RESUMEN
It is known that the primate amygdala forms projections to many areas of the ipsilateral cortex, but the extent to which it forms connections with the contralateral visual cortex remains less understood. Based on retrograde tracer injections in marmoset monkeys, we report that the amygdala forms widespread projections to the ipsilateral extrastriate cortex, including V1 and areas in both the dorsal (MT, V4T, V3a, 19M, and PG/PFG) and the ventral (VLP and TEO) streams. In addition, contralateral projections were found to target each of the extrastriate areas, but not V1. In both hemispheres, the tracer-labeled neurons were exclusively located in the basolateral nuclear complex. The number of labeled neurons in the contralateral amygdala was small relative to the ipsilateral connection (1.2% to 5.8%). The percentage of contralateral connections increased progressively with hierarchical level. An injection in the corpus callosum demonstrated that at least some of the amygdalo-cortical connections cross through this fiber tract, in addition to the previously documented path through the anterior commissure. Our results expand knowledge of the amygdalofugal projections to the extrastriate cortex, while also revealing pathways through which visual stimuli conveying affective content can directly influence early stages of neural processing in the contralateral visual field.
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Amígdala del Cerebelo , Callithrix , Corteza Visual , Animales , Corteza Visual/fisiología , Amígdala del Cerebelo/fisiología , Masculino , Vías Nerviosas/fisiología , Lateralidad Funcional/fisiología , Femenino , Neuronas/fisiología , Cuerpo Calloso/fisiología , Técnicas de Trazados de Vías Neuroanatómicas , Vías Visuales/fisiologíaRESUMEN
The maturation of cerebral cortical networks during early life involves a major reorganization of long-range axonal connections. In a recent study, Bragg-Gonzalo, Aguilera, et al. discovered that in mice, the interhemispheric connections sent by S1L4 callosal projection neurons are pruned via the tight control of their ipsilateral synaptic integration, which relies on the early activity of specific interneurons.
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Corteza Cerebral , Inhibición Neural , Animales , Inhibición Neural/fisiología , Corteza Cerebral/fisiología , Humanos , Neuronas/fisiología , Vías Nerviosas/fisiología , Cuerpo Calloso/fisiología , Interneuronas/fisiología , Red Nerviosa/fisiología , RatonesRESUMEN
During infancy and adolescence, language develops from a predominantly interhemispheric control-through the corpus callosum (CC)-to a predominantly intrahemispheric control, mainly subserved by the left arcuate fasciculus (AF). Using multimodal neuroimaging, we demonstrate that human left-handers (both male and female) with an atypical language lateralization show a rightward participation of language areas from the auditory cortex to the inferior frontal cortex when contrasting speech to tone perception and an enhanced interhemispheric anatomical and functional connectivity. Crucially, musicianship determines two different structural pathways to this outcome. Nonmusicians present a relation between atypical lateralization and intrahemispheric underdevelopment across the anterior AF, hinting at a dysregulation of the ontogenetic shift from an interhemispheric to an intrahemispheric brain. Musicians reveal an alternative pathway related to interhemispheric overdevelopment across the posterior CC and the auditory cortex. We discuss the heterogeneity in reaching atypical language lateralization and the relevance of early musical training in altering the normal development of language cognitive functions.
