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1.
Hum Brain Mapp ; 42(14): 4580-4596, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34219304

RESUMEN

The importance of (inherited) genetic impact in reading development is well established. De novo mutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor for de novo mutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offspring's reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was significantly associated with worse reading, explaining an additional 9.5% of the variance after controlling for a number of confounds-including familial factors and cognitive-linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE-related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offspring's diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research.


Asunto(s)
Dislexia , Red Nerviosa , Edad Paterna , Lectura , Tálamo , Niño , Preescolar , Estudios Transversales , Dislexia/diagnóstico por imagen , Dislexia/etiología , Dislexia/patología , Dislexia/fisiopatología , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/anatomía & histología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/crecimiento & desarrollo , Pulvinar/anatomía & histología , Pulvinar/diagnóstico por imagen , Pulvinar/crecimiento & desarrollo , Tálamo/anatomía & histología , Tálamo/diagnóstico por imagen , Tálamo/crecimiento & desarrollo
2.
Nutrients ; 12(9)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899673

RESUMEN

Recent studies have shown that maternal supplementation with folate and long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy may affect children's brain development. We aimed at examining the potential long-term effect of maternal supplementation with fish oil (FO) and/or 5-methyl-tetrahydrofolate (5-MTHF) on the brain functionality of offspring at the age of 9.5-10 years. The current study was conducted as a follow-up of the Spanish participants belonging to the Nutraceuticals for a Healthier Life (NUHEAL) project; 57 children were divided into groups according to mother's supplementation and assessed through functional magnetic resonance imaging (fMRI) scanning and neurodevelopment testing. Independent component analysis and double regression methods were implemented to investigate plausible associations. Children born to mothers supplemented with FO (FO and FO + 5-MTHF groups, n = 33) showed weaker functional connectivity in the default mode (DM) (angular gyrus), the sensorimotor (SM) (motor and somatosensory cortices) and the fronto-parietal (FP) (angular gyrus) networks compared to the No-FO group (placebo and 5-MTHF groups, n = 24) (PFWE < 0.05). Furthermore, no differences were found regarding the neuropsychological tests, except for a trend of better results in an object recall (memory) test. Considering the No-FO group, the aforementioned networks were associated negatively with attention and speed-processing functions. Mother's FO supplementation during pregnancy seems to be able to shape resting-state network functioning in their children at school age and appears to produce long-term effects on children´s cognitive processing.


Asunto(s)
Encéfalo/crecimiento & desarrollo , Desarrollo Infantil/efectos de los fármacos , Suplementos Dietéticos , Aceites de Pescado/administración & dosificación , Fenómenos Fisiologicos Nutricionales Maternos/efectos de los fármacos , Tetrahidrofolatos/administración & dosificación , Adulto , Encéfalo/diagnóstico por imagen , Niño , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Exposición Materna , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/crecimiento & desarrollo , Embarazo , Análisis de Componente Principal , Análisis de Regresión , Descanso/fisiología
3.
Prog Neurobiol ; 194: 101883, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32659318

RESUMEN

The most prominent transient compartment of the primate fetal cortex is the deep, cell-sparse, synapse-containing subplate compartment (SPC). The developmental role of the SPC and its extraordinary size in humans remain enigmatic. This paper evaluates evidence on the development and connectivity of the SPC and discusses its role in the pathogenesis of neurodevelopmental disorders. A synthesis of data shows that the subplate becomes a prominent compartment by its expansion from the deep cortical plate (CP), appearing well-delineated on MR scans and forming a tangential nexus across the hemisphere, consisting of an extracellular matrix, randomly distributed postmigratory neurons, multiple branches of thalamic and long corticocortical axons. The SPC generates early spontaneous non-synaptic and synaptic activity and mediates cortical response upon thalamic stimulation. The subplate nexus provides large-scale interareal connectivity possibly underlying fMR resting-state activity, before corticocortical pathways are established. In late fetal phase, when synapses appear within the CP, transient the SPC coexists with permanent circuitry. The histogenetic role of the SPC is to provide interactive milieu and capacity for guidance, sorting, "waiting" and target selection of thalamocortical and corticocortical pathways. The new evolutionary role of the SPC and its remnant white matter neurons is linked to the increasing number of associative pathways in the human neocortex. These roles attributed to the SPC are regulated using a spatiotemporal gene expression during critical periods, when pathogenic factors may disturb vulnerable circuitry of the SPC, causing neurodevelopmental cognitive circuitry disorders.


