Modular Organization of Signal Transmission in Primate Somatosensory Cortex.

Axonal patches are known as the major sites of synaptic connections in the cerebral cortex of higher order mammals. However, the functional role of these patches is highly debated. Patches are formed by populations of nearby neurons in a topographic manner and are recognized as the termination fields of long-distance lateral connections within and between cortical areas. In addition, axons form numerous boutons that lie outside the patches, whose function is also unknown. To better understand the functional roles of these two distinct populations of boutons, we compared individual and collective morphological features of axons within and outside the patches of intra-areal, feedforward, and feedback pathways by way of tract tracing in the somatosensory cortex of New World monkeys. We found that, with the exception of tortuosity, which is an invariant property, bouton spacing and axonal convergence properties differ significantly between axons within patch and no-patch domains. Principal component analyses corroborated the clustering of axons according to patch formation without any additional effect by the type of pathway or laminar distribution. Stepwise logistic regression identified convergence and bouton density as the best predictors of patch formation. These findings support that patches are specific sites of axonal convergence that promote the synchronous activity of neuronal populations. On the other hand, no-patch domains could form a neuroanatomical substrate to diversify the responses of cortical neurons.

Acute blockade of NR2C/D subunit-containing N-methyl-D-aspartate receptors modifies sleep and neural oscillations in mice.

N-methyl-d-aspartate receptors (NMDARs) play an important role in excitatory neurotransmission and have been associated with psychiatric conditions including schizophrenia and major depressive disorder. NMDARs are composed of two NR1 and two NR2 subunits. The type of NR2 subunit determines electrophysiological and pharmacological properties of the receptor. As the precise role of NR2C/D subunit-containing NMDARs is poorly understood in vivo, we have performed behavioural, quantitative electroencephalographic (qEEG) and polysomnographic analysis following acute pharmacological blockade of these receptor subtypes in adult male CD1 mice. We found that NR2C/D blockade impaired motor coordination and decreased the amount of gross movement. Moreover, EEG power in multiple frequency bands including theta and sigma were found to decrease significantly together with a decrease of theta oscillation frequency. Changes of these qEEG measures were accompanied by a decrease in time spent in slow-wave and rapid eye movement sleep, but an increase of time spent in quiet wakefulness. Furthermore, there was a significant decrease of sleep spindle oscillation density. These findings highlight the importance of NR2C/D-containing NMDARs and take a step towards establishing a link between electrophysiological correlates of psychiatric disorders and underlying synaptic dysfunctions.

Synaptic organization of cortico-cortical communication in primates.

In cortical circuitry, synaptic communication across areas is based on two types of axon terminals, small and large, with modulatory and driving roles, respectively. In contrast, it is not known whether similar synaptic specializations exist for intra-areal projections. Using anterograde tracing and three-dimensional reconstruction by electron microscopy (3D-EM), we asked whether large boutons form synapses in the circuit of somatosensory cortical areas 3b and 1. In contrast to observations in macaque visual cortex, light microscopy showed both small and large boutons not only in inter-areal pathways, but also in long-distance intrinsic connections. 3D-EM showed that correlation of surface and volume provides a powerful tool for classifying cortical endings. Principal component analysis supported this observation and highlighted the significance of the size of mitochondria as a distinguishing feature of bouton type. The larger mitochondrion and higher degree of perforated postsynaptic density associated with large rather than to small boutons support the driver-like function of large boutons. In contrast to bouton size and complexity, the size of the postsynaptic density appeared invariant across the bouton types. Comparative studies in human supported that size is a major distinguishing factor of bouton type in the cerebral cortex. In conclusion, the driver-like function of the large endings could facilitate fast dissemination of tactile information within the intrinsic and inter-areal circuitry of areas 3b and 1.

Corrigendum to "Structural correlates of modular organization of activity propagation in the primate somatosensory cortex" [IBROR 6S (2019) S540].

[This corrects the article DOI: 10.1016/j.ibror.2019.07.1681.].

Strategic Positioning of Connexin36 Gap Junctions Across Human Retinal Ganglion Cell Dendritic Arbors.

Connexin36 (Cx36) subunits form gap junctions (GJ) between neurons throughout the central nervous system. Such GJs of the mammalian retina serve the transmission, averaging and correlation of signals prior to conveying visual information to the brain. Retinal GJs have been exhaustively studied in various animal species, however, there is still a perplexing paucity of information regarding the presence and function of human retinal GJs. Particularly little is known about GJ formation of human retinal ganglion cells (hRGCs) due to the limited number of suitable experimental approaches. Compared to the neuronal coupling studies in animal models, where GJ permeable tracer injection is the gold standard method, the post-mortem nature of scarcely available human retinal samples leaves immunohistochemistry as a sole approach to obtain information on hRGC GJs. In this study Lucifer Yellow (LY) dye injections and Cx36 immunohistochemistry were performed in fixed short-post-mortem samples to stain hRGCs with complete dendritic arbors and locate dendritic Cx36 GJs. Subsequent neuronal reconstructions and morphometric analyses revealed that Cx36 plaques had a clear tendency to form clusters and particularly favored terminal dendritic segments.

[Neuronal connections within the hand representation in areas 3b and 1 of the somatosensory cortex in primates]. / Neuronalis összeköttetések a szomatoszenzoros kérgi área 3b és área 1 kézreprezentációs területén foemlosökben.