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Lateralidad Funcional , Música , Humanos , Masculino , Femenino , Música/psicología , Adulto , Lateralidad Funcional/fisiología , Adulto Joven , Lenguaje , Vías Nerviosas/fisiología , Corteza Auditiva/fisiología , Corteza Auditiva/diagnóstico por imagen , Cuerpo Calloso/fisiología , Cuerpo Calloso/diagnóstico por imagen , Imagen por Resonancia Magnética , Adolescente , Mapeo EncefálicoRESUMEN
OBJECTIVES: To investigate potential effects of heading on the neurocognitive performance and the white matter (WM) of the brain in high-level adult male football players. DESIGN: Prospective longitudinal. METHODS: Football players engaging in the highest football leagues in Germany were included. Neurocognitive performance tests and diffusion tensor imaging (DTI) were executed before and after the observation period. Video recordings of each training session and each match play during the observation period were analyzed regarding heading exposure and characteristics. Four DTI measures from tract-based spatial statistics (fractional anisotropy, mean, axial, and radial diffusivity) were investigated. Associations between heading variables and DTI and neurocognitive parameters were tested subsequently. RESULTS: 8052 headers of 22 players (19.9⯱â¯2.7â¯years) were documented in a median of 16.9â¯months. The individual total heading number ranged from 57 to 943 (median: 320.5). Header characteristics differed between training sessions and matches. Neurocognitive performance (nâ¯=â¯22) and DTI measures (nâ¯=â¯14) showed no significant differences from pre- to post-test. After correction for multiple comparisons, no significant correlations with the total heading number were found. However, the change in fractional anisotropy in the splenium of the corpus callosum correlated significantly with the total amount of long-distance headers (Pearson's râ¯=â¯-0.884; pâ¯<â¯0.0001). CONCLUSIONS: Over the median observation period of 16.9â¯months, DTI measures and neurocognitive performance remained unchanged. To elucidate the meaning of the association between individual change in fractional anisotropy and long-distance headers further investigations with larger samples, longer observations, and various cohorts regarding age and level of play are required.
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Imagen de Difusión Tensora , Fútbol , Sustancia Blanca , Humanos , Masculino , Estudios Prospectivos , Adulto Joven , Fútbol/fisiología , Estudios Longitudinales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/anatomía & histología , Sustancia Blanca/fisiología , Adolescente , Cognición/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Encéfalo/anatomía & histología , Alemania , Pruebas Neuropsicológicas , Adulto , Anisotropía , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/anatomía & histología , Cuerpo Calloso/fisiología , Fútbol Americano/fisiologíaRESUMEN
Ideational slippage-characterized by incorrect word usage and strained logic during dialogue-is common in aging and, at greater frequency, is an indicator of pre-clinical cognitive decline. Performance-based assessment of ideational slippage may be useful in the study of cognitive aging and Alzheimer's-disease-related pathology. In this preliminary study, we examine the association between corpus callosum volume and a performance-based assessment of ideational slippage in middle-aged and older adults (age 61-79 years). Ideational slippage was indexed from cognitive special scores using the Rorschach Inkblot Method (RIM), which are validated indices of deviant verbalization and logical inaccuracy (Sum6, WSum6). Among middle-aged and older adults, smaller splenium volume was associated with greater ideational slippage (ηp2 = 0.48), independent of processing speed and fluid intelligence. The observed negative associations are consistent with visuospatial perception and cognitive functions of the splenium. The effect was strongest with the splenium, and volumes of the genu and total white matter had small effects that were not statistically significant. Conclusions: Results are discussed with future application of RIM special scores for the assessment of pre-clinical cognitive decline and, based on observed effect sizes, power analyses are reported to inform future study planning.
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Cuerpo Calloso , Humanos , Persona de Mediana Edad , Anciano , Femenino , Masculino , Cuerpo Calloso/fisiología , Cognición , Envejecimiento/fisiología , Disfunción CognitivaRESUMEN
BACKGROUND: Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS. METHODS: Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS. RESULTS: No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS. CONCLUSION: The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.
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Adaptación Fisiológica , Corteza Motora , Esclerosis Múltiple , Estimulación Magnética Transcraneal , Humanos , Femenino , Masculino , Adulto , Adaptación Fisiológica/fisiología , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Corteza Motora/fisiopatología , Inhibición Neural/fisiología , Marcha/fisiología , Cuerpo Calloso/fisiopatología , Cuerpo Calloso/fisiología , Lateralidad Funcional/fisiología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/etiología , Potenciales Evocados Motores/fisiologíaRESUMEN
The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anteroposterior gradient of vulnerability to aging that may be altered by the effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age = 53.56 ± 18.90; range, 20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion-weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested the effects of age, hypertension, and pulse pressure on these cross-sectional metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age-pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed nonlinear components and occurred along an anteroposterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable and that pulse pressure, a proxy of arterial stiffness, exacerbates this aging pattern in a large lifespan cohort.