Asunto(s)
Desarrollo Fetal/fisiología , Neocórtex/crecimiento & desarrollo , Red Nerviosa/crecimiento & desarrollo , Vías Nerviosas/crecimiento & desarrollo , Trastornos del Neurodesarrollo/fisiopatología , Neuronas/fisiología , Tálamo/crecimiento & desarrollo , Animales , Humanos , Neocórtex/embriología , Red Nerviosa/embriología , Vías Nerviosas/embriología , Trastornos del Neurodesarrollo/etiología , Tálamo/embriología
4.
J Neurophysiol ; 123(5): 1583-1599, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32049596

RESUMEN

Nervous system maturation occurs on multiple levels-synaptic, circuit, and network-at divergent timescales. For example, many synaptic properties mature gradually, whereas emergent network dynamics can change abruptly. Here we combine experimental and theoretical approaches to investigate a sudden transition in spontaneous and sensory evoked thalamocortical activity necessary for the development of vision. Inspired by in vivo measurements of timescales and amplitudes of synaptic currents, we extend the Wilson and Cowan model to take into account the relative onset timing and amplitudes of inhibitory and excitatory neural population responses. We study this system as these parameters are varied within amplitudes and timescales consistent with developmental observations to identify the bifurcations of the dynamics that might explain the network behaviors in vivo. Our findings indicate that the inhibitory timing is a critical determinant of thalamocortical activity maturation; a gradual decay of the ratio of inhibitory to excitatory onset time drives the system through a bifurcation that leads to a sudden switch of the network spontaneous activity from high-amplitude oscillations to a nonoscillatory active state. This switch also drives a change from a threshold bursting to linear response to transient stimuli, also consistent with in vivo observation. Thus we show that inhibitory timing is likely critical to the development of network dynamics and may underlie rapid changes in activity without similarly rapid changes in the underlying synaptic and cellular parameters.NEW & NOTEWORTHY Relying on a generalization of the Wilson-Cowan model, which allows a solid analytic foundation for the understanding of the link between maturation of inhibition and network dynamics, we propose a potential explanation for the role of developing excitatory/inhibitory synaptic delays in mediating a sudden switch in thalamocortical visual activity preceding vision onset.


Asunto(s)
Corteza Cerebral/fisiología , Fenómenos Electrofisiológicos/fisiología , Modelos Teóricos , Red Nerviosa/fisiología , Tálamo/fisiología , Animales , Corteza Cerebral/crecimiento & desarrollo , Humanos , Red Nerviosa/crecimiento & desarrollo , Tálamo/crecimiento & desarrollo
5.
Exp Aging Res ; 45(1): 41-56, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30633644

RESUMEN

Background/Study context: Posture and gait are complex sensorimotor functions affected by age. These difficulties are particularly apparent when performing cognitively demanding tasks. Characterizing the functional organization of brain networks involved in these associations remains a challenge because of the incompatibility of brain imagery techniques with gross body movements. The present study aimed at testing whether resting-state functional connectivity of sensorimotor networks is associated with posture and gait performance recorded offline, in young and older adults. METHODS: Young (n = 12, mean = 24.1 y/o) and older (n = 14, mean = 65.6 y/o) healthy adults were tested for stability of their posture and gait. Four hours later, anatomical and functional brain imaging data were collected with Magnetic Resonance Imaging (MRI). Bilateral precentral and postcentral gyri were used as seeds in a graph theory analysis focused on global and local efficiency. The possible association between these data and posture and gait performance was examined. RESULTS: Both samples presented similar sensorimotor graphs, but with different global and local efficiencies (small world properties). The association between the networks' graph measures and posture and gait performance also differed across groups: local efficiency was correlated with gait stability in challenging conditions in older adults, but not in young adults. CONCLUSION: This exploratory study suggests that combining analyses of functional networks and offline body movement may provide important information about motor function. In older adults, the association between graph properties of the sensorimotor network and gait performance in challenging conditions may be indicative of compensatory processes. Prospective studies involving more subjects with a larger age range are warranted.


