Neuronal and synaptic organization of the centromedian nucleus of the monkey thalamus: a quantitative ultrastructural study, with tract tracing and immunohistochemical observations

Summary The ultrastructure of the centromedian nucleus of the monkey thalamus was analysed qualitatively and quantitatively and projection neurons, local circuit neurons, and synaptic bouton populations identified. Projection neurons were mostly medium-sized, with oval-fusiform or polygonal perikarya, few primary dendrites, and frequent somatic spines; local circuit neurons were smaller. Four basic types of synaptic boutons were distinguished: (1) Small- to medium-sized boutons containing round vesicles (SR) and forming asymmetric contacts, identified as corticothalamic terminals. (2) Heterogeneous medium-sized boutons with asymmetric contacts and round vesicles, similar to the so-called large round (LR) boutons, which were in part of cortical origin. (3) Heterogeneous GAD-positive small- to medium-sized boutons, containing pleomorphic vesicles and forming symmetric contacts (F1 type), which included pallidothalamic terminals. (4) Presynaptic profiles represented by GAD-positive vesicle-containing dendrites of local circuit neurons. Complex synaptic arrangements, serial synapses and triads with LR and SR boutons engaging all parts of projection neuron dendrites and somata, were seen consistently, whereas classical glomeruli were infrequent. LR and SR boutons also established synapses on dendrites of local circuit neurons. F1 boutons established synapses on projection neuron somata, dendrites and initial axon segments. Compared to other previously studied motor-related thalamic nuclei, differences in synaptic coverage between proximal and distal projection neuron dendrites were less pronounced, and the density of synapses formed by local circuit dendrites on projection neuron dendrites was lower. Thus, compared to other thalamic nuclei, the overlap of different inputs was higher on monkey centromedian cells, and centromedian inhibitory circuits displayed a different organization.     

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. II. Terminations upon neuronal perikarya and dendritic shafts

Summary The forms of dendrites in layer IV receiving degenerating thalamocortical axon terminals directly on their shafts were examined in serial thin sections. Reconstructions showed these dendrites varied in thickness between 2.5 and 0.5 m. They had essentially smooth contours and rarely showed evidence of protrusions or spines. They were further characterized by the presence of many synapses along their shafts. Only about one in 12 of these synapses was formed by degenerating thalamocortical axon terminals.These smooth dendrites emerged from neuronal perikarya that also received degenerating axon terminals which formed asymmetric synaptic junctions. Such cell bodies bore both symmetric and asymmetric synaptic junctions, and not all of the latter were caused to degenerate after a thalamic lesion. These postsynaptic neurons appeared to be of two kinds, ones with thin dendrites that often contained closely packed microtubules, and others with thicker dendrites that emerged from the poles of oval perikarya.     

Aspinous and sparsely-spinous stellate neurons in the visual cortex of rats contain glutamic acid decarboxylase

Summary Glutamic acid decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter -aminobutyric acid (GABA), has been localized in the rat visual cortex by immunocytochemical methods with both light and electron microscopy. In both colchicine-injected and non-injected preparations of the visual cortex, GAD-positive reaction product was observed in somata, proximal dendrites and axon terminals of non-pyramidal neurons. The GAD-positive terminals were observed to form symmetric synaptic junctions most commonly with dendritic shafts and somata of pyramidal and stellate neurons and less frequently with initial axon segments of pyramidal neurons and dendritic spines. In colchicine-injected preparations, GAD-positive somata were located in all cortical layers including the immediately subjacent white matter. In contrast, sections from non-injected rats displayed GAD-positive somata within a superficial and a deep cortical band. The GAD-positive somata observed in both types of preparations received both symmetric and asymmetric synaptic junctions, lacked apical dendrites, and had radially oriented dendrites of small diameter. These characteristics of GAD-positive neurons indicate that they are aspinous and sparsely-spinous stellate neurons. The localization of GAD within these neurons in combination with physiological and pharmacological data indicate that these local circuit neurons mediate GABA-ergic inhibition in the neocortex.     