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Envejecimiento , Presión Sanguínea , Cuerpo Calloso , Humanos , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/fisiología , Femenino , Persona de Mediana Edad , Anciano , Adulto , Masculino , Envejecimiento/fisiología , Envejecimiento/patología , Anciano de 80 o más Años , Adulto Joven , Presión Sanguínea/fisiología , Imagen de Difusión Tensora , Hipertensión/fisiopatología , Hipertensión/patología , Estudios Transversales , Imagen de Difusión por Resonancia MagnéticaRESUMEN
A recent study by Wang and colleagues disentangled a transcallosal inhibitory circuit in mouse anterior cingulate cortex (ACC), which modulates excitatory ipsilateral tonus and contralateral inhibition by exciting contralateral parvalbumin-positive (PV+) interneurons. The authors conclude that the identified circuit mediates interhemispheric balance for visuospatial attention and provides top-down modulation of visual cortices.
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Cuerpo Calloso , Giro del Cíngulo , Trastornos de la Percepción , Animales , Giro del Cíngulo/fisiología , Ratones , Cuerpo Calloso/fisiología , Trastornos de la Percepción/fisiopatología , Inhibición Neural/fisiologíaRESUMEN
The right-ear advantage (REA) for recalling dichotically presented auditory-verbal stimuli has been traditionally linked to the dominance of the left cerebral hemisphere for speech processing. Early studies on patients with callosotomy additionally found that the removal of the corpus callosum leads to a complete extinction of the left ear, and consequently the today widely used models to explain the REA assume a central role of callosal axons for recalling the left-ear stimulus in dichotic listening. However, later dichotic-listening studies on callosotomy patients challenge this interpretation, as many patients appear to be able to recall left-ear stimuli well above chance level, albeit with reduced accuracy. The aim of the present systematic review was to identify possible experimental and patient variables that explain the inconsistences found regarding the effect of split-brain surgery on dichotic listening. For this purpose, a systematic literature search was conducted (databases: Pubmed, Web of Knowledge, EBSChost, and Ovid) to identify all empirical studies on patients with surgical section of the corpus callosum (complete or partial) that used a verbal dichotic-listening paradigm. This search yielded ks = 32 publications reporting patient data either on case or group level, and the data was analysed by comparing the case-level incidence of left-ear suppression, left-ear extinction, and right-ear enhancement narratively or statistically considering possible moderator variables (i.a., extent of the callosal surgery, stimulus material, response format, selective attention). The main finding was an increased incidence of left-ear suppression (odds ratio = 7.47, CI95%: [1.21; 83.49], exact p = .02) and right-ear enhancement (odds ratio = 21.61, CI95%: [4.40; 154.11], p < .01) when rhyming as compared with non-rhyming stimuli were used. Also, an increase in left-ear reports was apparent when a response by the right hemisphere was allowed (i.e., response with the left hand). While the present review is limited by the overall small number of cases and a lack of an appropriate control sample in most of the original studies, the findings nevertheless suggest an adjustment of the classical dichotic-listening models incorporating right-hemispheric processing abilities as well as the perceptual competition of the left- and right-ear stimuli for attention.
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Percepción Auditiva , Cuerpo Calloso , Pruebas de Audición Dicótica , Humanos , Cuerpo Calloso/cirugía , Cuerpo Calloso/fisiología , Percepción Auditiva/fisiología , Lateralidad Funcional/fisiología , Procedimiento de Escisión Encefálica/métodos , Percepción del Habla/fisiologíaRESUMEN
The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric "heterogeneity" to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.
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Cuerpo Calloso , Neuronas , Animales , Cuerpo Calloso/fisiología , Masculino , Ratones , Neuronas/fisiología , Vías Nerviosas/fisiología , Conectoma , Encéfalo/fisiología , Simulación por Computador , Modelos Neurológicos , Red Nerviosa/fisiología , Calcio/metabolismoRESUMEN
In the mature brain, functionally distinct areas connect to specific targets, mediating network activity required for function. New insights are still occurring regarding how specific connectivity occurs in the developing brain. Decades of work have revealed important insights into the molecular and genetic mechanisms regulating cell type specification in the brain. This work classified long-range projection neurons of the cerebral cortex into three major classes based on their primary target (e.g. subcortical, intracortical, and interhemispheric projections). However, painstaking single-cell mapping reveals that long-range projection neurons of the corpus callosum connect to multiple and overlapping ipsilateral and contralateral targets with often highly branched axons. In addition, their scRNA transcriptomes are highly variable, making it difficult to identify meaningful subclasses. This work has prompted us to reexamine how cortical projection neurons that comprise the corpus callosum are currently classified and how this stunning array of variability might be achieved during development.