Asunto(s)
Envejecimiento/fisiología , Envejecimiento/psicología , Marcha/fisiología , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/fisiología , Postura/fisiología , Anciano , Mapeo Encefálico , Cognición/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Estudios Prospectivos , Prueba de Secuencia Alfanumérica , Adulto Joven
6.
J Neurochem ; 147(5): 626-646, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30326149

RESUMEN

Visual information is detected by the retina and transmitted into the brain by retinal ganglion cells. In rodents, the visual thalamus is a major recipient of retinal ganglion cells axons and is divided into three functionally distinct nuclei: the dorsal lateral geniculate nucleus (dLGN), ventral LGN (vLGN), and intergeniculate leaflet. Despite being densely innervated by retinal input, each nucleus in rodent visual thalamus possesses diverse molecular profiles which underpin their unique circuitry and cytoarchitecture. Here, we combined large-scale unbiased proteomic and transcriptomic analyses to elucidate the molecular expression profiles of the developing mouse dLGN and vLGN. We identified several extracellular matrix proteins as differentially expressed in these regions, particularly constituent molecules of perineuronal nets (PNNs). Remarkably, we discovered at least two types of molecularly distinct Aggrecan-rich PNN populations in vLGN, exhibiting non-overlapping spatial, temporal, and cell-type specific expression patterns. The mechanisms responsible for the formation of these two populations of PNNs also differ as the formation of Cat315+ PNNs (but not WFA+ PNNs) required input from the retina. This study is first to suggest that cell type- and molecularly specific supramolecular assemblies of extracellular matrix may play important roles in the circuitry associated with the subcortical visual system and in the processing of visual information. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14203.


Asunto(s)
Red Nerviosa/metabolismo , Tálamo/metabolismo , Visión Ocular/fisiología , Animales , Matriz Extracelular/metabolismo , Matriz Extracelular/fisiología , Proteínas de la Matriz Extracelular/metabolismo , Cuerpos Geniculados/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Red Nerviosa/crecimiento & desarrollo , Proteómica , Reacción en Cadena en Tiempo Real de la Polimerasa , Retina/fisiología , Células Ganglionares de la Retina/fisiología , Tálamo/crecimiento & desarrollo , Percepción Visual/fisiología
7.
Curr Opin Neurobiol ; 52: 165-171, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30032064

RESUMEN

From birth, mammals have to find food and maximize caloric intake to ensure growth and survival. Suckling must be initiated quickly after birth and then maintained and controlled until weaning. It is a complex process involving interactions between sensory and motor neuronal pathways. Meanwhile, the control of food intake and energy homeostasis is progressively established via the development of hypothalamic circuits. The development of these circuits is influenced by hormonal and nutritional signals and can be disturbed in a variety of developmental disorders leading to long-term metabolic, behavioral and cognitive dysfunctions. This review summarizes our current knowledge of the neuronal circuits involved in early postnatal feeding processes.


Asunto(s)
Conducta Alimentaria/fisiología , Homeostasis/fisiología , Hipotálamo/fisiología , Red Nerviosa/fisiología , Percepción Olfatoria/fisiología , Conducta en la Lactancia/fisiología , Percepción del Tacto/fisiología , Animales , Humanos , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/metabolismo
8.
Curr Opin Neurobiol ; 52: 72-79, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29715588

RESUMEN

Thalamocortical activity patterns, both spontaneous and evoked, undergo a dramatic shift in preparation for the onset of rich sensory experience (e.g. birth in humans; eye-opening in rodents). This change is the result of a switch from thalamocortical circuits tuned for transmission of spontaneous bursting in sense organs, to circuits capable of high resolution, active sensory processing. Early 'pre-sensory' tuning uses amplification generated by corticothalamic excitatory feedback and early-born subplate neurons to ensure transmission of bursts, at the expense of stimulus discrimination. The switch to sensory circuits is due, at least in part, to the coordinated remodeling of inhibitory circuits in thalamus and cortex. Appreciation of the distinct rules that govern early circuit function can, and should, inform translational studies of genetic and acquired developmental dysfunction.


