Morphological variation of layer III pyramidal neurones in the occipitotemporal pathway of the macaque monkey visual cortex

We compared the morphological characteristics of layer III pyramidal neurones in different visual areas of the occipitotemporal cortical 'stream', which processes information related to object recognition in the visual field (including shape, colour and texture). Pyramidal cells were intracellularly injected with Lucifer Yellow in cortical slices cut tangential to the cortical layers, allowing quantitative comparisons of dendritic field morphology, spine density and cell body size between the blobs and interblobs of the primary visual area (V1), the interstripe compartments of the second visual area (V2), the fourth visual area (V4) and cytoarchitectonic area TEO. We found that the tangential dimension of basal dendritic fields of layer III pyramidal neurones increases from caudal to rostral visual areas in the occipitotemporal pathway, such that TEO cells have, on average, dendritic fields spanning an area 5-6 times larger than V1 cells. In addition, the data indicate that V1 cells located within blobs have significantly larger dendritic fields than those of interblob cells. Sholl analysis of dendritic fields demonstrated that pyramidal cells in V4 and TEO are more complex (i.e. exhibit a larger number of branches at comparable distances from the cell body) than cells in V1 or V2. Moreover, this analysis demonstrated that the dendrites of many cells in V1 cluster along specific axes, while this tendency is less marked in extrastriate areas. Most notably, there is a relatively large proportion of neurones with 'morphologically orientation-biased' dendritic fields (i.e. branches tend to cluster along two diametrically opposed directions from the cell body) in the interblobs in V1, as compared with the blobs in V1 and extrastriate areas. Finally, counts of dendritic spines along the length of basal dendrites revealed similar peak spine densities in the blobs and the interblobs of V1 and in the V2 interstripes, but markedly higher spine densities in V4 and TEO. Estimates of the number of dendritic spines on the basal dendritic fields of layer III pyramidal cells indicate that cells in V2 have on average twice as many spines as V1 cells, that V4 cells have 3.8 times as many spines as V1 cells, and that TEO cells have 7.5 times as many spines as V1 cells. These findings suggest the possibility that the complex response properties of neurones in rostral stations in the occipitotemporal pathway may, in part, be attributed to their larger and more complex basal dendritic fields, and to the increase in both number and density of spines on their basal dendrites.      

Early specification of the hierarchical organization of visual cortical areas in the macaque monkey

The laminar organization of cortico-cortical projection neurons (expressed by the percentage of supragranular projecting neurons - SLN%) characterizes cortical pathways as feedforward (FF) or feedback (FB) and determines the hierarchical ranking of cortical areas. There is evidence of a developmental reduction in SLN% of pathways to area V1. Here, by analyzing pre- and postnatal projections to area V4, we have been able to address whether developmental reductions of SLN% impact on information processing in the immature cortex. FB pathways to area V4 exhibit 28-84% reduction of SLN%. This contrasts with the FF projections, which show little or no SLN% reduction. However, SLN% values in the immature cortex allocated cortical areas to the same hierarchical levels as in the adult. The developmental reduction of SLN% is a widespread phenomenon in the neocortex and is a distinctive feature of FB pathways. Two mechanisms contribute to developmental changes in SLN%: (i) delayed ingrowth of axons into the cortical target from infragranular layer neurons and (ii) prolonged developmental reduction of the divergence of projections from supragranular layer neurons. The present results show that FF and FB projections exhibit different developmental processes and patterns of connections linking cortical areas and their hierarchical relations are established prenatally, independently of regressive phenomena.     