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Axones , Neuronas , Neuronas/fisiología , Axones/fisiología , Cuerpo Calloso/fisiología , Corteza Cerebral/fisiología , Vías Nerviosas/fisiologíaRESUMEN
Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.
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Sustancia Blanca , Animales , Humanos , Sustancia Blanca/diagnóstico por imagen , Encéfalo , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/fisiología , Tálamo/diagnóstico por imagen , Macaca mulatta , MamíferosRESUMEN
Prefrontal cortex (PFC) intrahemispheric activity and the interhemispheric connection have a significant impact on neuropsychiatric disorder pathology. This study aimed to generate a functional map of FC intrahemispheric and interhemispheric connections. Functional dissection of mouse PFCs was performed using the voltage-sensitive dye (VSD) imaging method with high speed (1 ms/frame), high resolution (256 × 256 pixels), and a large field of view (â¼10 mm). Acute serial 350 µm slices were prepared from the bregma covering the PFC and numbered 1-5 based on their distance from the bregma (i.e., 1.70, 1.34, 0.98, 0.62, and 0.26 mm) with reference to the Mouse Brain Atlas (Paxinos and Franklin, 2008). The neural response to electrical stimulation was measured at nine sites and then averaged, and a functional map of the propagation patterns was created. Intracortical propagation was observed in slices 3-5, encompassing the anterior cingulate cortex (ACC) and corpus callosum (CC). The activity reached area 33 of the ACC. Direct white matter stimulation activated area 33 in both hemispheres. Similar findings were obtained via DiI staining of the CC. Imaging analysis revealed directional biases in neural signals traveling within the ACC, whereby the signal transmission speed and probability varied based on the signal direction. Specifically, the spread of neural signals from cg2 to cg1 was stronger than that from cingulate cortex area 1(cg1) to cingulate cortex area 2(cg2), which has implications for interhemispheric functional connections. These findings highlight the importance of understanding the PFC functional anatomy in evaluating neuromodulators like serotonin and dopamine, as well as other factors related to neuropsychiatric diseases.
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Cuerpo Calloso , Imagen de Colorante Sensible al Voltaje , Ratones , Animales , Cuerpo Calloso/fisiología , Giro del Cíngulo/fisiología , Corteza Prefrontal/diagnóstico por imagen , Serotonina , Vías Nerviosas/fisiologíaRESUMEN
Barrel cortex integrates contra- and ipsilateral whiskers' inputs. While contralateral inputs depend on the thalamocortical innervation, ipsilateral ones are thought to rely on callosal axons. These are more abundant in the barrel cortex region bordering with S2 and containing the row A-whiskers representation, the row lying nearest to the facial midline. Here, we ask what role this callosal axonal arrangement plays in ipsilateral tactile signaling. We found that novel object exploration with ipsilateral whiskers confines c-Fos expression within the highly callosal subregion. Targeting this area with in vivo patch-clamp recordings revealed neurons with uniquely strong ipsilateral responses dependent on the corpus callosum, as assessed by tetrodotoxin silencing and by optogenetic activation of the contralateral hemisphere. Still, in this area, stimulation of contra- or ipsilateral row A-whiskers evoked an indistinguishable response in some neurons, mostly located in layers 5/6, indicating their involvement in the midline representation of the whiskers' sensory space.
