Neuronal and Synaptic Organization of Layer 1 in the Human Temporal Lobe Neocortex: A Quantitative Electron Microscopic Analysis

Abstract

The mammalian brain consists of anatomically and functionally defined individual microcircuits and networks formed by neurons and their synapses. Synapses are the structural key element, not only connecting various neuronal cell types in different brain regions, nuclei or layers, for example in the cortical column, but more important are involved in the execution, modulation and termination of signal transduction between neurons. Hence synapses represent a major driving force in all cognitive processes of the human brain. Since the announcement of the ‘decade of the brain’ nearly 20 years ago enormous efforts were made in the description of structural and functional characteristics of synapses in various brain regions and animals species using high-end electrophysiological, light- and electron microscopic and molecular techniques. However, our knowledge about the structural composition, in particular the synaptic organization of the human brain, is still comparably small. This can partially be attributed to the availability of human brain tissue for such sophisticated experiments. However, using access tissue from biopsy samples from pharmacoresistant epileptic patients enabled us to perform a quantitative analysis of synaptic boutons in Layer 1 of the human temporal lobe neocortex. Serial ultrathin sections provided the basis for fine-scale electron microscopy and subsequent software supported 3D volume reconstruction of synaptic structures and finally, the generation of quantitative 3D models of synapses in Layer 1. Such models can then be used for direct comparison with other central nervous system synapses where quantitative data are available or for numerical simulations of various synaptic parameters not accessible to experiment in the human brain. Finally, this master thesis will contribute to the detailed description of the neuronal and synaptic organization of the human brain at the cellular, subcellular and molecular level of the human neocortex as exemplified for the temporal lobe neocortex that will be made accessible by our group. In contrast to the underlying cortical layer, Layer 1 in the adult human brain is comparably cell sparse, but contained so-called Cajal-Retzius cells and GABAergic interneurons, as well as dendritic and synaptic structural elements and non-neuronal astrocytes and oligodendrocytes. Upon structural criteria Layer 1 can be subdivided into Layer 1a (astrocytic and cellular domain) and Layer 1b a more ‘synaptic and dendritic domain’. The majority of synaptic contacts were excitatory in nature and established on dendritic spines. Synaptic boutons varied substantially in surface area and volume, in the content of mitochondria and the total synaptic vesicle pool per bouton. Most synaptic terminals (70%) had a single neurotransmitter release site (active zone). The comparably large total pool of synaptic vesicles suggests also relatively large RRPs, RPs and resting pools. In summary, our results demonstrate similarities but also distinct differences not only with synapses in other layers of the human temporal lobe neocortex but also with their counterparts in various animal species. Hence our findings will contribute to a fundamental and improved understanding of the ‘behavior’ of synapses embedded in cortical networks of the normal and pathologically altered brain.