The termination of thalamo-cortical fibres in the visual cortex of the cat

Summary An electron microscopic study has been made of the site and mode of termination of thalamo-cortical fibres in area 17 of the visual cortex of the cat. Thalamo-cortical fibres had been selectively interrupted 4–5 days before perfusion of the brain. In agreement with previous studies, degenerating axon terminals were found in layer I, in the deep part of layer III, and in layer IV of the cortex. In addition, a few degenerating thalamo-cortical axon terminals were found making synapses upon spines and small dendrites in layer VI. Two examples were seen of degenerating axon terminals making axo-dendritic synapses upon dendrites in continuity with their cell bodies. These neurons were not large stellate cells and were probably pyramidal.     

The termination of callosal fibres in the auditory cortex of the rat. A combined Golgi--electron microscope and degeneration study

When the corpus callosum of the rat is sectioned, the callosal fibres in the cerebral cortex undergo degeneration. In the auditory cortex (area 41) the degenerating axon terminals form asymmetric synapses, and the vast majority of them synapse with dendritic spines. Some other synapse with the shafts of both spiny and smooth dendrites, and a few with the perikarya of non-pyramidal cells. The degenerating axon terminals are contained principally within layer II/III, in which they aggregate in patches. Using a technique in which neurons within the cortex are Golgi-impregnated, then gold-toned and examined in the electron microscope, it has been shown that the dendritic spines of pyramidal neurons with cell bodies in different layers receive the degenerating callosal afferents. The spines arise from the main apical dendritic shafts and their branches, from the dendrites of the apical tufts, and in some cases from the basal dendrites of the pyramidal neurons. The shafts of some pyramidal cell apical dendrites also form asymmetric synapses with callosal afferents. Since we have encountered no spiny non-pyramidal neurons in Golgi preparations of rat auditory cortex, and because other types of non-pyramidal cells have few dendritic spines, it is concluded that practically all of the dendritic spines synapsing with callosal afferents originate from pyramidal neurons.     

Ultrastructural changes in the dorsal motor nucleus of monkey following bilateral cervical vagotomy

Summary The neurons of the dorsal motor nucleas (DMN) of the monkey (Macaca fascicularis) were of two main types: small (13 × 8 m) and medium-sized (20 × 13 m). The latter, which were the predominant form, contained a pale oval nucleus surrounded by organelle-rich cytoplasm. Between one and three long principal dendrites per section profile arose from eac¹ of the somata. Both axosomatic and axodendritic synapses were seen on these cells although the latter were more common.No structural changes were noted in the DMN 1–3 days after bilateral cervical vagotomy. Some of the dendrites of the medium-sized axotomized vagal neurons appeared darkened 5–10 days after the operation. With longer surviving intervals, i.e. 21 and 28 days after operation, darkened dendrites were more commonly seen and the cytoplasmic density of these dendrites was dramatically enhanced. Their mitochondria were pale and some of them also showed vesiculation. Both normal and degenerating axon terminals were seen to form synaptic contacts with the darkened dendrites. The degenerating axon terminals were characterized by the clumping of their round agranular vesicles. Both darkened dendrites and degenerating axon terminals were phagocytosed by hypertrophied astrocytes and activated microglial cells. Blood elements infiltrating into the DMN were a possible source for some of the neural macrophages.It was concluded from the present study that the dendrites of the vagal neurons were the first structures to degenerate in axotomy and these were subsequently removed by glial elements. Degenerating axon terminals on the darkened dendrites could represent endings of the central processes of peripheral vagal ganglion cells that had undergonetransganglionic degeneration after damage to their peripheral processes.     