INTRODUCTION: The close functional relationship between areas 3b and 1 of the somatosensory cortex is based on their reciprocal connections indicating that tactile sensation depends on the interaction of these two areas. AIM: The aim of the authors was to explore this neuronal circuit at the level of the distal finger pad representation. METHOD: The study was made by bidirectional tract tracing aided by neurophysiological mapping in squirrel monkeys (Saimiri sciureus). RESULTS: Inter-areal connections between the two areas preferred the homologues representations. However, intra-areal connections were formed between the neighboring finger pad representations supporting the physiological observations. Interestingly, the size of the local input area of the injected cortical micro-region, which differed in the two areas, represented the same skin area. CONCLUSIONS: The authors propose that intra-areal connections are important in integrating information across fingers, while inter-areal connections are important in maintaining input localization during hand movement. Orv. Hetil., 2016, 157(33), 1320-1325.

Characterization of connexin36 gap junctions in the human outer retina.

Retinal connexins (Cx) form gap junctions (GJ) in key circuits that transmit average or synchronize signals. Expression of Cx36, -45, -50 and -57 have been described in many species but there is still a disconcerting paucity of information regarding the Cx makeup of human retinal GJs. We used well-preserved human postmortem samples to characterize Cx36 GJ constituent circuits of the outer plexiform layer (OPL). Based on their location, morphometric characteristics and co-localizations with outer retinal neuronal markers, we distinguished four populations of Cx36 plaques in the human OPL. Three of these were comprised of loosely scattered Cx36 plaques; the distalmost population 1 formed cone-to-rod GJs, population 2 in the mid-OPL formed cone-to-cone GJs, whereas the proximalmost population 4 likely connected bipolar cell dendrites. The fourth population (population 3) of Cx36 plaques conglomerated beneath cone pedicles and connected dendritic tips of bipolar cells that shared a common presynaptic cone. Overall, we show that the human outer retina displays a diverse cohort of Cx36 GJ that follows the general mammalian scheme and display a great functional diversity.

Stratified organization and disorganization of inner plexiform layer revealed by TNAP activity in healthy and diabetic rat retina.

Tissue non-specific alkaline phosphatase (TNAP), an abundant ectophosphatase, is present in various organs including the brain and retina of several vertebrate species. Evidence is emerging that TNAP influences neural functions in multiple ways. In rat, strong TNAP activity has been found in retinal vessels, photoreceptors, and both synaptic layers. In the present study, we identified eleven strata of the inner plexiform layer (IPL) by using TNAP histochemistry alone. The TNAP strata corresponded exactly to the strata seen after combined immunohistochemistry with four canonical IPL markers (TH-ChAT-CR-PKCα). Therefore, as described in other mammalian species, our data support the existence of multiple morphologically and functionally discernible IPL strata in rats. Remarkably, the stratification pattern of the IPL was severely disrupted in a diabetic rat model, even before changes in the canonical IPL markers were detectable. These findings indicate that TNAP histochemistry offers a more straightforward, but also more sensitive, method for investigating retinal strata and their diabetes-induced degeneration.

Connectivity of somatosensory cortical area 1 forms an anatomical substrate for the emergence of multifinger receptive fields and complex feature selectivity in the squirrel monkey (Saimiri sciureus).

Converging evidence shows that interaction of digit-specific input, which is required to form global tactile percepts, begins as early as area 3b in the primary somatosensory cortex with the involvement of intrinsic lateral connections. How tactile processing is further elaborated in area 1, the next stage of the somatosensory cortical hierarchy, is less understood. This question was investigated by studying the tangential distribution of intrinsic and interareal connections of finger representations of area 1. Retrogradely labeled cell densities and anterogradely labeled fibers and terminal patches were plotted and quantified with respect to the hand representation by combining tract tracing with electrophysiological mapping and intrinsic signal optical imaging in somatosensory areas. Intrinsic connections of distal finger pad representations of area 1 spanned the representation of multiple digits indicating strong cross-digit connectivity. Area 1 distal finger pad regions also established high-density connections with homotopic regions of areas 3b and 2. Although similar to area 3b, connections of area 1 distributed more widely and covered a larger somatotopic representation including more proximal parts of the finger representations. The lateral connectivity pattern of area 1 is a suitable anatomical substrate of the emergence of multifinger receptive fields, complex feature selectivity, and invariant stimulus properties of the neurons.

Intrinsic horizontal connections process global tactile features in the primary somatosensory cortex: neuroanatomical evidence.

To understand manual tactile functions in primates, it is essential to explore the interactions between the finger pad representations in somatosensory cortex. To this end, we used optical imaging and electrophysiological mapping to guide neuroanatomical tracer injections into distal digit tip representations of Brodmann area 3b in the squirrel monkey. Retrogradely labeled cell densities and anterogradely labeled fibers and terminal patches in somatosensory areas were plotted and quantified with respect to tangential distribution. Within area 3b, reciprocal patchy distribution of anterograde and retrograde labeling spanned the representation of the distal pad of multiple digits, indicating strong cross-digit connectivity. Inter-areal connections revealed bundles of long-range fibers projecting anteroposteriorly, connecting area 3b with clusters of labeled neurons and terminal axon arborizations in area 1. Inter-areal linkage appeared to be largely confined to the representation of the injected finger. These findings provide the neuroanatomical basis for the interaction between distal finger pad representations observed by recent electrophysiological studies. We propose that intra-areal connectivity may be heavily involved in interdigit integration such as shape discrimination, whereas long-range inter-areal connections may subserve active touch in a digit-specific manner.