Thalamocortical axons regulate neurogenesis and laminar fates in the early sensory cortex

Dissociation of Corticothalamic and Thalamocortical Axon Targeting by an EphA7-Mediated Mechanism

Tangential Neuronal Migration Controls Axon Guidance: A Role for Neuregulin-1 in Thalamocortical Axon Navigation

Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity.

To simulate the concept acquisition and binding of different senses in the brain, a biologically inspired neural network model named perception coordination network (PCN) is proposed. It is a hierarchical structure, which is functionally divided into the primary sensory area (PSA), the primary sensory association area (SAA), and the higher order association area (HAA). The PSA contains feature neurons which respond to many elementary features, e.g., colors, shapes, syllables, and basic flavors. The SAA contains primary concept neurons which combine the elementary features in the PSA to represent unimodal concept of objects, e.g., the image of an apple, the Chinese word "[píng guǒ]" which names the apple, and the taste of the apple. The HAA contains associated neurons which connect the primary concept neurons of several PSA, e.g., connects the image, the taste, and the name of an apple. It means that the associated neurons have a multimodal response mode. Therefore, this area executes multisensory integration. PCN is an online incremental learning system, it is able to continuously acquire and bind multimodality concepts in an online way. The experimental results suggest that PCN is able to handle the multimodal concept acquisition and binding effectively.

To learn about maturational patterns of nonpyramidal neurons in the cerebral cortex, calbindin-D28k immunoreactivity was studied in the kitten cortex. Immunoreactive neurons first appear in the cortical and subcortical areas related to the limbic system, including the cingulate and retrosplenial cortices, and in the secondary motor areas. These are followed by the primary motor and sensory association areas and, finally, by the primary sensory areas. In all cortical areas, calbindin-D28k immunoreactivity first develops in layer V pyramidal neurons and later in nonpyramidal neurons, except in the primary sensory areas, where immunoreactive pyramidal neurons are not found at any age. Transient calbindin-D28k immunoreactivity occurs in pyramidal neurons that are mainly localized in the cingulate and retrosplenial cortices and in the secondary motor area, as well as in nonpyramidal neurons localized in the subplate and layer I, and in a subset of large multipolar and bitufted neurons in layer VI. Nonpyramidal neurons localized in layers II to IV, and some neurons in layer VI, develop permanent calbindin-D28k immunoreactivity. Calbindin-D28k immunoreactivity labels subsets of GABAergic interneurons that form vertical axonal tufts, so that temporal and regional patterns of calbindin-D28k immunoreactivity during development may be implicated in the maturation of columnar (vertical) inhibition in the cerebral cortex. In addition to neurons, corticofugal and afferent fibres of subcortical origin exhibit calbindin-D28k immunoreactivity. Transient calbindin-D28k immunoreactivity occurs in corticofugal fibres arising from the cingulate and prefrontal cortices, which are probably corticostriatal projection fibres. In contrast, permanent immunoreactivity occurs in what are probably thalamocortical fibres ending in layer IV, and in punctate terminals located in the upper third of layer I.

The cerebral cortex is an anatomically divided and functionally specialized structure. It includes distinct areas, which work on different states over time. The structural features of spiking activity in sensory cortices have been characterized during spontaneous and evoked activity. However, the coordination among cortical and sub-cortical neurons during spontaneous activity across different states remains poorly characterized. We addressed this issue by studying the temporal coupling of spiking variability recorded from primary sensory cortices and hippocampus of anesthetized or freely behaving rats. During spontaneous activity, spiking variability was highly correlated across primary cortical sensory areas at both small and large spatial scales, whereas the cortico-hippocampal correlation was modest. This general pattern of spiking variability was observed under urethane anesthesia, as well as during waking, slow-wave sleep and rapid-eye-movement sleep, and was unchanged by novel stimulation. These results support the notion that primary sensory areas are strongly coupled during spontaneous activity.

Continuously prioritizing behaviourally relevant information from the environment for improved stimulus processing is a crucial function of attention. In the current MEG study, we investigated how ongoing oscillatory activity of both sensory and non-sensory brain regions are differentially impacted by attentional focus. Low-frequency phase alignment of neural activity in primary sensory areas, with respect to attended/ignored features has been suggested to support top-down prioritization. However, phase adjustment in frontoparietal regions has not been widely studied, despite general implication of these in top-down selection of information. To investigate this, we let participants perform an established intermodal selective attention task, where low-frequency auditory (1.6 Hz) and visual (1.8 Hz) stimuli were presented simultaneously. We instructed them to either attend to the auditory or to the visual stimuli and to detect targets while ignoring the other stimulus stream. As expected, the strongest phase adjustment was observed in primary sensory regions for auditory and for visual stimulation, independent of attentional focus. We found greater differences in phase locking between attended and ignored stimulation for the visual modality. Interestingly, auditory temporal regions show small but significant attention-dependent neural entrainment even for visual stimulation. Extending findings from invasive recordings in non-human primates, we demonstrate an effect of attentional focus on the phase of the entrained oscillations in auditory and visual cortex which may be driven by phase locked increases of induced power. While sensory areas adjusted the phase of the respective stimulation frequencies, attentional focus adjusted the peak frequencies in nonsensory areas. Spatially these areas show a striking overlap with core regions of the dorsal attention network and the frontoparietal network. This suggests that these areas prioritize the attended modality by optimally exploiting the temporal structure of stimulation. Overall, our study complements and extends previous work by showing a differential effect of attentional focus on entrained oscillations (or phase adjustment) in primary sensory areas and frontoparietal areas.