Asunto(s)
Corteza Cerebral/fisiología , Fenómenos Electrofisiológicos/fisiología , Red Nerviosa/fisiología , Sensación/fisiología , Tálamo/fisiología , Animales , Corteza Cerebral/crecimiento & desarrollo , Humanos , Red Nerviosa/crecimiento & desarrollo , Tálamo/crecimiento & desarrollo
9.
Science ; 359(6381): 1269-1273, 2018 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-29420261

RESUMEN

Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.


Asunto(s)
Astrocitos/metabolismo , Sistema Nervioso Central/crecimiento & desarrollo , Interleucina-33/metabolismo , Microglía/fisiología , Red Nerviosa/crecimiento & desarrollo , Neurogénesis , Sinapsis/fisiología , Animales , Sistema Nervioso Central/metabolismo , Homeostasis , Interleucina-33/genética , Ratones , Ratones Noqueados , Corteza Sensoriomotora/crecimiento & desarrollo , Corteza Sensoriomotora/fisiología , Tálamo/anomalías
10.
Physiol Res ; 66(5): 867-880, 2017 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-29020454

RESUMEN

Brain-specific link protein Bral2 represents a substantial component of perineuronal nets (PNNs) enwrapping neurons in the central nervous system. To elucidate the role of Bral2 in auditory signal processing, the hearing function in knockout Bral2(-/-) (KO) mice was investigated using behavioral and electrophysiological methods and compared with wild type Bral2(+/+) (WT) mice. The amplitudes of the acoustic startle reflex (ASR) and the efficiency of the prepulse inhibition of ASR (PPI of ASR), produced by prepulse noise stimulus or gap in continuous noise, was similar in 2-week-old WT and KO mice. Over the 2-month postnatal period the increase of ASR amplitudes was significantly more evident in WT mice than in KO mice. The efficiency of the PPI of ASR significantly increased in the 2-month postnatal period in WT mice, whereas in KO mice the PPI efficiency did not change. Hearing thresholds in 2-month-old WT mice, based on the auditory brainstem response (ABR) recordings, were significantly lower at high frequencies than in KO mice. However, amplitudes and peak latencies of individual waves of click-evoked ABR did not differ significantly between WT and KO mice. Temporal resolution and neural adaptation were significantly better in 2-month-old WT mice than in age-matched KO mice. These results support a hypothesis that the absence of perineuronal net formation at the end of the developmental period in the KO mice results in higher hearing threshold at high frequencies and weaker temporal resolution ability in adult KO animals compared to WT mice.


Asunto(s)
Estimulación Acústica/métodos , Adaptación Fisiológica/fisiología , Proteínas de la Matriz Extracelular/deficiencia , Red Nerviosa/metabolismo , Proteínas del Tejido Nervioso/deficiencia , Inhibición Prepulso/fisiología , Reflejo de Sobresalto/fisiología , Factores de Edad , Animales , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Red Nerviosa/crecimiento & desarrollo , Nervios Periféricos/crecimiento & desarrollo , Nervios Periféricos/metabolismo , Factores de Tiempo
11.
Dev Cogn Neurosci ; 19: 211-22, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27104668

RESUMEN

Feedback learning is a crucial skill for cognitive flexibility that continues to develop into adolescence, and is linked to neural activity within a frontoparietal network. Although it is well conceptualized that activity in the frontoparietal network changes during development, there is surprisingly little consensus about the direction of change. Using a longitudinal design (N=208, 8-27 years, two measurements in two years), we investigated developmental trajectories in frontoparietal activity during feedback learning. Our first aim was to test for linear and nonlinear developmental trajectories in dorsolateral prefrontal cortex (DLPFC), superior parietal cortex (SPC), supplementary motor area (SMA) and anterior cingulate cortex (ACC). Second, we tested which factors (task performance, working memory, cortical thickness) explained additional variance in time-related changes in activity besides age. Developmental patterns for activity in DLPFC and SPC were best characterized by a quadratic age function leveling off/peaking in late adolescence. There was a linear increase in SMA and a linear decrease with age in ACC activity. In addition to age, task performance explained variance in DLPFC and SPC activity, whereas cortical thickness explained variance in SMA activity. Together, these findings provide a novel perspective of linear and nonlinear developmental changes in the frontoparietal network during feedback learning.


