Cholinergic synaptic circuitry in the macaque prefrontal cortex

Surprisingly little is known about the synaptic architecture of the cholinergic innervation in the primate cerebral cortex in spite of its acknowledged relevance to cognitive processing and Alzheimer's disease. To address this knowledge gap, we examined serially sectioned cholinergic axons in supra- and infragranular layers of the macaque prefrontal cortex by using an antibody against the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The tissue bound antibody was visualized with both immunoperoxidase and silver-enhanced diaminobenzidine sulfide (SEDS) techniques. Both methods revealed that cholinergic axons make synapses in all cortical layers and that these synapses are exclusively symmetric. Cholinergic axons formed synapses primarily on dendritic shafts (70.5%), dendritic spines (25%), and, to a lesser extent, cell bodies (4.5%). Both pyramidal neurons and cells exhibiting the morphological features of GABAergic cells were targets of the cholinergic innervation. Some spiny dendritic shafts received multiple, closely spaced synapses, suggesting that a subset of pyramidal neurons may be subject to a particularly strong cholinergic influence. Analysis of synaptic incidence of cholinergic profiles in the supragranular layers of the prefrontal cortex by the SEDS technique revealed that definitive synaptic junctions were formed by 44% of the cholinergic boutons. An unexpected finding was that chohnergic boutons were frequently apposed to spines and small dendrites without making any visible synaptic specializations. These same spines and dendrites often received asymmetric synapses, presumably of thalamocortical or corticocortical origin. Present ultrastructural findings suggest that acetylcholine may have a dual modulatory effect in the neocortex: one through classical synaptic junctions on dendritic shafts and spines, and the other through nonsynaptic appositions in close vicinity to asymmetric synapses. Further physiological studies are necessary to test the hypothesis of the nonsynaptic release of acetylcholine in the Cortex. © 1995 Wiley-Liss, Inc.     

Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms

Current understanding of the synaptic organization of the brain depends to a large extent on knowledge about the synaptic inputs to the neurons. Indeed, the dendritic surfaces of pyramidal cells (the most common neuron in the cerebral cortex) are covered by thin protrusions named dendritic spines. These represent the targets of most excitatory synapses in the cerebral cortex and therefore, dendritic spines prove critical in learning, memory and cognition. This paper presents a new method that facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns. This method is based both on the implementation of straightening and unrolling transformations to move the analysis process to a planar, unfolded arrangement, and on the design of DISPINE, an interactive environment that supports the visual analysis of 3D patterns.     

Light and electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex.

The distribution and synaptic connections of dopamine axons were studied by light and electron microscopy in human cerebral cortex. For this purpose, dopamine immunoreactivity was characterized in apparently normal anteriolateral temporal cortex, which was removed to gain access to the medial temporal lobe during tumor excision or treatment of epilepsy. Nissl sections showed this to be granular neocortex. Dopamine fibers were distributed throughout this cortex, although there were relatively more fibers in layers I-II and in layers V-VIa, compared to layers III-IV and VIb, resulting in a bilaminar pattern of labeling. In all layers, fibers were seen to form numerous varicosities, and to vary in size from thick to very fine. Fibers were relatively straight, sparsely branched and were oriented in various planes within the cortex. However, in layer I, they often ran parallel to the pial surface. In order to analyze the functional interactions of dopamine fibers, individual cortical layers were surveyed for dopamine synapses. These were usually symmetrical (Gray's type II), although 13% of them were asymmetrical. Approximately 60% of dopamine synapses were made with dendritic spines, and 40% with dendritic shafts, and this ratio was similar in all layers. On both spines and shafts, it was common to see dopamine synapses closely apposed to an unlabeled asymmetric input, suggesting a dopamine modulation of excitatory input. Some postsynaptic dendritic shafts had features of pyramidal cells, including formation of spines. Since pyramidal cells are the major type of cortical spiny neuron, they probably represent the main target of dopamine synapses in this cortex. There were also dopamine profiles apposed to membrane densities on unlabeled axon terminals, suggesting another type of synaptic interaction. These findings provide the first documentation of dopamine synapses in the human cortex, and show that they form classical synaptic junctions. The location of these synapses on spines and distal dendrites, and their proximity to asymmetric synapses, suggest a modulatory role on excitatory input to pyramidal cells.     