A golgi and a combined Golgi/GABA immunogold study of local circuit neurons in the homing pigeon hippocampus

Three types of local circuit neurons have recently been reported in the homing pigeon hippocampus. The principal type appears to be constituted by the medium-sized angular or ovoid local circuit neurons that occur in all layers of the hippocampus. The current Golgi study has revealed that these neurons can be classified according to their axonal arborisation extension: (1) in all directions, (2) principally medio-laterally, or (3) dorso-ventrally. The local circuit neurons with dorso-ventral axon arborisation are present only in the subpyramidal layer. Serial sections of a Golgi-impregnated medium-sized, multiangular local circuit neuron in the pyramidal layer and a small, ovoid neuron in the suprapyramidal layer were investigated in the electron microscope. Some of these sections were processed for GABA immunogold cytochemistry. The soma and large dendrites of both neurons displayed GABA immunogold labelling. On the soma of medium-sized local circuit neuron there were numerous terminals; on the soma of the small one relatively fewer terminals were observed. The terminals contained round and/or flat synaptic vesicles. The long axonal branches of the neurons exhibited varicosities containing flattened or pleomorphic vesicles. Axo-dendritic, axo-somatic and a few axo-axonic synapses were observed. The large dense axon arborisation field of medium-sized local circuit neurons is properly situated to modulate intrinsic hippocampal activity and that of the small local circuit neurons is well situated to modulate the hippocampal input in the suprapyramidal layer.     

Local circuit neurons in both the dentate gyrus and Ammon's horn establish synaptic connections with principal neurons in five day old rats: a morphological basis for inhibition in early development

Summary Glutamate decarboxylase (GAD)-positive and Golgi impregnated local circuit neurons of the hippocampal formation of five day old rats were examined in light and electron microscopic preparations. The ultrastructural features of these neurons were similar in both the dentate gyrus and CA1 area of Ammon's horn. Somata displayed a perikaryal cytoplasm rich in organelles but lacked organized Nissl bodies. Most nuclei showed intranuclear infoldings of varying degrees but no intranuclear sheets or rods were found. Somata and dendrites were contacted by relatively immature axon terminals that formed mainly symmetric synapses. The axons of local circuit neurons in both the dentate gyrus and Ammon's horn formed symmetric synapses with somata and dendrites of the principal neurons in these regions. Thus, both GAD-positive and Golgi-impregnated terminals of local circuit neurons were observed to form synapses with pyramidal and granule cells. These terminals were usually small and contained relatively few pleomorphic synaptic vesicles. The results show that a circuitry for inhibition is established in the 5 day old dentate gyrus and Ammon's horn, even though the local circuit neurons lack some of the typical adult ultrastructural features at this age.     

Thalamic inputs to identified commissural neurons in the monkey somatic sensory cortex

Summary Commissurally projecting neurons were identified in the monkey first somatic sensory area (SI) by the retrograde axonal transport of horseradish peroxidase (HRP) injected into the contralateral cortex. Neurons identified in this way have large pyramidal somata primarily in layer IIIB of the SI area. Their basal dendrites lie within the terminal plexus of thalamocortical afferents.Electron microscopy was used to examine the synaptic relations of the labelled commissural cells, in particular to determine whether they receive monosynaptic thalamic connections. To do this, retrogradely labelled commissural cells and Golgi-impregnated large pyramidal neurons from layer IIIB were examined ultrastructurally in material in which thalamocortical terminals were degenerating due to a prior lesion of the thalamus. In a significant number of cases degenerating terminals were found to make synapses on the spines or shafts of labelled dendrites.Injections of HRP into SI or into the white matter adjacent to the corpus callosum labelled callosal axons and terminals in the opposite SI. These axons terminated mainly near the somata of the layer IIIB pyramidal cells. Some of their terminals were found to synapse with dendrites receiving synaptic contacts from thalamocortical axon terminals.     

A combined Golgi-electron microscopic study of non-pyramidal neurons in the CA 1 area of the hippocampus

Summary Non-pyramidal neurons of the CA 1 area of the rat hippocampus were identified with a combined Golgi-electron microscopic method. They were observed to have distinctive light and electron microscopic characteristics that are different from those of pyramidal cells. These features included smooth dendrites, locally arborizing axons, infolded cell nuclei with intranuclear rods or sheets, and a well-developed perikaryal cytoplasm with many organelles. In addition, the axon terminals that contact the somata and dendrites of local circuit neurons may form asymmetric as well as symmetric synapses. The axons of these cells form symmetric synapses with dendrites and somata of pyramidal cells. Some of these features were utilized to identify non-pyramidal neurons of the CA 1 area for studies of connectivity. Degenerating commissural terminals were found to form synapses with the dendrites and somata of non-pyramidal neurons. These results indicate that these neurons are a significant population of hippocampal neurons that may provide feed-forward inhibition of pyramidal neurons.     