In complex natural environments, auditory and visual information often have to be processed simultaneously. Previous functional magnetic resonance imaging (fMRI) studies focused on the spatial localization of brain areas involved in audiovisual (AV) information processing, but the temporal characteristics of AV information flow in these regions remained unclear. In this study, we used fMRI and a novel information-theoretic approach to study the flow of AV sensory information. Subjects passively perceived sounds and images of objects presented either alone or simultaneously. Applying the measure of mutual information, we computed for each voxel the latency in which the blood oxygenation level-dependent signal had the highest information content about the preceding stimulus. The results indicate that, after AV stimulation, the earliest informative activity occurs in right Heschl's gyrus, left primary visual cortex, and the posterior portion of the superior temporal gyrus, which is known as a region involved in object-related AV integration. Informative activity in the anterior portion of superior temporal gyrus, middle temporal gyrus, right occipital cortex, and inferior frontal cortex was found at a later latency. Moreover, AV presentation resulted in shorter latencies in multiple cortical areas compared with isolated auditory or visual presentation. The results provide evidence for bottom-up processing from primary sensory areas into higher association areas during AV integration in humans and suggest that AV presentation shortens processing time in early sensory cortices.

In humans, neurofeedback (NFB) training has been used extensively and successfully to manipulate brain activity. Feedback signals were derived from EEG, fMRI, MEG, and intracranial recordings and modifications were obtained of the BOLD signal, of the power of oscillatory activity in distinct frequency bands and of single unit activity. The purpose of the present study was to examine whether neuronal activity could also be controlled by NFB in early sensory cortices whose activity is thought to be influenced mainly by sensory input rather than volitional control. We trained 2 macaque monkeys to enhance narrow band gamma oscillations in the primary visual cortex by providing them with an acoustic signal that reflected the power of gamma oscillations in a preselected band and rewarding increases of the feedback signal. Oscillations were assessed from local field potentials recorded with chronically implanted microelectrodes. Both monkeys succeeded to raise gamma activity in the absence of visual stimulation in the selected frequency band and at the site from which the NFB signal was derived. This suggests that top-down signals are not confined to just modulate stimulus induced responses but can actually drive or facilitate the gamma generating microcircuits even in a primary sensory area.

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Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.

The development of serotonergic innervation to rat cerebral cortex was characterized by immunohistochemical localization of serotonin combined with autoradiographic imaging of serotonin-uptake sites. In neonatal rat, a transient, dense, serotonergic innervation appears in all primary sensory areas of cortex. In somatosensory cortex, dense patches of serotonergic innervation are aligned with specialized cellular aggregates called barrels. The dense patches are not apparent after 3 weeks of age, and the serotonergic innervation becomes more uniform in adult neocortex. This precocious neonatal serotonergic innervation may play a transient physiologic role in sensory areas of cortex or may exert a trophic influence on the development of cortical circuitry and thalamocortical connections.

Direct evidence of the anatomical localization of brain function is provided by functional neurological changes during awake surgery combined with data from preoperative functional magnetic resonance imaging and diffusion tensor imaging studies. The goal of the present study was to analyze the etiology and mechanism of motor hemineglect using these techniques. Of 29 patients with brain tumors within and near the primary motor area (M1) in whom awake surgery was employed from April 2004 through March 2007, 2 patients evinced motor hemineglect of the left hand during awake surgery. The brain tumors in these 2 cases alone were located just beside the hand area of M1 and the primary sensory area (S1) in the right hemisphere. In case 1, the U fibers that connected the areas activated by hand clenching in M1 with S1 were compressed by the brain tumor. These results suggest that the combination of damage to the right hemispheric hand area in M1 and S1 plays a critical role in the development of motor hemineglect.

In mammals, the neocortical layout consists of few modality-specific primary sensory areas and a multitude of higher order ones. Abnormal layout of cortical areas may disrupt sensory function and behavior. Developmental genetic mechanisms specify primary areas, but mechanisms influencing higher order area properties are unknown. By exploiting gain-of and loss-of function mouse models of the transcription factor Emx2, we have generated bi-directional changes in primary visual cortex size in vivo and have used it as a model to show a novel and prominent function for genetic mechanisms regulating primary visual area size and also proportionally dictating the sizes of surrounding higher order visual areas. This finding redefines the role for intrinsic genetic mechanisms to concomitantly specify and scale primary and related higher order sensory areas in a linear fashion.

Associational connections of pyramidal cells in rat posterior piriform cortex were studied by direct visualization of axons stained by intracellular injection in vivo. The results revealed that individual cells have widespread axonal arbors that extend over nearly the full length of the cerebral hemisphere. Within piriform cortex these arbors are highly distributed with no regularly arranged patchy concentrations like those associated with the columnar organization in other primary sensory areas (i.e., where periodically arranged sets of cells have common response properties, inputs, and outputs). A lack of columnar organization was also indicated by a marked disparity in the intrinsic projection patterns of neighboring injected cells. Analysis of axonal branching patterns, bouton distributions, and dendritic arbors suggested that each pyramidal cell makes a small number of synaptic contacts on a large number (>1000) of other cells in piriform cortex at disparate locations. Axons from individual pyramidal cells also arborize extensively within many neighboring cortical areas, most of which send strong projections back to piriform cortex. These include areas involved in high-order functions in prefrontal, amygdaloid, entorhinal, and perirhinal cortex, to which there are few projections from other primary sensory areas. Our results suggest that piriform cortex performs correlative functions analogous to those in association areas of neocortex rather than those typical of primary sensory areas with which it has been traditionally classed. Findings from other studies suggest that the olfactory bulb subserves functions performed by primary areas in other sensory systems.