The morphology of the koniocellular axon pathway in the macaque monkey

The key objective of this study was to determine the distribution and morphology of koniocellular (K) lateral geniculate nucleus (LGN) axons in primary visual cortex (V1) of the macaque monkey. In particular, we were interested in understanding whether subpopulations of K axons exist in this species and, if so, if these subpopulations arise from different K layers of the LGN. Restricted injections of the tracers, biotinilated dextran amine, or Phaseolus vulgaris leucoagglutinin were targeted to specific LGN K layers under electrophysiological guidance and immunocytochemistry was used to visualize labeled axons in cortex that were subsequently reconstructed through serial sections. A total of 36 complete axons and 166 axon segments were reconstructed. Our results identified at least 2 main subpopulations of K axons in macaque V1 based on branching patterns and bouton distribution. Axons that arise primarily from LGN layers K1 and K2 are morphologically simple and tend to branch in cortical layers 1 and 3A. These axons give rise to fewer boutons than seen in axons arising from the dorsal K LGN layers K3-K6. Axons that arise from LGN layers K3-K6 terminate as complex, focused arbors in the cytochrome oxidase (CO) blobs in layer 3Balpha, with only occasional simple projections to the more superficial layers of cortex. Combined with previous observations, our data suggest that there are at least 3 subclasses of K LGN axons in macaque monkey that are similar to K axons identified earlier in both nocturnal simian owl monkeys (Ding and Casagrande 1997) and in prosimian, bush babies (Lachica and Casagrande 1992) suggesting that the LGN K channels that terminate in the CO blobs and in layer 1 are not unique to macaque monkeys but are a common primate feature.     

The pyramidal cell of the sensorimotor cortex of the macaque monkey: phenotypic variation

Recent studies have revealed striking differences in pyramidal cell structure among cortical regions involved in the processing of different functional modalities. For example, cells involved in visual processing show systematic variation, increasing in morphological complexity with rostral progression from V1 through extrastriate areas. Differences have also been identified between pyramidal cells in somatosensory, motor and prefrontal cortex, but the extent to which the pyramidal cell phenotype may vary between these functionally related cortical regions remains unknown. In the present study we investigated the structure of layer III pyramidal cells in somatosensory and motor areas 3b, 4, 5, 6 and 7b of the macaque monkey. Cells were intracellularly injected in fixed, flat-mounted cortical slices and analysed for morphometric parameters. The size of the basal dendritic arbours, the number of their branches and their spine density were found to vary systematically between areas. Namely, we found a trend for increasing complexity in dendritic arbour structure through areas 3b, 5 and 7b. A similar trend occurred through areas 4 and 6. The differences in arbour structure may determine the number of inputs received by neurons and may thus be an important factor in determining function at the cellular and systems level.     

A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.     

Transient and permanent deficits in motion perception after lesions of cortical areas MT and MST in the macaque monkey

We examined the nature and the selectivity of the motion deficitsproduced by lesions of extrastriate areas MT and MST. Lesionswere made by injecting ibotenic acid into the representationof the left visual field in two macaque monkeys. The monkeysdiscriminated two stimuli that differed either in stimulus directionor orientation. Direction and orientation discrimination wereassessed by measuring thresholds with gratings and random-dotsplaced in the intact or lesioned visual fields. At the startof behavioral testing, we found pronounced, motion-specificdeficits in thresholds for all types of moving stimuli, includingpronounced elevations in contrast thresholds and in signal-to-noisethresholds measured with moving gratings, as well as deficitsin direction range thresholds and motion coherence measuredwith random-dot stimuli. In addition, the accuracy of directiondiscrimination was reduced at smaller spatial displacements(i.e. step sizes), suggesting an increase in spatial scale ofthe residual directional mechanism. Subsequent improve- mentsin thresholds were seen with all motion stimuli, as behavioraltraining progressed, and these improvements occurred only withextensive behavioral testing in the lesioned visual field. Theseimprovements were particularly pronounced for stimuli not maskedby noise. On the other hand, deficits in the ability to extractmotion from noisy stimuli and in the accuracy of direction discriminationpersisted despite extensive behavioral training. These resultsdemonstrate the importance of areas MT and MST for the perceptionof motion direction, particularly in the presence of noise.In addition, they provide evidence for the importance of behavioraltraining for functional recovery after cortical lesions. Thedata also strongly support the idea of functional specializationof areas MT and MST for motion processing.     