猫三叉神经尾侧脊束核—丘脑—皮质通路在丘脑水平的突触联系

本文采用HRP逆行追踪与顺行溃变结合法对猫三叉神经尾侧脊束核-丘脑-皮质通路在丘脑腹后内侧核内的突触联系型式进行了研究。在电镜下发现,丘脑腹后内侧核內有五种突触联系形式:(1)溃变轴突终末与HRP标记树突形成轴-树突触;(2)溃变轴突终末与HRP标记的胞体形成轴-体突触,上述两类突触型式为该通路在丘脑水平的直接突触联系方式,此外尚有(3)溃变轴突终末与非HRP标记的树突形成的轴-树突触;(4)HRP标记树突与非溃变轴突终末形成轴一树突触;(5)HRP标记树突与非HRP标记的含有突触小泡的突触前树突形成的树-树突触。本文首次报道了三叉丘系纤维与丘脑皮质投射神经元间的直接突触联系方式为轴-树和轴-体突触。同时也发现了以树突为中心的突触复合体,它是该通路在丘脑水平的一个显著特点。     

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex, IV terminations upon spiny dendrites

Summary The forms of the spiny dendrites in layer IV receiving degenerating thalamocortical axon terminals have been examined in serial thin sections. Reconstructions of segments of these dendrites show that the axon terminals synapse with both the dendritic spines and the dendritic shafts. No main shafts of apical dendrites of pyramidal neurons were found to synapse with the thalamic afferents, which are received mainly by spiny dendrites 1–2 m in diameter, at least some of which appear to be the oblique branches of apical dendrites. The forms of these postsynaptic dendrites are so variable that is is concluded they arise from more than one morphological type of neuron. The conclusion based on this and previous articles in the series is that most neuronal elements in layer IV which form asymmetric synaptic junctions are potential recipients of the thalamocortical afferents.     

Parvalbumin-immunoreactive neurons in the entorhinal cortex of the rat: localization, morphology, connectivity and ultrastructure

Summary We studied the distribution, morphology, ultrastructure and connectivity of parvalbumin-immunoreactive neurons in the entorhinal cortex of the rat. Immunoreactive cell bodies were found in all layers of the entorhinal cortex except layer I. The highest numbers were observed in layers II and III of the dorsal division of the lateral entorhinal area whereas the lowest numbers occurred in the ventral division of the lateral entorhinal area, Most such neurons displayed multipolar configurations with smooth dendrites. We distinguished a type with long dendrites and a type with short dendrites. We also observed pyramidal immunoreactive neurons. A dense plexus of immunoreactive dendrites and axons was prominent in layers II and III of the dorsal division of the lateral entorhinal area and the medial entorhinal area. None of the parvalbuminimmunoreactive cells became retrogradely labelled after injection of horseradish peroxidase into the hippocampal formation. By electron microscopy, immunoreactivity was observed in cell bodies, dendrites, myelinated and unmyelinated axons and axon terminals. Immunoreactive dendrites and axons occurred in all cortical layers. We noted many myelinated immunoreactive axons. Immunoreactive axon terminals were medium sized, contained pleomorphic synaptic vesicles, and established symmetrical synapses. Both horseradish peroxidase labelled and unlabelled immunonegative cell bodies often received synapses from immunopositive axon terminals arranged in baskets. Synapses between immunoreactive axon terminals and unlabelled dendritic shafts and spines were abundant. Synapses with initial axon segments occurred less frequently. In addition, synaptic contacts were present between immunopositive axon terminals and cell bodies and dendrites. Thus, the several types of parvalbumin-containing neuron in the entorhinal cortex are interneurons, connected to one another and to immunonegative neurons through a network of synaptic contacts. Immunonegative cells projecting to the hippocampal formation receive axo-somatic basket synapses from immunopositive terminals. This connectivity may form the morphological substrate underlying the reported strong inhibition of cells in layers II and III of the entorhinal cortex projecting to the hippocampal formation.     