Olfactory learning is associated with increased spine density along apical dendrites of pyramidal neurons in the rat piriform cortex

We studied the effect of olfactory learning on the dendritic spine density of pyramidal neurons in the rat piriform (olfactory) cortex. Rats were trained to distinguish between two pairs of odours in an olfactory discrimination task. Three days after training completion, rats were killed and layer II pyramidal neurons identified by Golgi impregnation were examined with a light microscope. Counts of visible spines were performed along the secondary and tertiary branches of both the apical dendrites and the basal dendrites, which are the sites of intracortical synaptic inputs. An estimate of the true spine density was obtained using Feldman and Peters' method (1979, The Journal of Comparative Neurology, 188, 527--542). The estimated true spine density along apical dendrites was higher in neurons from trained rats than those in pseudotrained and naive rats by 15%. As length of spiny dendrites did not change significantly after learning, the learning-related increase in spine density in neurons from trained rats may indicate on an increased number of excitatory synapses interconnecting pyramidal neurons in the piriform cortex, following olfactory learning.     

The Convergence of Axon Terminals from the Mediodorsal Thalamic Nucleus and Ventral Tegmental Area on Pyramidal Cells in Layer V of the Rat Prelimbic Cortex

We investigated the ultrastructural basis of the synaptic convergence of afferent fibres from the mediodorsal thalamic nucleus (MD) and the ventral tegmental area (VTA) on the prefrontal cortical neurons of the rat by examining the synaptic relationships between thalamocortical or tegmentocortical terminals labelled with anterograde markers [lesion-induced degeneration or transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA—HRP)] and randomly selected unlabelled apical dendrites of layer V pyramidal cells in the prelimbic cortex. WGA—HRP-labelled terminals from the VTA ranged in diameter from 0.7 to 2.8 μm and established synaptic contacts with large dendritic profiles, i.e. proximal segments of apical dendritic shafts and spines from layer V pyramidal cells. Symmetrical synapses, i.e. inhibitory synapses, were more often seen than asymmetrical ones. Degenerating terminals from the MD formed asymmetrical synapses on dendritic spines or occasionally on small dendritic shafts of apical dendrites from layer V pyramidal cells, which received tegmentocortical synapses, mostly within layer III. Thalamocortical synapses were more distally distributed over common apical dendrites than tegmentocortical synapses, although some of them overlapped. The numerical density of direct synaptic inputs from the MD and VTA was low. These results suggest that fibres from the VTA exert their inhibitory effects directly on pyramidal cells in layer V via synaptic junctions with apical dendrites of these pyramidal cells, and that the tegmentocortical fibres are in an ideal anatomical position to modulate the reverberatory circuits between the MD and the prelimbic cortex.     

Map of the synapses formed with the dendrites of spiny stellate neurons of cat visual cortex

The synaptic input of six spiny stellate neurons in sublamina 4A of cat area 17 was assessed by electron microscopy. The neurons were physiologically characterized and filled with horseradish peroxidase in vivo. After processing the neurons were reconstructed at the light microscopic level using computer-assisted methods and analyzed quantitatively. The extensive branching of the dendritic tree about 50 μm from the soma meant that the distal branches constituted five times the length of proximal dendrite. Proximal and distal portions of a single dendrite from each neuron were examined in series of ultrathin sections (1,456 sections) in the electron microscope. The majority (79%) of the 263 synapses examined were asymmetric; the remainder (21%) were symmetric. Symmetric synapses formed 35% of synapses sampled on proximal dendrites and were usually located on the shaft. They formed only 4% of synapses sampled on distal dendrites. Spines accounted for less than half of the total asymmetric synapses (45%); the remainder were on shafts. Symmetric synapses formed with four of 92 spines. Nine spines formed no synapses. Spiny stellate neurons in cat visual cortex appear to differ considerably from pyramidal neurons in having a significant asymmetric (excitatory) synaptic input to the dendritic shaft.     