Asunto(s)
Biorretroalimentación Psicológica/fisiología , Lóbulo Frontal/fisiología , Memoria a Corto Plazo/fisiología , Lóbulo Parietal/fisiología , Desempeño Psicomotor/fisiología , Adolescente , Adulto , Factores de Edad , Mapeo Encefálico/tendencias , Niño , Femenino , Lóbulo Frontal/crecimiento & desarrollo , Humanos , Aprendizaje/fisiología , Estudios Longitudinales , Imagen por Resonancia Magnética/tendencias , Masculino , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/fisiología , Tamaño de los Órganos , Lóbulo Parietal/crecimiento & desarrollo , Estimulación Luminosa/métodos , Adulto Joven
12.
J Physiol ; 594(10): 2579-92, 2016 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-26864476

RESUMEN

KEY POINTS: The thalamus is a structure critical for information processing and transfer to the cortex. Thalamic reticular neurons are inhibitory cells interconnected by electrical synapses, most of which require the gap junction protein connexin36 (Cx36). We investigated whether electrical synapses play a role in the maturation of thalamic networks by studying neurons in mice with and without Cx36. When Cx36 was deleted, inhibitory synapses were more numerous, although both divergent inhibitory connectivity and dendritic complexity were reduced. Surprisingly, we observed non-Cx36-dependent electrical synapses with unusual biophysical properties interconnecting some reticular neurons in mice lacking Cx36. The results of the present study suggest an important role for Cx36-dependent electrical synapses in the development of thalamic circuits. ABSTRACT: Neurons within the mature thalamic reticular nucleus (TRN) powerfully inhibit ventrobasal (VB) thalamic relay neurons via GABAergic synapses. TRN neurons are also coupled to one another by electrical synapses that depend strongly on the gap junction protein connexin36 (Cx36). Electrical synapses in the TRN precede the postnatal development of TRN-to-VB inhibition. We investigated how the deletion of Cx36 affects the maturation of TRN and VB neurons, electrical coupling and GABAergic synapses by studying wild-type (WT) and Cx36 knockout (KO) mice. The incidence and strength of electrical coupling in TRN was sharply reduced, but not abolished, in KO mice. Surprisingly, electrical synapses between Cx36-KO neurons had faster voltage-dependent decay kinetics and conductance asymmetry (rectification) than did electrical synapses between WT neurons. The properties of TRN-mediated inhibition in VB also depended on the Cx36 genotype. Deletion of Cx36 increased the frequency and shifted the amplitude distributions of miniature IPSCs, whereas the paired-pulse ratio of evoked IPSCs was unaffected, suggesting that the absence of Cx36 led to an increase in GABAergic synaptic contacts. VB neurons from Cx36-KO mice also tended to have simpler dendritic trees and fewer divergent inputs from the TRN compared to WT cells. The findings obtained in the present study suggest that proper development of thalamic inhibitory circuitry, neuronal morphology, TRN cell function and electrical coupling requires Cx36. In the absence of Cx36, some TRN neurons express asymmetric electrical coupling mediated by other unidentified connexin subtypes.


Asunto(s)
Conexinas/deficiencia , Sinapsis Eléctricas/fisiología , Potenciales Postsinápticos Inhibidores/fisiología , Red Nerviosa/crecimiento & desarrollo , Inhibición Neural/fisiología , Tálamo/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Femenino , Masculino , Ratones , Ratones Noqueados , Red Nerviosa/metabolismo , Técnicas de Cultivo de Órganos , Tálamo/metabolismo , Proteína delta-6 de Union Comunicante
13.
J Neurosci ; 34(27): 9067-75, 2014 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-24990927

RESUMEN

Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy.


