Cortical interneurons: from Cajal to 2001.

After the collective work of many investigators, beginning with the early studies of Cajal, the following main [figure: see text] conclusions may be drawn regarding the morphology, biochemical characteristics and synaptic connections of interneurons: 1. Interneurons show a great variety of morphological, biochemical and physiological types. They constitute approximately 15-30% of the total population of neurons. 2. Because of the heterogeneity of interneurons and the lack of consensus as to which characteristics are essential for an individual neuron to be considered a member of a given cell type, there is no definitive classification of interneurons. Nevertheless, certain interneurons can be readily recognized by their unique morphological characteristics, or they can be more generally divided into subgroups on the basis of their biochemical characteristics, patterns of axonal arborization, or synaptic connections with pyramidal cells. 3. All interneurons have a more or less dense axonal arborization distributed near the cell body, mainly within the area occupied by their dendritic field. However, some interneurons may display, in addition, prominent long, horizontal or vertical axonal collaterals. [figure: see text] 4. Most interneurons form symmetrical synapses with both pyramidal cells and other interneurons, with the exception of chandelier cells, which only form synapses with the axon initial segment of pyramidal cells. Furthermore, interneurons are not only connected by chemical synapses (unidirectional connections), but they may also form electrical synapses through gap junctions (bidirectional) in a specific manner. 5. With the exception of chandelier cells, other types of interneurons include among their synaptic targets more than one type of postsynaptic element. But the degree of preference for these postsynaptic elements varies markedly between different types of interneurons. 6. The number of synapses made by a single axon originating from a given interneuron on another neuron is on the order of ten or less. Since, in general, cortical neurons receive many more interneuronal (symmetrical) synapses (on the order of a few hundred or thousand), a considerable convergence of various types of interneurons to pyramidal cells and interneurons appears to occur. 7. Most interneurons are GABAergic and also express a number of different neurotransmitters (or their synthesizing enzymes), neuropeptides and calcium-binding proteins. Thus, interneurons are, biochemically, widely heterogeneous. 8. Some of the morphologically identifiable neurons can be characterized by their particular biochemical characteristics, and some biochemically definable subgroups of interneurons display a particular morphology. However, different morphological types of GABAergic neurons may share one or several neurotransmitters, neuroactive substances and/or other molecular markers. Therefore, a great variety of subgroups of morphologically and biochemically identifiable neurons exist. 9. Some interneurons appear to be common to all species and, therefore, may be considered as basic elements of cortical circuits, whereas others may represent evolutionary specializations which are characteristic of particular mammalian subgroups and, thus, cannot be taken as essential, or general, features of cortical organization. 10. Given the complexity of cortical circuits and the areal and species differences, it is impossible to draw a "sufficiently" complete basic diagram of cortical microcircuitry that is valid for all cortical areas and species.