Callosal terminals in the rat prefrontal cortex: Synaptic targets and association with GABA-immunoreactive structures

The callosal projections of the cerebral cortex play an important role in the functional integration of the two hemispheres, and the anatomy of these connections has been extensively studied in primary sensory and motor regions. In the present investigation, we examined the synaptic targets of callosal terminals in a limbic association area, the prefrontal cortex (PFC) in the rat. In addition, we examined the relationship of callosal afferents to GABA local circuit neurons within the PFC. Callosal terminals were labeled by either anterograde transport of Phaseolus vulgaris leucoagglutinin from superficial or deep layers or by anterograde degeneration following electrolytic lesion of the contralateral PFC. Callosal terminals in either the superficial or deep layers labeled by either method formed primarily asymmetric axo-spinous synapses (approximately 95%), while the remainder formed axo-dendritic synapses. Some of the dendrites postsynaptic to callosal terminals exhibited a morphology characteristic of local circuit neurons. This observation was confirmed in tissue immunolabeled for GABA, in which degenerating callosal terminals sometimes formed asymmetric synapses on GABA-labeled dendrites. In addition, GABA-labeled terminals and callosal afferents were sometimes observed to converge onto common postsynaptic dendritic shafts or spines within the PFC. These results indicate that callosal terminals in limbic association cortex, consistent with sensory and motor cortices, primarily target the spines of pyramidal neurons. In addition, the results suggest that callosal afferents to the PFC interact with GABA local circuit neurons at multiple levels. Specifically, a proportion of callosal terminals appear to provide excitatory drive to GABA cells, while GABA terminals may modulate the excitation from callosal inputs to the distal dendrites and spines of PFC pyramidal neurons. Synapse 29:193–205, 1998. © 1998 Wiley-Liss, Inc.     

Quantification of thalamocortical synapses with spiny stellate neurons in layer IV of mouse somatosensory cortex

The distribution of thalamocortical (TC) and other synapses involving spiny stellate neurons in layer IV of the barrel region of mouse primary somatosensory cortex (SmI) was examined in seven male CD/1 mice. TC axon terminals were labeled by lesion-induced degeneration, which has been shown to label reliably all TC synapses in mouse barrel cortex. Spiny stellate neurons, labeled by Golgi impregnation and gold toning, were identified with the light microscope prior to thin sectioning and electron microscopy. Analysis of eight dendritic segments from seven spiny stellate neurons showed that most of their synapses are with their dendritic spines, rather than with their shafts. Axospinous synapses are primarily of the asymmetrical type, whereas axodendritic synapses are mainly of the symmetrical type. Dendrites of spiny stellate neurons consistently form thalamocortical synapses, most of which involve spine heads rather than spine stalks or dendritic shafts. From 10.4% to 22.9% of all asymmetrical synapses with dendrites of spiny stellate neurons involve TC axon terminals. In general, this is a higher range than the ranges that characterize the TC synaptic connectivity of dendrites belonging to other types of neurons, implying that spiny stellate neurons are perhaps more strongly influenced by TC synaptic input than other types of cortical neurons examined previously. Spines involved in TC synapses were distributed irregularly along each of the stellate cell dendrites; about half of the interspinous intervals between these spines were about 5 microns or less. Modulations of the efficacy of TC synaptic input to dendrites of layer IV spiny stellate neurons are discussed in the light of recently reported computer simulated analyses of axospinous synaptic connections.     

Fine structure and synaptic connections of the common spiny neuron of the rat neostriatum: A study employing intracellular injection of horseradish peroxidase

Medium-sized spiny neurons of the rat neostriatum, identified by intracellular injection of horseradish peroxidase, were examined at both light and electron microscopic levels. These neurons were characterized by their heavy investment of dendritic spines, beginning about 20 μm from the soma and continuing to the tips of the dendrites. Their axons arose from the soma or from a large dendritic trunk very near the soma, and tapered rapidly to form a main axonal branch from which arose several smaller initial collaterals. These arborized extensively throughout an area of about the same size as, and highly overlapping with, the dendritic field of the cell, while the main axon could be followed for distances of up to 1 mm in the direction of the globus pallidus. Three major synaptic types were seen in contact with spiny neurons. Boutons containing small round synaptic vesicles formed synapses exclusively with spiny regions of the dendrites, and most of these were axo-spinous. Small, very pleomorphic synaptic vesicles characterized a second bouton type of unknown origin, which made contacts with somata, initial segments, and dendrites, but not dendritic spines. Boutons containing large pleomorphic synaptic vesicles had the most widespread distribution, contacting all regions including dendritic spines. Spines receiving these contacts also were postsynaptic to boutons containing small round vesicles. Axon collaterals of spiny cells formed synapses with large pleomorphic vesicles and made synapses with somata, initial segments of axons, dendrites, and dendritic spines of striatal neurons, including other spiny cells.     