Effects of intraneural injection of Ricinus communis agglutinin-60 into rat vagus nerve

Summary The dorsal motor nucleus (DMN) of the rat was studied at various survival periods following an intraneural injection ofRicinus communis agglutinin-60 (RCA-60) into the vagus nerve at the mid-cervical region. No obvious structural changes were noted in the DMN 2 and 4 days after the injection of RCA-60. At 5 and 6 days after the RCA-60 injection, the larger neurons (measuring 19 × 12 m) in the DMN underwent chromatolytic degeneration whereas the smaller ones (measuring 10 × 6 m), characterized by their infolded nuclei, remained unaffected. The majority of the degenerating DMN neurons became pale and crenated in outline. Other structural changes included swollen mitochondria with disrupted cristae and profiles of rough endoplasmic reticulum denuded of ribosome particles. A few of the degenerating neurons became extremely condensed and darkened. Axon terminals which showed synaptic contacts with these cells remained normal. Both pale and darkened degenerating dendrites, derived from the degenerating neurons, were present in the neuropil. In addition to these, degenerating axon terminals with clumping or swelling of synaptic vesicles were also present. They were presynaptic to dendrites of various sizes. Massive infiltration of mononuclear cells occurred in the DMN. These cells reached the DMN by diapedesis and were actively engaged in the phagocytosis of degenerating neuronal elements. While most of the invading cells transformed into active neuronal macrophages, some of them eventually died in the neuropil of the DMN.Light microscopic study by Fink-Heimer's method for degenerating fibres and terminals revealed their distribution to the DMN, nucleus of the tractus solitarius, nucleus commissuralis, dorsolateral and lateral part of the hypoglossal nucleus and the area postrema.It was concluded from this study that RCA-60, when injected into the cervical vagus was retrogradely transported to the cell body of the DMN neurons of the larger category. The selective destruction of the DMN neurons by RCA-60 elicited a massive infiltration of mononuclear cells which gave rise to the neural macrophages. The RCA-60 injected also killed the vagal sensory neurons as demonstrated by the numerous degenerating fibres and axon terminals in the DMN which would represent their central processes.     

Distribution of thalamic input to different dendrites of a spiny stellate cell in mouse sensorimotor cortex

A Golgi impregnated, gold-toned [2] spiney stellate cell from layer IV of mouse SmI cortex was reconstructed in three dimensions from serial thin sections to assess the apatial relationships of the synapses onto its dendrites. The distribution of thalamocortical (TC) synapses with the reconstructed dendrites is presented in this report. Thalamocortical axon terminals were labeled by lesion induced degeneration which, in mouse SmI cortex, may reliably indicate the numbers of thalamocortical axon terminals. Results indicate that thalamocortical synapses, which are distributed over most regions of the dendritic tree, are arranged in a regular, periodic fashion on parts of two of the reconstructed dendrites. In these regions, the necks of spines receiving thalamocortical input attach to the dendrite shaft at intervals of about 5 micrometers. In many other regions of the dendritic tree, two spines receiving thalamocortical synapses are separated by a similar interval. Further studies are expected to determine the extent to which dendrites of spiny stellate cells and of other kinds of cortical neurons are contacted in a periodic fashion by thalamocortical axon terminals.     