Organization of nonprimary motor cortical inputs on pyramidal and nonpyramidal tract neurons of primary motor cortex: An electrophysiological study in the macaque monkey

To elucidate the functions of nonprimary motor cortical (nPMC) areas whose afferents synapse onto output neurons of the primary motor cortex (PMC), we examined the responses of pyramidal tract neurons (PTNs) and non-PTNs (nPTNs) to electrical stimulation in the three nPMCs, the supplementary motor area (SMA) and the dorsal and ventral divisions of the premotor cortex (PMd and PMv), with extracellular unit recording in alert monkeys. Typical responses of PTNs to nPMC stimulation were early orthodromic excitatory responses followed by inhibitory responses. Among 27 PTNs tested by constructing peri-stimulus time histograms, 19 (70.4%) showed inhibitory responses to stimulation in all of the nPMC areas. In contrast, 5/33 PTNs (15.2%) and 10/72 nPTNs (13.9%) showed excitatory responses to stimulation in all of the nPMCs. The inhibitory responses of PTNs were mediated by inhibitory interneurons, some of which may correspond to nPTNs in the superficial layers of the PMC. These interneurons probably possess widely extended axons and nonspecifically inhibit multiple PTNs in layer V. The excitatory and inhibitory influences, and the patterns of convergence of inputs from the nPMCs onto the PTNs, are important to understand motor control by the nPMC-PMC-spinal cord pathway.     

The global pattern of cytochrome oxidase stripes in visual area V2 of the macaque monkey

In primate visual area V2, histochemical staining for cytochrome oxidase (CO) reveals a tripartite pattern of densely labeled thick and thin stripes separated by pale interstripes. This modularity is believed to be related to functionally distinct processing streams that course through the hierarchy of visual areas. Here, we studied the overall pattern of CO stripes in V2 of the macaque monkey, using tissue that had been physically unfolded and flattened prior to histological sectioning. CO stripes were identified on the basis of their physical dimensions and on their differential immunoreactivity for the monoclonal antibody Cat-301. We observed several distinctive features of compartmental organization in V2. The most prominent was a dorso- ventral asymmetry in the stripe pattern, occurring in the majority of cases studied. In dorsal V2, most stripes measure approximately 10 mm in length and run roughly orthogonal to both the posterior and anterior borders of V2. In contrast, many stripes in ventral V2 have a curved or oblique trajectory, and some extend up to 20 mm in length. Stripes following a curved trajectory often become nearly parallel to the anterior border of V2. These differences imply an asymmetry in how the visual field maps onto dorsal versus ventral stripes. Occasionally, thin stripes fail to alternate with thick stripes but instead occur next to one other, separated only by interstripes. In three most complete reconstructions, we found that unfolded V2 is approximately 110 mm in length, approximately 900 mm2 in surface area, and that it contains approximately 28 complete sets of stripes (one thick, one thin and two interstripes), yielding an average of approximately 4 mm per set of stripes. The maximum width of ventral V2 (13-14 mm) exceeds that of dorsal V2 (10 mm), and there is a consistent narrowing of V2 in the region of foveal representation (3-5 mm).      

Inhibitory synapse cover on the somata of excitatory neurons in macaque monkey visual cortex

Electron microscopy was used in macaque monkey cortical area V1 to investigate what factors might determine the proportion of somatic membrane covered by inhibitory type 2 synapses. In a sample of 4654 excitatory neurons, synapse cover did not correlate consistently with cell variety (pyramid or spiny stellate), soma size, synaptic apposition length or thalamic input. There were significant differences in somatic synapse cover per layer, but the pattern of differences in cover among layers differed significantly between animals, suggesting that laminar environment alone is not a generally applicable determinant of amount of inhibitory synapse cover. The pattern of cover for cells in different layers was, however, similar between the two hemispheres of an individual monkey. Measures of inhibitory synapse cover on four sets of pyramidal neurons in layers 5 and 6, each with different efferent projection targets, showed that the sets differed significantly from other cells in their respective layers, and differed significantly from each other. These findings demonstrate that there is unique circuitry for different subsystems within single layers of cortex and provide a rationale for the rich variety of cortical GABAergic interneurons within single layers.     

The multiple roles of visual cortical areas MT/MST in remembering the direction of visual motion

Although the role of cortical areas MT and MST (MT/MST) in the processing of directional motion information is well established, little is known about the way these areas contribute to the execution of complex behavioral tasks requiring the use of such information. We tested monkeys with unilateral lesions of these areas on a visual working memory task in which motion signals not only had to be encoded, but also stored for brief periods of time and then retrieved. The monkeys compared the directions of motion of two random-dot stimuli, sample and test, separated by a temporal delay. By increasing the temporal delay and spatially separating the two stimuli, placing one in the affected visual field and the other in the intact visual field, we were able to assess the contribution of MT/MST to specific components of the task: encoding (sample), retention (delay) and encoding/retrieval/comparison (test). We found that the effects of MT/MST lesions on specific components depended upon the demands of the task and the nature of the visual motion stimuli. Whenever stimuli consisted of random dots moving in a broad range of directions, MT/MST lesions appeared to affect encoding. Furthermore, when the lesions affected encoding of the sample, retention of the direction of stimulus motion was also affected. However, when the stimulus was coherent and the emphasis of the task was on the comparison of small direction differences, the absence of MT/MST had major impact on the retrieval/comparison component of the task and not on encoding or storage.     