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Corteza Cerebral , Cuerpo Calloso , Cuerpo Calloso/fisiología , Neuronas/fisiología , Axones , Tacto/fisiologíaRESUMEN
Changes in patterns of activity within the medial prefrontal cortex enable rodents, non-human primates and humans to update their behaviour to adapt to changes in the environment-for example, during cognitive tasks1-5. Parvalbumin-expressing inhibitory neurons in the medial prefrontal cortex are important for learning new strategies during a rule-shift task6-8, but the circuit interactions that switch prefrontal network dynamics from maintaining to updating task-related patterns of activity remain unknown. Here we describe a mechanism that links parvalbumin-expressing neurons, a new callosal inhibitory connection, and changes in task representations. Whereas nonspecifically inhibiting all callosal projections does not prevent mice from learning rule shifts or disrupt the evolution of activity patterns, selectively inhibiting only callosal projections of parvalbumin-expressing neurons impairs rule-shift learning, desynchronizes the gamma-frequency activity that is necessary for learning8 and suppresses the reorganization of prefrontal activity patterns that normally accompanies rule-shift learning. This dissociation reveals how callosal parvalbumin-expressing projections switch the operating mode of prefrontal circuits from maintenance to updating by transmitting gamma synchrony and gating the ability of other callosal inputs to maintain previously established neural representations. Thus, callosal projections originating from parvalbumin-expressing neurons represent a key circuit locus for understanding and correcting the deficits in behavioural flexibility and gamma synchrony that have been implicated in schizophrenia and related conditions9,10.
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Aprendizaje , Inhibición Neural , Vías Nerviosas , Neuronas , Parvalbúminas , Corteza Prefrontal , Animales , Ratones , Aprendizaje/fisiología , Neuronas/metabolismo , Parvalbúminas/metabolismo , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Esquizofrenia/fisiopatología , Cuerpo Calloso/citología , Cuerpo Calloso/fisiología , Inhibición Neural/fisiologíaRESUMEN
The concept of a topographical map of the corpus callosum (CC), the main interhemispheric commissure, has emerged from human lesion studies and from anatomical tracing investigations in other mammals. Over the last few years, a rising number of researchers have been reporting functional magnetic resonance imaging (fMRI) activation in also the CC. This short review summarizes the functional and behavioral studies performed in groups of healthy subjects and in patients undergone to partial or total callosal resection, and it is focused on the work conducted by the authors. Functional data have been collected by diffusion tensor imaging and tractography (DTI and DTT) and functional magnetic resonance imaging (fMRI), both techniques allowing to expand and refine our knowledge of the commissure. Neuropsychological test were also administered, and simple behavioral task, as imitation perspective and mental rotation ability, were analyzed. These researches added new insight on the topographic organization of the human CC. By combining DTT and fMRI it was possible to observe that the callosal crossing points of interhemispheric fibers connecting homologous primary sensory cortices, correspond to the CC sites where the fMRI activation elicited by peripheral stimulation was detected. In addition, CC activation during imitation and mental rotation performance was also reported. These studies demonstrated the presence of specific callosal fiber tracts that cross the commissure in the genu, body, and splenium, at sites showing fMRI activation, consistently with cortical activated areas. Altogether, these findings lend further support to the notion that the CC displays a functional topographic organization, also related to specific behavior.
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Cuerpo Calloso , Imagen por Resonancia Magnética , Animales , Humanos , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/cirugía , Cuerpo Calloso/fisiología , Imagen por Resonancia Magnética/métodos , Imagen de Difusión Tensora , MamíferosRESUMEN
The developing neocortex exhibits spontaneous network activity with various synchrony levels, which has been implicated in the formation of cortical circuits. We previously reported that the development of callosal axon projections, one of the major long-range axonal projections in the brain, is activity dependent. However, what sort of activity and when activity is indispensable are not known. Here, using a genetic method to manipulate network activity in a stage-specific manner, we demonstrated that network activity contributes to callosal axon projections in the mouse visual cortex during a 'critical period': restoring neuronal activity during that period resumed the projections, whereas restoration after the period failed. Furthermore, in vivo Ca2+ imaging revealed that the projections could be established even without fully restoring highly synchronous activity. Overall, our findings suggest that spontaneous network activity is selectively required during a critical developmental time window for the formation of long-range axonal projections in the cortex.