Synaptic termination of afferents from the ventrolateral nucleus of the thalamus in the cat motor cortex. A light and electron microscopy study

The synaptic termination in the cat motor cortex of afferents from the ventrolateral nucleus of the thalamus (VL) has been studied with experimental light and electron microscopic methods. The distribution of normal synapses on motor cortex pyramidal, stellate, and Betz cells was also examined. Synapses in the motor cortex can be classified into two general types. The first and most prominent type contains flat vesicles, lacks a compact postsynaptic density, and corresponds to Colonnier's ('68) symmetrical synapse. Stellate neurons receive synapses of both types on their cell bodies and proximal dendritic shafts, while pyramidal cells have only symmetrical synapses at these sites. The dendritic spines of both stellate and pyramidal cells are contacted by predominantly asymmetrical synapses. Betz cells, like smaller pyramidal neurons, receive only symmetrical synapses on their cell bodies. The proximal portions of the Betz cells apical dendrites, however, receive both asymmetrical and symmetrical synapses. Following VL lesions, degenerating synapses were mainly found in three cortical layers: the upper third of layer I (18%), layer III (66%), and layer VI (13%). Degenerating synapses were not seen in the lower two-thirds of layer I or in layer II, and were only rarely seen in layer V (3%). Ninety-one percent of the VL synapses were found on spines and 8% on stellate-type dendritic shafts. Stellate cell bodies rarely received VL synapses (1%) and none occurred on pyramidal or Betz cell bodies and their proximal dendrites. A VL synapse within layer III was found on two dendritic spines of a Betz cell apical dendrite. Thus, part of the VL input to layer III synapses on the processes of both motor cortex output neurons (Betz cells in layer V) and cortical interneurons (stellate cells in layer III).     

Synaptology of the proximal segment of pyramidal cell basal dendrites

Pyramidal neurons are covered with dendritic spines, the main postsynaptic targets of excitatory (asymmetrical) synapses. However, the proximal portion of both the apical and basal dendrites is devoid of spines, suggesting a lack of excitatory inputs to this region. In the present study we used electron microscopy to analyse the proximal region of the basal dendrites of supra- and infragranular pyramidal cells to determine if this is the case. The proximal region of 80 basal dendrites sampled from the rat hindlimb representation in the primary somatosensory cortex was studied by electron microscopy. A total of 317 synapses were found within this region of the dendrites, all of which were of the symmetrical type. These results suggest that glutamate receptors, although present in the cytoplasm, are not involved in synaptic junctions in the proximal portion of the dendrites. These data further support the idea that inhibitory terminals exclusively innervate the proximal region of basal dendrites.     

The morphology and synaptic connections of spiny stellate neurons in monkey visual cortex (area 17): a Golgi-electron microscopic study

Based on a gold-toning, Golgi-electron microscope examination of 12 small and medium-sized spiny stellate neurons in laminae 4A, 4B, and 4C of the monkey visual cortex (area 17), the ultrastructure of the cell somata, dendrites, and axons of these neurons is described. Particular attention is paid to the synapses involving the surface of different parts of these neurons. Only symmetric synapses occur on the somata of spiny stellate neurons, and these occur with a frequency of 11.0-15.9 synapses/100 microns2 perikaryal surface. Symmetric synapses also occur on dendritic shafts and, occasionally, on dendritic spines. Asymmetric synapses are occasionally present along the dendritic shafts of spiny stellate neurons, but the majority of asymmetric synapses (75-95%) occur on their dendritic spines. The initial axon segments of the smallest spiny stellate neurons possess no axo-axonal synapses, but several symmetric synapses are present along the initial segment of a medium-sized, spiny stellate neuron in layer 4B. Fifty-three synapses made by boutons of the axons of these spiny stellate neurons have been identified, and all are asymmetric. Sixty per cent of the synapses are formed by boutons en passant and the remainder by the terminal swellings of spine-like axonal appendages, boutons terminaux. Of the synapses formed by the axons of spiny stellate cells, axo-spinous synapses outnumber axo-dendritic synapses two to one, and axo-dendritic synapses involve both spinous and aspinous dendrites. Evidence is presented which suggests that many of the axon terminals forming asymmetric synapses with the dendritic shafts and spines of spiny stellate neurons are derived from other spiny stellate neurons.     