The effects of aging on layer 1 of primary visual cortex in the rhesus monkey

The effect of age on layer 1 in primary visual cortex was determined in 19 rhesus monkeys of various ages. Twelve of the monkeys had been behaviorally tested. With age layer 1 becomes thinner and the glial limiting membrane becomes thicker. In the neuropil of layer 1 many of the dendrites in old monkeys appear to be degenerating and, as a consequence, electron micrographs from old monkeys display fewer dendritic and spine profiles per unit area than in young monkeys. As determined using both the disector and size-frequency methods, there is also a concomitant decrease in the numerical density of synapses with age. Although there is a significant correlation between the thinning of layer 1 in area 17 and age, there is no significant correlation between either the thinning of layer 1 or its loss of synapses and any of the behavioral measures of memory function obtained from the 12 behaviorally tested monkeys. Similar morphological changes with age occur in layer 1 of prefrontal cortex of these same monkeys, but in area 46 both the thinning of layer 1 and the loss of synapses show a significant correlation with behavioral measures of memory function. These differences between layer 1 in these two cortical areas presumably relate to the fact that prefrontal cortex has a greater role in subserving cognition than does primary visual cortex.     

Organization of horizontal axons in the inferior temporal cortex and primary visual cortex of the macaque monkey

We investigated the organization of horizontal connections at two distinct hierarchical levels in the ventral visual cortical pathway of the monkey, the inferior temporal (TE) and primary visual (V1) cortices. After injections of anterograde tracers into layers 2 and 3, clusters of terminals ('patches') of labeled horizontal collaterals in TE appeared at various distances up to 8 mm from the injection site, while in V1 clear patches were distributed only within 2 mm. The size and spacing of these patches in TE were larger and more irregular than those observed in V1. The labeling intensity of patches in V1 declined sharply with distance from the injection site. This tendency was less obvious in TE; a number of densely labeled patches existed at distant sites beyond weakly labeled patches. While injections into both areas resulted in an elongated pattern of patches, the anisotropy was greater in TE than in V1 for injections of a similar size. Dual tracer injections and larger-sized injections further revealed that the adjacent sites in TE had spatially distinct horizontal projections, compared to those in V1. These area-specific characteristics of the horizontal connections may contribute to the differences in visual information processing of TE and V1.     

The effects of morphine self-administration on cortical pyramidal cell structure in addiction-prone lewis rats

The consumption of drugs of abuse provokes sensitization, the development of tolerance, dependency, and eventually addiction. It is thought that these events are partially a consequence of drug-induced alterations in the organization of neuronal circuits in specific areas of the brain. In the present study, we have used intracellular injections of lucifer yellow to examine the alterations that may occur in cortical pyramidal neurons of addiction-prone Lewis rats following 15 days of self-administration of morphine. Specifically, the effects of morphine on the structure, size and branching complexity of the basal dendrites, and spine density were determined in the basal dendritic arbors of layer III pyramidal neurons in both the prelimbic and motor cortex. We found that following morphine self-administration, there was a reduction in the size and branching complexity of the dendritic arbors of pyramidal cells in the motor cortex. In contrast, prelimbic pyramidal neurons from these morphine-treated animals had larger and longer basal dendritic arbors. Furthermore, the spine density on pyramidal neurons was higher in both cortical regions of morphine self-administered rats. These results suggest that at least part of the behavioral changes produced by repeated opiate administration may be attributed to alterations in pyramidal cell structure.     

