Dendritic Bundles, Minicolumns, Columns, and Cortical Output Units

The search for the fundamental building block of the cerebral cortex has highlighted three structures, perpendicular to the cortical surface: (i) columns of neurons with radially invariant response properties, e.g., receptive field position, sensory modality, stimulus orientation or direction, frequency tuning etc., (ii) minicolumns of radially aligned cell bodies and (iii) bundles, constituted by the apical dendrites of pyramidal neurons with cell bodies in different layers. The latter were described in detail, and sometimes quantitatively, in several species and areas. It was recently suggested that the dendritic bundles consist of apical dendrites belonging to neurons projecting their axons to specific targets. We review the concept above and suggest that another structural and computational unit of cerebral cortex is the cortical output unit, i.e., an assembly of bundles of apical dendrites and their parent cell bodies including each of the outputs to distant cortical or subcortical structures, of a given cortical locus (area or part of an area). This somato-dendritic assembly receives inputs some of which are common to the whole assembly and determine its radially invariant response properties, others are specific to one or more dendritic bundles, and determine the specific response signature of neurons in the different cortical layers and projecting to different targets

Specificity of Neuronal Responses in Primary Visual Cortex Is Modulated by Interhemispheric CorticoCortical Input

Within the visual cortex, it has been proposed that interhemispheric interactions serve to re-establish the continuity of the visual field across its vertical meridian (VM) by mechanisms similar to those used by intrinsic connections within a hemisphere. However, other specific functions of transcallosal projections have also been proposed, including contributing to disparity tuning and depth perception. Here, we consider whether interhemispheric connections modulate specific response properties, orientation and direction selectivity, of neurons in areas 17 and 18 of the ferret by combining reversible thermal deactivation in one hemisphere with optical imaging of intrinsic signals and single-cell electrophysiology in the other hemisphere. We found interhemispheric influences on both the strength and specificity of the responses to stimulus orientation and direction of motion, predominantly at the VM. However, neurons and domains preferring cardinal contours, in particular vertical contours, seem to receive stronger interhemispheric input than others. This finding is compatible with interhemispheric connections being involved in horizontal disparity tuning. In conclusion, our results support the view that interhemispheric interactions mainly perform integrative functions similar to those of connections intrinsic to one hemisphere

The crossed projection to the striatum in two species of monkey and in humans: behavioral and evolutionary significance

The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species

Editorial Physiology and Plasticity of Interhemispheric Connections

The corpus callosum (CC for aficionados) is the largest fiber bundle in the brain and establishes connections between the hemispheres, and predominantly, but not solely, between the cortical areas. Functionally mysterious for a long time, it shared with the pineal gland the honor of being considered the site of the soul M. Fabri and G. Polonara provide a functional map of callosal topography by charting the BOLD signal evoked in callosal axons by taste, tactile, auditory, and visual stimuli and by motor tasks. This approach is at the frontier of what is usually obtained from BOLD signals. It provides results that are compatible with what is predicted by anatomy in the case of axons originating from primary areas, but it also shows activations that could not have been predicted from anatomy, probably due to axons originating in multisensory areas. K. E. Schmidt finds that, in the visual cortex, CC connections have a multiplicative shift of the responses and this is an interesting finding that goes beyond the old debate of whether callosal connections are excitatory or inhibitory. The finding is placed within the frame of the historical question of the general nature of callosal connections. Hubel and Wiesel V. Beaulé et al. focus on the role of CC connections in disentangling bilateral manual movements. From juvenile, to adult, to pathological conditions, the degrees of manual independence are differently modulated and this may be due to inhibitory action of callosal connections. Interestingly, inhibition between the hemispheres has been repeatedly reported for the motor functions, particularly in 2 Neural Plasticity man, although it has been observed in the visual cortex as well, where it seems to be quickly overridden by the excitatory interactions Over the last 30 years, developmental work on the CC has focused on three main themes: (i) the molecular mechanisms of axonal guidance between the hemispheres, (ii) the establishment of topographical connections, and (iii) the role of activity in the development of the connections. M. Nishikimi et al. review the first of the above themes, with special attention to the midline structures and neighboring axons. They also describe alterations in these navigational mechanisms that result in callosal dysgenesis in humans and mice. Y. Tagawa and T. Hirano review the last of the above issues and provide information on the molecular mechanisms by which spontaneous activity sculpts callosal projections. They conclude that both presynaptic and postsynaptic neuronal activities are critically involved in callosal axon development, and discuss the intracellular signaling pathways that work downstream of neuronal firing. It may be added that the overproduction and elimination of axons in development are central to the second of the themes above and continue to provide testable hypotheses on the nature of developmental plasticity of cortical connectivity Noninvasive structural and functional imaging techniques are taking an increasingly large share of brain studies, but this raises the question of how novel and more traditional, firmly established methodologies map onto each other. The CC is practically unavoidable in non-invasive structural studies, and, therefore, it can provide some general answers because of its central position in the brain, its relative &quot;simplicity&quot; and the amount of anatomical and functional information available. J. F. Olavarria et al. relate the critical period of callosal development, as defined by the reorganization of visual callosal connections caused by early enucleation, to the development of water diffusion parameters. This is important new information that complements the view that callosal plasticity relates to axonal maturation and differentiation. M. G. Knyazeva places callosal maturation as estimated by MRI and coherence EEG analysis, within the context of excitatory and inhibitory interactions between the hemispheres. P. Mathew et al. report data in preterm infants showing a relation between motor-specific scores and fractional anisotropy of anterior midbody of CC, the region where axons interconnecting motor areas course. Finally N. Takeuchi et al. introduce the concept of adult CC plasticity that might be elicited by trans-cranial stimulation in humans. They also discuss the use of brain stimulation techniques as a possible rehabilitation strategy to reinstate interhemispheric balance in patients with stroke

