monkey auditory cortex can be elaborated on at the electron microscopic level in a propitious manner. These recent studies by us and others at the light microscopic level show that the association, thalamic and callosal cortical afferents terminate in specific cortical layers in disjunctive patterns that, in some cases, interdigitate. Also, in the superior temporal region of the monkey, a rostrocaudal and a mediolateral progression of cytoarchitectonic differentiation exists so that the more caudal portions are more highly differentiated than are the more rostral portions and the middle of the supratemporal plane is more highly differentiated than are the more medial and lateral portions. Furthermore, there is a highly organized connectional pattern between these rostrocaudal and mediolateral subdivisions. With a Golgi analysis, we have confirmed the presence of the cytoarchitectural specializations and defined the various neuronal cell types. With the Golgi-EM method combined with lesion-induced degeneration, we have successfully commenced the ultrastructural analysis of the callosal and thalamic synapses onto identified cells of the primary auditory cortex, and to date, have demonstrated thalamocortical contacts on several cell types, including spinous and nonspinous neurons. With the development of the horseradish peroxidase (HRP)-EM method, a projection site of the labeled cells, as well as their morphology, is known, thus providing more secure information about the identified cells than does the Golgi-EM method. We have completed a pilot study of this HRP-EM method and also developed a new anterograde lectin-EM axon marker. Thus, we propose to use both the Golgi-EM and HRP-EM methods combined with lesion-induced degeneration to determine the synaptic organizational patterns of the association, thalamic and callosal auditory connections. The spplication of these electron microscopic techniques in the monkey will allow insight into the synaptic organization of the functional components of a primary sensory system and aid in the interpretation of physiologic studies of the auditory system. We propose the use of the monkey in these studies since the principles of cerebral organization derived will be applicable, as much as is experimentally possible, to the human.