Ultrastructural analysis of synaptic relationships of intracellularly stained pyramidal cell axons in piriform cortex

Axons of pyramidal cells in piriform cortex stained by intracellular injection of horseradish peroxidase (HRP) have been analyzed by light and electron microscopy. Myelinated primary axons give rise to extensive, very fine caliber (0.2 micron) unmyelinated collaterals with stereotyped radiating branching patterns. Serial section electron microscopic analysis of the stained portions of the collateral systems (initial 1-2 mm) revealed that they give rise to synaptic contacts on dendritic spines and shafts. These synapses typically contain compact clusters of large, predominantly spherical synaptic vesicles subjacent to asymmetrical contacts with heavy postsynaptic densities. On the basis of comparisons with Golgi material and intracellularly stained dendrites, it was concluded that dendritic spines receiving synapses from the proximal portions of pyramidal cell axon collaterals originate primarily from pyramidal cell basal dendrites. Postsynaptic dendritic shafts contacted closely resemble dendrites of probable GABAergic neurons identified in antibody and [3H]-GABA uptake studies. Electron microscopic examination of pyramidal cell axon initial segments revealed a high density of symmetrical synaptic contacts on their surfaces. Synaptic vesicles in the presynaptic boutons were small and flattened. It is concluded that pyramidal cells synaptically interact over short distances with other pyramidal cells via basal dendrites and with deep nonpyramidal cells that probably include GABAergic cells mediating a feedback inhibition. This contrasts with long associational projections of pyramidal cells that terminate predominantly on apical dendrites of other pyramidal cells.     

Synaptic relationships between axon terminals from the mediodorsal thalamic nucleus and gamma-aminobutyric acidergic cortical cells in the prelimbic cortex of the rat

Although the reciprocal interconnections between the prefrontal cortex and the mediodorsal nucleus of the thalamus (MD) are well known, the involvement of inhibitory cortical interneurons in the neural circuit has not been fully defined. To address this issue, we conducted three combined neuroanatomical studies on the rat brain. First, the frequency and the spatial distribution of synapses made by reconstructed dendrites of nonpyramidal neurons were identified by impregnation of cortical cells with the Golgi method and identification of thalamocortical terminals by degeneration following thalamic lesions. Terminals from MD were found to make synaptic contacts with small dendritic shafts or spines of Golgi-impregnated nonpyramidal cells with very sparse dendritic spines. Second, a combined study that used anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and postembedding gamma-aminobutyric acid (GABA) immunocytochemistry indicated that PHA-L-labeled terminals from MD made synaptic junctions with GABA-immunoreactive dendritic shafts and spines. Nonlabeled dendritic spines were found to receive both axonal inputs from MD with PHA-L labelings and from GABAergic cells. In addition, synapses were found between dendritic shafts and axon terminals that were both immunoreactive for GABA. Third, synaptic connections between corticothalamic neurons that project to MD and GABAergic terminals were investigated by using wheat germ agglutinin conjugated to horseradish peroxidase and postembedding GABA immunocytochemistry. GABAergic terminals in the prelimbic cortex made symmetrical synaptic contacts with retrogradely labeled corticothalamic neurons to MD. All of the synapses were found on cell somata and thick dendritic trunks. These results provide the first demonstration of synaptic contacts in the prelimbic cortex not only between thalamocortical terminals from MD and GABAergic interneurons but also between GABAergic terminals and corticothalamic neurons that project to MD. The anatomical findings indicate that GABAergic interneurons have a modulatory influence on excitatory reverberation between MD and the prefrontal cortex.     