Asunto(s)
Mapeo Encefálico , Corteza Cerebral/crecimiento & desarrollo , Desarrollo Infantil , Cognición/fisiología , Red Nerviosa/crecimiento & desarrollo , Tálamo/crecimiento & desarrollo , Corteza Cerebral/fisiología , Femenino , Estudios de Seguimiento , Juegos Experimentales , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Red Nerviosa/fisiología , Vías Nerviosas/crecimiento & desarrollo , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , Conducta Espacial/fisiología , Tálamo/fisiología
14.
Dev Neurosci ; 36(3-4): 175-95, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24819672

RESUMEN

Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of changes in brain remodeling that occur during adolescence. This study sought to investigate developmental changes in EROs using a similar auditory event-related potential (ERP) paradigm in both rats and humans. Energy and phase variability of EROs collected from 38 young adult men (aged 18-25 years), 33 periadolescent boys (aged 10-14 years), 15 male periadolescent rats [at postnatal day (PD) 36] and 19 male adult rats (at PD103) were investigated. Three channels of ERP data (frontal cortex, central cortex and parietal cortex) were collected from the humans using an 'oddball plus noise' paradigm that was presented under passive (no behavioral response required) conditions in the periadolescents and under active conditions (where each subject was instructed to depress a counter each time he detected an infrequent target tone) in adults and adolescents. ERPs were recorded in rats using only the passive paradigm. In order to compare the tasks used in rats to those used in humans, we first studied whether three ERO measures [energy, phase locking index (PLI) within an electrode site and phase difference locking index (PDLI) between different electrode sites] differentiated the 'active' from 'passive' ERP tasks. Secondly, we explored our main question of whether the three ERO measures differentiated adults from periadolescents in a similar manner in both humans and rats. No significant changes were found in measures of ERO energy between the active and passive tasks in the periadolescent human participants. There was a smaller but significant increase in PLI but not PDLI as a function of active task requirements. Developmental differences were found in energy, PLI and PDLI values between the periadolescents and adults in both the rats and the human participants. Neuronal synchrony as indexed by PLI and PDLI was significantly higher to the infrequent (target) tone compared to the frequent (nontarget) tone in all brain sites in all of the regions of interest time-frequency intervals. Significantly higher ERO energy and significantly lower synchrony was seen in the periadolescent humans and rats compared to their adult counterparts. Taken together these findings are consistent with the hypothesis that adolescent remodeling of the brain includes decreases in energy and increases in synchrony over a wide frequency range both within and between neuronal networks and that these effects are conserved over evolution.


Asunto(s)
Metabolismo Energético/fisiología , Potenciales Evocados Auditivos/fisiología , Estimulación Acústica , Adolescente , Conducta del Adolescente/fisiología , Adulto , Animales , Conducta Animal/fisiología , Niño , Electroencefalografía , Sincronización de Fase en Electroencefalografía , Femenino , Humanos , Masculino , Red Nerviosa/crecimiento & desarrollo , Ratas , Ratas Wistar , Adulto Joven
15.
Clin Neurophysiol ; 125(9): 1774-82, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24560133

RESUMEN

OBJECTIVE: We investigated the neurophysiological mechanisms underpinning the generation of the mismatch negativity (MMN) in the ageing brain. METHODS: We used dynamic causal modelling (DCM) to study connectivity models for healthy young and old subjects. MMN was elicited with an auditory odd-ball paradigm in two groups of healthy subjects with mean age 74 (n=30) and 26 (n=26). DCM was implemented using up to five cortical nodes. We tested models with different hierarchical complexities. RESULTS: We showed that the network generating MMN consisted of 5 nodes that could modulate all intra- and inter-nodal connections. The inversion of this model showed that old subjects had increased input from rSTG to the rIFG (p<0.01) together with increased inhibition of pyramidal cells (p<0.05). Furthermore, there was reduced modulation of activity within rIFG (p<0.02) on stimulus change. CONCLUSION: The age related change in MMN is due to a decline in frontal-based control mechanisms, with alterations in connectivity between temporal and frontal regions together with a dysregulation of the excitatory-inhibitory balance in the rIFG. SIGNIFICANCE: This study provides for the first time a neurobiological explanation for the age related changes of the MMN in the ageing brain.