The organization of pyramidal cells in area 18 of the rhesus monkey

The aim of this study was to investigate the vertical organization of axons and pyramidal cells in area 18, and to compare it with that in area 17. In area 18 there are regularly spaced vertical bundles of myelinated axons that have an average center-to-center spacing of 21 microns. This arrangement of axons resembles that in area 17. Pyramidal cells in area 18 and their apical dendrites are less regularly arranged. The apical dendrites of the pyramidal cells of layer 6A aggregate with those from layer 5 pyramids to form swathes of apical dendrites that pass into layer 4. There they are joined by the apical dendrites of the small layer 4 pyramids, so that much of the neuropil of layer 4 is occupied by apical dendrites. Most of these apical dendrites form their terminal tufts in layer 3. Very few of them reach layer 1, which is dominated by the apical dendrites of layer 2/3 pyramids. Thus, there are two tiers of apical dendrites and their apical tufts, a deep one formed by the layer 4, 5 and 6 apical dendrites that terminate in layer 3, and a second one formed by the apical dendrites of layer 2/3 pyramids that terminate in layer 1. In contrast, in area 17 the apical dendrites of layer 5 pyramids form discrete clusters that have a center-to-center spacing of 23 microns. These clusters are joined by the apical dendrites of the layer 2/3 pyramids and all of these apical dendrites form their apical tufts in layer 1. Based upon the dispositions of the apical dendrites of the pyramidal cells in area 17 and 18, we speculate that the influences of, and the interactions between, the feed-forward and feed-back signals in the two areas are quite different, because in the two areas different postsynaptic targets are available to these afferents.      

The connections of layer 4 subdivisions in the primary visual cortex (V1) of the owl monkey

The primary visual cortex (V1) of primates receives signals from parallel lateral geniculate nucleus (LGN) channels. These signals are utilized by the laminar and compartmental [i.e. cytochrome oxidase (CO) blob and interblob] circuitry of V1 to synthesize new output pathways appropriate for the next steps of analysis. Within this framework, this study had two objectives: (i) to analyze the con- nections between primary input and output layers and compartments of V1; and (ii) to determine differences in connection patterns that might be related to species differences in physiological properties in an effort to link specific pathways to visual functions. In this study we examined the intrinsic interlaminar connections of V1 in the owl monkey, a nocturnal New World monkey, with a special emphasis on the projections from layer 4 to layer 3. Interlaminar connections were labeled via small iontophoretic or pressure injections of tracers [horseradish peroxidase, biocytin, biotinylated dextrine amine (BDA) or cholera toxin subunit B conjugated to colloidal gold particles]. Our most significant finding was that layer 4 (4C of Brodmann) can be divided into three tiers based upon projections to the superficial layers. Specifically, we find that 4alpha (4Calpha), 4beta (4Cbeta) and 4ctr send primary projections to layers 3C (4B), 3Bbeta (4A) and 3Balpha (3B), respectively. Examination of laminar structure with Nissl staining supports a tripartite organization of layer 4. The cortical output layer above layer 3Balpha (3B) (e.g. layer 3A) does not appear to receive any direct connections from layer 4 but receives heavy input from layers 3Balpha (3B) and 3C (4B). Some connectional differences also were observed between the subdivisions of layer 3 and the infragranular layers. No consistent differences in connections were observed that distinguished CO blobs from interblobs or that could be correlated with differences in visual lifestyle (nocturnal versus diurnal) when compared with connectional data in other primates. Re-examination of data from previous studies in squirrel and macaque monkeys suggests that the tripartite organization of layer 4 and the unique projection pattern of layer 4ctr are not restricted to owl monkeys, but are common to a number of primate species.     

Separate processing dynamics for texture elements, boundaries and surfaces in primary visual cortex of the macaque monkey.

A visual scene is rapidly segmented into the regions that are occupied by different objects and background. Segmentation may be initiated from the detection of boundaries, followed by the filling-in of the surfaces between these boundaries to render them visible. Alternatively, segmentation may be based on grouping of surface elements that are similar, so that boundaries are (implicitly) identified as the borders between elements that are grouped into objects. Here, we present recordings from awake monkey primary visual cortex that show that in late (>80 ms) components of the neural responses a correlate of boundary formation is expressed, followed by a filling-in (also called colouring) between the edges. These data favour a model of segmentation where boundary formation initiates surface filling-in.     

Reentry and the problem of integrating multiple cortical areas: simulation of dynamic integration in the visual system.