下丘脑室旁核神经元多重神经支配的电镜研究

为了探讨下丘脑神经内分泌的突触调控机制，本文用电镜细胞化学与免疫电镜双标技术相结合的方法，研究了大鼠下丘脑室旁核神经元的多重神经支配。即先用６－ＯＨＤＡ损毁ＣＡ能神经末梢，再于振动切片上用包埋前免疫电镜法，分别以ＤＡＢ和ＴＡＢ为呈色剂先后对肽能（ＯＴ或ＳＰ）神经元和ＧＡＢＡ神经元进行双重标记。电镜观察结果表明：在下丘脑室旁核内存在肽能（ＯＴ，ＳＰ）和氨基酸（ＧＡＢＡ）能神经元及ＣＡ神经末梢；ＯＴ神     

皮质—脑桥核—小脑通路的HRP结合溃变电镜法研究

目的：观察大鼠脑桥核内皮质纤维终末的溃疡变型及其与脑桥核小脑投射神经元的突触联系方式,方法：采用HRP逆行标记结合溃变电镜技术。结果：（1）皮质纤维终末出现电子致密和微丝增生两种溃变类型。以电子致密型为主。后者终末又有两种不同形态,即含圆形清亮型小泡和多形清亮型小泡者,以圆形清亮型小泡终末占优势。（2）皮质纤维终末与脑桥核小脑投射神经元形成轴－树和少量轴－体突触,部分溃变终末与HRP标记的投射神经元形成单突触联系,结论：皮质纤维与脑桥核小脑投射神经元间存在的单突触联系构成了皮持－脑桥核－小脑通路。     

Structural features of synaptic connections between descending systems and spinal neurons in the cat

The degeneration of axon terminals of the lateral (cortico and rubrospinal) and ventral (vestibulo- and reticulospinal) descending and propriospinal (lateral and ventral funiculus) systems was investigated by electron microscopy in the cat spinal cord. We studied the mean diameters of axon terminals, their arrangement on the neuronal structures in the grey matter, as well as the variety of the destructive changes in synaptic terminals. The average size of the ‘dark’ type degenerating axon terminals of fibers in the lateral descending systems was smaller than that of the ‘light’ type degenerating axon terminals in the medial descending systems. The average size of the both ‘dark’ and ‘light’ type degenerating propriospinal terminals of the ventral funiculus differed from those of the lateral funiculus.The findings concerning the sizes of synaptic terminals of the different descending and propriospinal systems correlate to a certain extent with the electrophysiological data about the nature of their synaptic action upon the spinal neurons.     

A quantitative ultrastructural analysis of neurotensin-like immunoreactive terminals in the midbrain periaqueductal gray: analysis of their possible relationship to periaqueductal gray-raphe magnus projection neurons

The periaqueductal gray of the rat contains significant levels of the putative peptide neurotransmitter neurotensin. The profound anti-nociceptive effects of neurotensin injected into the periaqueductal gray may involve a population of periaqueductal gray neurons having descending projections to the rostral ventral medulla, including nucleus raphe magnus and adjacent reticular nuclei. In this study, electron microscopic immunocytochemistry was used to examine the ultrastructure of periaqueductal gray axon terminals containing neurotensin-like immunoreactive material and to obtain quantitative data regarding the relationship of such terminals to other elements of the neuropil. Of particular interest was the interaction between neurotensin-like immunoreactive terminals and retrogradely labeled neurons that project to nucleus raphe magnus and adjacent reticular nuclei. Within the periaqueductal gray, the sites of retrograde and immuno-labeling were consistent with previous reports. The neurotensin-immunoreactive structures were predominantly axon fibers and terminals. In the ventrocaudal periaqueductal gray, the mean diameter of neurotensin-containing terminals was 0.93 +/- 0.02 micron and they comprised a volume fraction of 0.0010. Most of the neurotensin-positive terminals examined (74.2%) were in contact with or closely apposed to dendrites. The most common anatomical configuration observed was a single neurotensin-immunoreactive terminal juxtaposed to three dendrites. Only 2% of immunoreactive terminals were apposed to perikarya. Neurotensin-immunoreactive terminals were observed to form symmetrical synapses and 96.4% of such terminals were axodendritic. Occasional multiple neurotensin-immunoreactive terminals associated with single dendrites were observed. Although neurotensin-like immunoreactive terminals were quite prominent, only a small percentage made synaptic contact with periaqueductal gray neurons that project to the nucleus raphe magnus and adjacent reticular formation. Among the population of periaqueductal gray neurons retrogradely-labeled from nucleus raphe magnus and adjacent reticular nuclei, the frequency of direct synaptic contact by neurotensin-immunoreactive terminals was 2%. These data suggest that the periaqueductal gray circuitry by which neurotensin ultimately affects descending pathways is complex and may involve a population of local circuit neurons whose transmitters and connections remain to be elucidated.     