Asunto(s)
Envejecimiento/fisiología , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiología , Electroencefalografía , Potenciales Evocados Auditivos/fisiología , Estimulación Acústica , Adulto , Anciano , Femenino , Humanos , Masculino , Modelos Neurológicos , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/fisiología , Células Piramidales/fisiología
16.
J Neurosci ; 32(5): 1589-601, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22302801

RESUMEN

Subplate neurons (SPNs) are a population of neurons in the mammalian cerebral cortex that exist predominantly in the prenatal and early postnatal period. Loss of SPNs prevents the functional maturation of the cerebral cortex. SPNs receive subcortical input from the thalamus and relay this information to the developing cortical plate and thereby can influence cortical activity in a feedforward manner. Little is known about potential feedback projections from the cortical plate to SPNs. Thus, we investigated the spatial distribution of intracortical synaptic inputs to SPNs in vitro in mouse auditory cortex by photostimulation. We find that SPNs fell into two broad classes based on their distinct spatial patterns of synaptic inputs. The first class of SPNs receives inputs from only deep cortical layers, while the second class of SPNs receives inputs from deep as well as superficial layers including layer 4. We find that superficial cortical inputs to SPNs emerge in the second postnatal week and that SPNs that receive superficial cortical input are located more superficially than those that do not. Our data thus suggest that distinct circuits are present in the subplate and that, while SPNs participate in an early feedforward circuit, they are also involved in a feedback circuit at older ages. Together, our results show that SPNs are tightly integrated into the developing thalamocortical and intracortical circuit. The feedback projections from the cortical plate might enable SPNs to amplify thalamic inputs to SPNs.


Asunto(s)
Corteza Cerebral/citología , Corteza Cerebral/crecimiento & desarrollo , Red Nerviosa/citología , Red Nerviosa/crecimiento & desarrollo , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Vías Nerviosas/citología , Vías Nerviosas/crecimiento & desarrollo , Estimulación Luminosa/métodos , Tálamo/citología , Tálamo/crecimiento & desarrollo
17.
Curr Biol ; 22(3): 253-8, 2012 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-22264606

RESUMEN

Spontaneous network activity constitutes a central theme during the development of neuronal circuitry [1, 2]. Before the onset of vision, retinal neurons generate waves of spontaneous activity that are relayed along the ascending visual pathway [3, 4] and shape activity patterns in these regions [5, 6]. The spatiotemporal nature of retinal waves is required to establish precise functional maps in higher visual areas, and their disruption results in enlarged axonal projection areas (e.g., [7-10]). However, how retinal inputs shape network dynamics in the visual cortex on the cellular level is unknown. Using in vivo two-photon calcium imaging, we identified two independently occurring patterns of network activity in the mouse primary visual cortex (V1) before and at the onset of vision. Acute manipulations of spontaneous retinal activity revealed that one type of network activity largely originated in the retina and was characterized by low synchronicity (L-) events. In addition, we identified a type of high synchronicity (H-) events that required gap junction signaling but were independent of retinal input. Moreover, the patterns differed in wave progression and developmental profile. Our data suggest that different activity patterns have complementary functions during the formation of synaptic circuits in the developing visual cortex.


Asunto(s)
Red Nerviosa/crecimiento & desarrollo , Corteza Visual/crecimiento & desarrollo , Animales , Colforsina/análogos & derivados , Colforsina/farmacología , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/metabolismo , Uniones Comunicantes/fisiología , Ratones , Red Nerviosa/efectos de los fármacos , Neuronas Retinianas/fisiología , Transmisión Sináptica/efectos de los fármacos , Corteza Visual/efectos de los fármacos , Corteza Visual/fisiología
18.
J Neurosci ; 32(4): 1244-52, 2012 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-22279209

RESUMEN

Circulating hormones influence multiple aspects of hypothalamic development and play a role in directing formation of neural circuits. Leptin is secreted by adipocytes and functions as a key developmental signal that promotes axon outgrowth from the arcuate nucleus (ARH) during a discrete developmental critical period. To determine the cellular mechanisms by which leptin impacts development of hypothalamic circuits, we examined roles for leptin receptor (LepRb) signals in neonatal mice. LepRb, ERK, and STAT3 signaling were required for leptin-stimulated neurite outgrowth from ARH explants in vitro. Neonatal mice with disrupted LepRb→ERK signaling displayed impaired ARH projections but were able to compensate by adulthood. LepRb→STAT3 signaling also plays a role in early circuit formation and controls the ultimate architecture of POMC, but not AgRP, projections. Thus, the developmental actions of leptin on feeding circuits are dependent on LepRb, and distinct signaling pathways are responsible for directing formation of NPY and POMC projections.