Studies of the cerebral cortex, particularly those of the visual system, demonstrate the existence of multiple, anatomically segregated and functionally specialized cortical areas. There is no evidence that these areas, which are linked by a network of reciprocal connections, are coordinated by a higher-order center. The visual image that we perceive, however, seems to be unified and coherent. In this article, we address the problem of integration posed by these observations. In an extension of our previous work, we develop a dynamic model of reentry. Reentry is a process of parallel and recursive signaling along ordered anatomical connections that achieves integration by giving rise to constructive and correlative properties within and among maps. We present and test a computer model simulating nine functionally segregated visual areas organized into three streams for form, color, and motion. The model receives visual input consisting of camera images of objects of different shapes and colors. We show the specialized response properties of the areas in the three streams. A computational strategy involving a phase variable is introduced to represent explicitly the dynamics of short-term temporal correlations among thousands of units distributed across different areas. We then illustrate constructive and correlative consequences of reentry within a system of reciprocal intra- and interareal connections by two examples taken from psychophysics: generation of form from motion and motion capture. The model solves the so-called "binding problem" through short-term correlations, which serve to link similar object features within a simulated cortical area and to bind multiple attributes of one or more objects across several areas, including a nontopographic one. Integration emerges from cooperative effects within and among the specialized areas. These effects lead to a simple output, a simulated foveation response, that is used as a basis for conditioning. Reward is mediated by the activation of a saliency system that is modeled on diffuse projection systems in the brain. As a result, the visual cortical model carries out foveation responses to input stimuli that require the dynamic conjunction and discrimination of form, color, and location for successful performance.     

Single cell integration of animate form, motion and location in the superior temporal cortex of the macaque monkey

This study investigated the cellular mechanisms in the anterior part of the superior temporal sulcus (STSa) that underlie the integration of different features of the same visually perceived animate object. Three visual features were systematically manipulated: form, motion and location. In 58% of a population of cells selectively responsive to the sight of a walking agent, the location of the agent significantly influenced the cell's response. The influence of position was often evident in intricate two- and three-way interactions with the factors form and/or motion. For only one of the 31 cells tested, the response could be explained by just a single factor. For all other cells at least two factors, and for half of the cells (52%) all three factors, played a significant role in controlling responses. Our findings support a reformulation of the Ungerleider and Mishkin model, which envisages a subdivision of the visual processing into a ventral 'what' and a dorsal 'where' stream. We demonstrated that at least part of the temporal cortex ('what' stream) makes ample use of visual spatial information. Our findings open up the prospect of a much more elaborate integration of visual properties of animate objects at the single cell level. Such integration may support the comprehension of animals and their actions.     

Dual role of substance P/GABA axons in cortical neurotransmission: synaptic triads on pyramidal cell spines and basket-like innervation of layer II-III calbindin interneurons in primate prefrontal cortex

In spite of accumulating evidence on the potent neuromodulatory, neuroprotective, trophic and memory-enhancing effects of the neuropeptide substance P (SP) in the cerebral cortex, the excitatory or inhibitory nature of the cortical SP innervation remains unclear and the postsynaptic targets of SP fibers are not defined. To obtain further insight into these issues, we have examined SP-containing axons and their postsynaptic targets in the prefrontal cortex of adult monkeys with single- and double label immunocytochemistry combined with light and correlated electron microscopy. SP fibers in the primate prefrontal cortex, unlike those in the rat cortex, preferentially innervate cortical layers I, II and upper layer III. Our results demonstrate for the first time that all SP-immunoreactive boutons in all cortical layers contain GABA. Of the entire sample of SP boutons, 53% synapse on dendritic shafts, 39% on dendritic spines and 8% on cell bodies. Another new finding is that synapse-forming SP boutons, in addition to their known innervation of pyramidal cells, form pericellular baskets around interneurons in layers II and upper III, a subpopulation of which contains calbindin D28k. Finally, the study also revealed that SP boutons frequently participate in 'synaptic triads' with spines which receive another (asymmetric, putatively excitatory amino acid-utilizing) synapse. Our findings indicate that SP/GABA axons in the primate prefrontal cortex modulate excitatory amino acid- mediated neurotransmission and control feed-forward disinhibitory GABAergic circuits in supragranular cortical layers.      

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.