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Cuerpo Calloso , Corteza Visual , Animales , Axones/fisiología , Cuerpo Calloso/fisiología , Ratones , Neuronas/fisiología , Corteza Visual/fisiologíaRESUMEN
Traumatic brain injury (TBI) results in deficits that are often followed by recovery. The contralesional cortex can contribute to this process but how distinct contralesional neurons and circuits respond to injury remains to be determined. To unravel adaptations in the contralesional cortex, we used chronic in vivo two-photon imaging. We observed a general decrease in spine density with concomitant changes in spine dynamics over time. With retrograde co-labeling techniques, we showed that callosal neurons are uniquely affected by and responsive to TBI. To elucidate circuit connectivity, we used monosynaptic rabies tracing, clearing techniques and histology. We demonstrate that contralesional callosal neurons adapt their input circuitry by strengthening ipsilateral connections from pre-connected areas. Finally, functional in vivo two-photon imaging demonstrates that the restoration of pre-synaptic circuitry parallels the restoration of callosal activity patterns. Taken together our study thus delineates how callosal neurons structurally and functionally adapt following a contralateral murine TBI.
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Lesiones Traumáticas del Encéfalo , Cuerpo Calloso , Animales , Corteza Cerebral , Cuerpo Calloso/fisiología , Ratones , Neuronas/fisiologíaRESUMEN
The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are two types of cortical projection neurons (CPNs): those that project locally and interhemispherically and those that project to subcerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here, we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during mouse brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate (CP) during the formation of the superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditional loss-of-function and gain-of-function analysis we show that Mllt11 is required for neuritogenesis and proper migration of upper layer CPNs. Loss of Mllt11 in the superficial cortex of male and female neonates leads to a severe reduction in fibers crossing the corpus callosum (CC), a progressive loss in the maintenance of upper layer projection neuron gene expression, and reduced complexity of dendritic arborization. Proteomic analysis revealed that Mllt11 associates with stabilized microtubules, and Mllt11 loss affected microtubule staining in callosal axons. Taken together, our findings support a role for Mllt11 in promoting the formation of mature upper-layer neuron morphologies and connectivity in the cerebral cortex.SIGNIFICANCE STATEMENT The regulation of cortical projection neuron (CPN) morphologies is an area of active investigation since the time of Cajal. Yet the molecular mechanisms of how the complex dendritic and axonal morphologies of projection neurons are formed remains incompletely understood. Although conditional mutagenesis analysis in the mouse, coupled with overexpression assays in the developing fetal brain, we show that a novel protein called Mllt11 is sufficient and necessary to regulate the dendritic and axonal characteristics of callosal projection neurons in the developing mammalian neocortex. Furthermore, we show that Mllt11 interacts with microtubules, likely accounting for its role in neuritogenesis.
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Corteza Cerebral , Neocórtex , Proyección Neuronal , Proteínas Proto-Oncogénicas , Animales , Axones/fisiología , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Cuerpo Calloso/fisiología , Femenino , Masculino , Ratones , Neocórtex/metabolismo , Vías Nerviosas/fisiología , Neuronas/fisiología , Proteómica , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/fisiologíaRESUMEN
The visual system forms the basis of visual word decoding processes. Reading is a left-lateralized function. The interaction between the two hemispheres via the corpus callosum is required for successful reading. It is known that callosal function and morphology are affected in reading disorders. This study investigated the differences in callosal transfer speed of verbal and nonverbal stimuli in healthy university students. We hypothesized that if the callosal transfer has a role in slow reading, transfer speed would differ between slow and fast readers. Moreover, if the difference was affected by the type of stimulus, this will provide information about the level of neural processing at which the difference is based/aroused. Fifty-one participants were grouped as slow (n = 15, 8 female) and fast (n = 36, 22 female) readers. Three types of stimuli (word, legal pseudoword, and non-verbal grating) were presented from the right or left visual field. Latencies of the evoked potentials (N1) were used to measure interhemispheric transfer time. We found that slow readers have a slower right-to-left transfer speed at the parietal site, which is related to the visual word decoding process. The finding was similar to previous studies examining individuals with dyslexia. This difference was not seen with grating stimuli; we suggest that the difference originates at the orthographic visual lexical level rather than at earlier basic visual processing. We did not observe any effect of lexical and sublexical routes on the callosal transfer time because of evaluated time windows.