Diversity of cortico-descending projections: histological and diffusion MRI characterization in the monkey

The axonal composition of cortical projections originating in premotor, supplementary motor (SMA), primary motor (a4), somatosensory and parietal areas and descending towards the brain stem and spinal cord was characterized in the monkey with histological tract tracing, electron microscopy (EM) and diffusion MRI (dMRI). These 3 approaches provided complementary information. Histology provided accurate assessment of axonal diameters and size of synaptic boutons. dMRI revealed the topography of the projections (tractography), notably in the internal capsule. From measurements of axon diameters axonal conduction velocities were computed. Each area communicates with different diameter axons and this generates a hierarchy of conduction delays in this order: a4 (the shortest), SMA, premotor (F7), parietal, somatosensory, premotor F4 (the longest). We provide new interpretations for i) the well-known different anatomical and electrophysiological estimates of conduction velocity; ii) why conduction delays are probably an essential component of the cortical motor command; and iii) how histological and dMRI tractography can be integrated

The complex hodological architecture of the macaque dorsal intraparietal areas as emerging from neural tracers and DW-MRI tractography

In macaque monkeys, dorsal intraparietal areas are involved in several daily visuo-motor actions. However, their border and sources of cortical afferents remain loosely defined. Combining retrograde histological tracing and MRI diffusion-based tractography we found a complex hodology of the dorsal bank of the IPS, which can be subdivided into a rostral area PEip, projecting to the spinal cord, and a caudal area MIP lacking such projections. Both include a rostral and a caudal sector, emerging from their ipsilateral, gradient-like connectivity profiles. As tractography estimations, we used the cross-sectional volume of the white matter bundles connecting each area with other parietal and frontal regions, after selecting ROIs corresponding to the injection sites of neural tracers. For most connections, we found a significant correlation between the proportions of cells projecting to all sectors of PEip and MIP along the continuum of the dorsal bank of the IPS and tractography. The latter also revealed “false positive” but plausible streamlines awaiting histological validation

Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1

Class I phosphoinositide 3-kinases (PI3Ks) are implicated in many cellular responses controlled by receptor tyrosine kinases (RTKs), including actin cytoskeletal remodeling. Within this pathway, Rac is a key downstream target/effector of PI3K. However, how the signal is routed from PI3K to Rac is unclear. One possible candidate for this function is the Rac-activating complex Eps8–Abi1–Sos-1, which possesses Rac-specific guanine nucleotide exchange factor (GEF) activity. Here, we show that Abi1 (also known as E3b1) recruits PI3K, via p85, into a multimolecular signaling complex that includes Eps8 and Sos-1. The recruitment of p85 to the Eps8–Abi1–Sos-1 complex and phosphatidylinositol 3, 4, 5 phosphate (PIP3), the catalytic product of PI3K, concur to unmask its Rac-GEF activity in vitro. Moreover, they are indispensable for the activation of Rac and Rac-dependent actin remodeling in vivo. On growth factor stimulation, endogenous p85 and Abi1 consistently colocalize into membrane ruffles, and cells lacking p85 fail to support Abi1-dependent Rac activation. Our results define a mechanism whereby propagation of signals, originating from RTKs or Ras and leading to actin reorganization, is controlled by direct physical interaction between PI3K and a Rac-specific GEF complex

A Novel Interhemispheric Interaction: Modulation of Neuronal Cooperativity in the Visual Areas