Targets of horizontal connections in macaque primary visual cortex.

Pyramidal neurons within the cerebral cortex are known to make long-range horizontal connections via an extensive axonal collateral system. The synaptic characteristics and specificities of these connections were studied at the ultrastructural level. Two superficial layer pyramidal cells in the primate striate cortex were labeled by intracellular injections with horseradish peroxidase (HRP) and their axon terminals were subsequently examined with the technique of electron microscopic (EM) serial reconstruction. At the light microscopic level both cells showed the characteristic pattern of widespread, clustered axon collaterals. We examined collateral clusters located near the dendritic field (proximal) and approximately 0.5 mm away (distal). The synapses were of the asymmetric/round vesicle variety (type I), and were therefore presumably excitatory. Three-quarters of the postsynaptic targets were the dendritic spines of other pyramidal cells. A few of the axodendritic synapses were with the shafts of pyramidal cells, bringing the proportion of pyramidal cell targets to 80%. The remaining labeled endings were made with the dendritic shafts of smooth stellate cells, which are presumed to be (GABA)ergic inhibitory cells. On the basis of serial reconstruction of a few of these cells and their dendrites, a likely candidate for one target inhibitory cell is the small-medium basket cell. Taken together, this pattern of outputs suggests a mixture of postsynaptic effects mediated by consequence the horizontal connections may well be the substrate for the variety of influences observed between the receptive field center and its surround.     

Pathway specificity of dendritic spine morphology in identified synapses onto rat hippocampal CA1 neurons in organotypic slices

The output of the hippocampus is largely determined by interaction of the three excitatory pathways that impinge on CA1 pyramidal neurons. These synapses, formed by axons of: (1) CA3 pyramidal neurons; (2) neurons of the entorhinal cortex (EC); and (3) neighboring CA1 neurons, are all potentially plastic. Here, we take advantage of the accessibility of the organotypic slice preparation to identify the type of spines with which each of these pathways forms synapses, at different developmental stages. Recent reports have shown that morphology of dendritic spines is activity-dependent with large mushroom spines being thought to represent stronger synaptic connections than thin or stubby spines. Although in a wide range of preparations, mushroom spines represent only 15% of spines across the whole dendritic tree, we find that this proportion is highly pathway specific. Thus in organotypic slices, the axons of CA3 neurons form synapses with mushroom spines on CA1 neurons in approximately 50% of cases, whereas this spine type is rare (<10%) in either of the other two pathways. This high proportion of mushroom spines only occurs after spontaneous excitatory activity in the CA1 cells increases over the second week in vitro. Previous studies suggest that pathway specificity also occurs in vivo. In tissue fixed in vivo, it is the synapses of distal apical dendrites thought to be formed by axons originating in the EC that are richer in mushroom spines. Hence, contrary to previous suggestions, the proportion of mushroom spines is clearly not an intrinsic property of the pathway but rather a characteristic dependent on the environment. We suggest that this is most likely a result of the previous activity of the synapses. The fact that, despite the large differences in pathway specificity between preparations, the overall proportion of different spine types remains unchanged, suggests a strong influence of homeostasis across the network.     

Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine

Repeated treatment with psychostimulant drugs produces changes in brain and behaviour that far outlast their initial neuropharmacological actions. The nature of persistent drug-induced neurobehavioural adaptations is of interest because they are thought to contribute to the development of dependence and addiction, and other forms of psychopathology, e.g. amphetamine psychosis. There are many reports that psychostimulants produce biochemical adaptations in brain monoamine systems, especially dopamine systems. The purpose of the present study was to determine if they might also alter the morphology of neurons in brain regions that receive monoaminergic innervation. Rats were given repeated injections of either amphetamine or cocaine, or, to control for general motor activity, allowed access to a running wheel. They were then left undisturbed for 24-25 days before their brains were processed for Golgi-Cox staining. Treatment with either amphetamine or cocaine (but not wheel running experience) increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex. Cocaine also increased dendritic branching and spine density on the basilar dendrites of pyramidal cells. In addition, both drugs doubled the incidence of branched spines on medium spiny neurons. It is suggested that some of the persistent neurobehavioural consequences of repeated exposure to psychostimulant drugs may be due to their ability to reorganize patterns of synaptic connectivity in the nucleus accumbens and prefrontal cortex.     