Asunto(s)
Conducta Alimentaria/fisiología , Hipotálamo/crecimiento & desarrollo , Red Nerviosa/crecimiento & desarrollo , Receptores de Leptina/fisiología , Transducción de Señal/fisiología , Animales , Animales Recién Nacidos , Humanos , Hipotálamo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Técnicas de Cultivo de Órganos
19.
J Neurosci ; 31(17): 6405-13, 2011 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-21525281

RESUMEN

A number of studies have characterized the changes in variability of brain signals with brain maturation from the perspective of considering the human brain as a complex system. Specifically, it has been shown that complexity of brain signals increases in development. On one hand, such an increase in complexity can be attributed to more specialized and differentiated brain regions able to express a higher repertoire of mental microstates. On the other hand, it can be explained by increased integration between widely distributed neuronal populations and establishment of new connections. The goal of this study was to see which of these two mechanisms is dominant, accounting for the previously observed increase in signal complexity. Using information-theoretic tools based on scalp-recorded EEG measurements, we examined the trade-off between local and distributed variability of brain signals in infants and children separated into age groups of 1-2, 2-8, 9-24, and 24-66 months old. We found that developmental changes were characterized by a decrease in the amount of information processed locally, with a peak in alpha frequency range. This effect was accompanied by an increase in the variability of brain signals processed as a distributed network. Complementary analysis of phase locking revealed an age-related pattern of increased synchronization in the lower part of the spectrum, up to the alpha rhythms. At the same time, we observed the desynchronization effects associated with brain development in the higher beta to lower gamma range.


Asunto(s)
Mapeo Encefálico , Ondas Encefálicas/fisiología , Encéfalo/fisiología , Desarrollo Infantil/fisiología , Detección de Señal Psicológica/fisiología , Estimulación Acústica , Factores de Edad , Encéfalo/anatomía & histología , Niño , Preescolar , Electroencefalografía/métodos , Entropía , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Modelos Neurológicos , Red Nerviosa/crecimiento & desarrollo , Estimulación Luminosa/métodos
20.
Cereb Cortex ; 21(5): 1042-55, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20847153

RESUMEN

The integration of multisensory information is essential to forming meaningful representations of the environment. Adults benefit from related multisensory stimuli but the extent to which the ability to optimally integrate multisensory inputs for functional purposes is present in children has not been extensively examined. Using a cross-sectional approach, high-density electrical mapping of event-related potentials (ERPs) was combined with behavioral measures to characterize neurodevelopmental changes in basic audiovisual (AV) integration from middle childhood through early adulthood. The data indicated a gradual fine-tuning of multisensory facilitation of performance on an AV simple reaction time task (as indexed by race model violation), which reaches mature levels by about 14 years of age. They also revealed a systematic relationship between age and the brain processes underlying multisensory integration (MSI) in the time frame of the auditory N1 ERP component (∼ 120 ms). A significant positive correlation between behavioral and neurophysiological measures of MSI suggested that the underlying brain processes contributed to the fine-tuning of multisensory facilitation of behavior that was observed over middle childhood. These findings are consistent with protracted plasticity in a dynamic system and provide a starting point from which future studies can begin to examine the developmental course of multisensory processing in clinical populations.


Asunto(s)
Envejecimiento/fisiología , Corteza Auditiva/crecimiento & desarrollo , Percepción Auditiva/fisiología , Red Nerviosa/crecimiento & desarrollo , Corteza Visual/crecimiento & desarrollo , Percepción Visual/fisiología , Estimulación Acústica/métodos , Adolescente , Adulto , Envejecimiento/psicología , Corteza Auditiva/anatomía & histología , Mapeo Encefálico/métodos , Niño , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Neocórtex/anatomía & histología , Neocórtex/crecimiento & desarrollo , Red Nerviosa/anatomía & histología , Estimulación Luminosa/métodos , Corteza Visual/anatomía & histología , Adulto Joven
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