Background: The cortical representation of the visual field is split along the vertical midline, with the left and the right hemi-fields projecting to separate hemispheres. Connections between the visual areas of the two hemispheres are abundant near the representation of the visual midline. It was suggested that they re-establish the functional continuity of the visual field by controlling the dynamics of the responses in the two hemispheres. Methods/Principal Findings: To understand if and how the interactions between the two hemispheres participate in processing visual stimuli, the synchronization of responses to identical or different moving gratings in the two hemi-fields were studied in anesthetized ferrets. The responses were recorded by multiple electrodes in the primary visual areas and the synchronization of local field potentials across the electrodes were analyzed with a recent method derived from dynamical system theory. Inactivating the visual areas of one hemisphere modulated the synchronization of the stimulus-driven activity in the other hemisphere. The modulation was stimulus-specific and was consistent with the fine morphology of callosal axons in particular with the spatio-temporal pattern of activity that axonal geometry can generate. Conclusions/Significance: These findings describe a new kind of interaction between the cerebral hemispheres and highlight the role of axonal geometry in modulating aspects of cortical dynamics responsible for stimulus detection and/or categorization

Real-time evaluation of longitudinal peak systolic strain (speckle tracking measurement) in left and right ventricles of athletes

<p>Abstract</p> <p>Background</p> <p>Strain, and particularly Longitudinal Peak Systolic Strain (LPSS), plays a role in investigating the segmental and overall contractility of the heart which is a particularly interesting feature in athletes in whom regular training determines several morphological and functional modifications in both the ventricles, that normally work at different loads. Speckle tracking techniques assess the LPSS of LV and RV from B-mode imaging in real time, with uniform accuracy in all segments, and can verify the possible dissimilar segmental contributions of the two chambers to overall myocardial contraction. The aim of the study is to quantify the LPSS in real time in both the ventricles in order to estimate any possible different deformation properties in them during a systolic period.</p> <p>Methods</p> <p>32 subjects (20 athletes and 18 controls) were submitted to a standard echocardiographic examination at rest and after a Hand Grip (HG) stress. From a four-chamber-view image, the LPSS parameter was measured with Speckle Tracking analysis in the basal and medium-apical segments of the two ventricles, at rest and after HG.</p> <p>Results</p> <p>In both athletes and controls, LPSS values were significantly higher in the RV of athletes (RV LPSS ^{medium-apical}-23.87 ± 4.94; ^{basalfreewall}-25.04 ± 4.12 at rest) and controls (RV LPSS^{medium-apical}-25.21 ± 4.97; ^{basalfreewall}-28.69 ± 4.62 at rest) than in the LV of both (athletes LV LPSS ^{medium-apical}-18.14 ± 4.16; ^{basallateralwall}-16.05 ± 12.32; controls ^{medium-apical}-18.81 ± 2.64; ^{basallateralwall}-19.74 ± 3.84) With the HG test a significant enhancement of the LPSS(with P < .05) in the medium-apical segments of LV and RV was evident, but only in athletes; there was no modification of the standard echo-parameters in either group.</p> <p>Conclusion</p> <p>ST analysis is an easy method for investigating the contractility of the RV through deformation parameters, showing greater involvement of the RV than LV at rest. In athletes only, after isometric stress the two ventricles show particular myocardial deformation properties of the regions around the apex where the curvature of the wall is more marked. The clinical application of this new approach in athletes and normal subjects requires further investigation.</p

Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route

Astroglial cells, due to their passive electrical properties, were long considered subservient to neurons and to merely provide the framework and metabolic support of the brain. Although astrocytes do play such structural and housekeeping roles in the brain, these glial cells also contribute to the brain's computational power and behavioural output. These more active functions are endowed by the Ca2+-based excitability displayed by astrocytes. An increase in cytosolic Ca2+ levels in astrocytes can lead to the release of signalling molecules, a process termed gliotransmission, via the process of regulated exocytosis. Dynamic components of astrocytic exocytosis include the vesicular-plasma membrane secretory machinery, as well as the vesicular traffic, which is governed not only by general cytoskeletal elements but also by astrocyte-specific IFs (intermediate filaments). Gliotransmitters released into the ECS (extracellular space) can exert their actions on neighbouring neurons, to modulate synaptic transmission and plasticity, and to affect behaviour by modulating the sleep homoeostat. Besides these novel physiological roles, astrocytic Ca2+ dynamics, Ca2+-dependent gliotransmission and astrocyte–neuron signalling have been also implicated in brain disorders, such as epilepsy. The aim of this review is to highlight the newer findings concerning Ca2+ signalling in astrocytes and exocytotic gliotransmission. For this we report on Ca2+ sources and sinks that are necessary and sufficient for regulating the exocytotic release of gliotransmitters and discuss secretory machinery, secretory vesicles and vesicle mobility regulation. Finally, we consider the exocytotic gliotransmission in the modulation of synaptic transmission and plasticity, as well as the astrocytic contribution to sleep behaviour and epilepsy