Combined golgi and electron microscopic study on the synapses formed by double bouquet cells in the visual cortex of the cat and monkey

The morphology of certain Golgi-stained cells was examined in the striate and peristriate cortex of the cat and in the striate cortex of the rhesus monkey. Neurons in layer III were selected on the basis of their characteristic vertical axon bundles, which are 20–150 μ in diameter and traverse layers II–V Selected neurons were examined under the electron microscope to characterize their synapses and to establish their postsynaptic targets. It was found that double bouquet cells form symmetrical or type II synapses. In the cat the postsynaptic membrane specialization was more extensive than in the monkey. After removing the Golgi precipitate from boutons of two cells in the cat, small pleomorphic and flattened vesicles were found in the boutons Earlier suggestions that double bouquet cells make synapses preferentially with spines of apical dendrites could not be confirmed. Out of 66 boutons in area 17 of the cat, 86.4% formed synapses with dendritic shafts, many of them belonging to nonpyramidal cells, 9% with perikarya of nonpyramidal cells, and only 4.6% with spines. Out of 19 synapses examined in area 18, 74% were contacting dendritic shafts and the rest contacted spines. In the monkey 60% of a total of 35 double bouquet cell synapses made synapses with dendritic shafts. A different type of double bouquet cell with densely spiny dendrites is also described in layer IV of the monkey striate cortex. This neuron formed asymmetrical synapses It is suggested that layer III double bouquet cells with vertical axon bundles are probably inhibitory and act on other nonpyramidal cells and certain parts of pyramidal cells.     

Columnar organization of dendrites and axons of single and synaptically coupled excitatory spiny neurons in layer 4 of the rat barrel cortex.

Cortical columns are the functional units of the neocortex that are particularly prominent in the "barrel" field of the somatosensory cortex. Here we describe the morphology of two classes of synaptically coupled excitatory neurons in layer 4 of the barrel cortex, spiny stellate, and star pyramidal cells, respectively. Within a single barrel, their somata tend to be organized in clusters. The dendritic arbors are largely confined to layer 4, except for the distal part of the apical dendrite of star pyramidal neurons that extends into layer 2/3. In contrast, the axon of both types of neurons spans the cortex from layer 1 to layer 6. The most prominent axonal projections are those to layers 4 and 2/3 where they are largely restricted to a single cortical column. In layers 5 and 6, a small fraction of axon collaterals projects also across cortical columns. Consistent with the dense axonal projection to layers 4 and 2/3, the total number and density of boutons per unit axonal length was also highest there. Electron microscopy combined with GABA postimmunogold labeling revealed that most (>90%) of the synaptic contacts were established on dendritic spines and shafts of excitatory neurons in layers 4 and 2/3. The largely columnar organization of dendrites and axons of both cell types, combined with the preferential and dense projections within cortical layers 4 and 2/3, suggests that spiny stellate and star pyramidal neurons of layer 4 serve to amplify thalamic input and relay excitation vertically within a single cortical column.     

The pyramidal neuron in cerebral cortex following prenatal X-irradiation

Pregnant rats were subjected to whole body X-irradiation amounting to 125 R, on gestational day 15. Cortical pyramidal neurons were examined in irradiated and control offspring at 4 weeks and 4 to 6 months postnatally. All gestationally irradiated rats developed ectopic cortex located below the corpus callosum adjacent to the caudate nucleus in the forebrain. With the rapid Golgi stain, counts were made of dendritic spines on the apical dendrites of layer 5 pyramidal cells in the normally-located cortex and compared with similar neurons in the ectopias. Dendritic spines were present on all pyramidal cells but spines were more sparse on ectopic pyramidal cells. Electron microscopic examination of ectopic and layered cortex in irradiated rats showed axodendritic synapses on the spines and shafts of the dendrites and axosomatic synapses, all of which were indistinguishable morphologically from synapses in control cortex. As a result of the observations made with the light and electron microscopes, it is concluded that the ectopic cortex may contain functional cells in spite of the abnormal location of the tissue.