The neocortex

By way of introduction, an outline is presented of the origin and evolutionary development of the neocortex. A cortical formation is lacking in amphibians, but a simple three-layered cortex is present throughout the pallium of reptiles. In mammals, two three-layered cortical structures, i.e. the prepiriform cortex and the hippocampus, are separated from each other by a six-layered neocortex. Still small in marsupials and insectivores, this “new” structure attains amazing dimensions in anthropoids and cetaceans. Neocortical neurons can be allocated to one of two basic categories: pyramidal and nonpyramidal cells. The pyramidal neurons form the principal elements in neocortical circuitry, accounting for at least 70% of the total neorcortical population. The evolutionary development of the pyramidal neurons can be traced from simple, “extraverted” neurons in the amphibian pallium, via pyramid-like neurons in the reptilian cortex to the fully developed neocortical elements designated by Cajal as “psychic cells”. Typical mammalian pyramidal neurons have the following eight features in common: (1) spiny dendrites, (2) a stout radially oriented apical dendrite, forming (3) a terminal bouquet in the most superficial cortical layer, (4) a set of basal dendrites, (5) an axon descending to the subcortical white matter, (6) a number of intracortical axon collaterals, (7) terminals establishing synaptic contacts of the round vesicle/asymmetric variety, and (8) the use of the excitatory aminoacids glutamate and/or aspartate as their neurotransmitter. The pyramidal neurons constitute the sole output and the largest input system of the neocortex. They form the principal targets of the axon collaterals of other pyramidal neurons, as well as of the endings of the main axons of cortico-cortical neurons. Indeed, the pyramidal neurons constitute together a continuous network extending over the entire neocortex, justifying the generalization: the neocortex communicates first and foremost within itself. The typical pyramidal neurons represent the end stage of a progressive evolutionary process. During further development many of these elements have become transformed by reduction into various kinds of atypical or aberrant pyramidal neurons. Interestingly, none of the six morphological characteristics, mentioned above under 1–6, has appeared to be unassailable; pyramidal neurons lacking spines, apical dendrites, long axons and intracortical axon collaterals etc. have all been described. From an evolutionary point of view the typical pyramidal neurons represent not only the principal neocortical elements, but also the source of various excitatory local circuit neurons. The spiny stellate cells, which are abundant in highly specialized primary sensory areas, form a remarkable case in point. In these elements only two of the six original pyramidal attributes, i.e. spiny dendrites and an intracortical axonal arbor, are retained. The nonpyramidal neurons display a diverse morphology, but share a number of important morphological and functional features: (1) their dendrites bear only a few spines or none, (2) their axons do not leave the cortex, (3) their terminals make synapses of the flat vesicle/symmetric variety, (4) they use the inhibitory neurotransmitter GABA, and (5) almost all types make synaptic contacts with pyramidal neurons. Several subclasses of nonpyramidal neurons are selectively immunoreactive for particular calcium-binding proteins. The widely held notion that the pyramidal neurons constitute the relatively constant basic framework of the cortex, whereas the local circuit neurons are variable and increase during phylogenetic development in number as well as in diversity is untenable. A survey is presented of the structure, synaptology and chemodifferentiation of the various neocortical cell types, allocating them to three groups: pyramidal neurons, excitatory interneurons and inhibitory interneurons. The synaptic relations of the various neocortical neurons are pictorially summarized in two microcircuitry diagrams, which together form the pièce de résistance of the present treatise. The various approaches to the structure of the neocortex are discussed. It is emphasized that correlative structural, ultrastructural and electrophysiological studies of pyramidal neurons known to project to a given cortical or subcortical target form a promising field of interdisciplinary research.