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Functional classes of cortical projection neurons develop dendritic distinctions by class-specific sculpting of an early common pattern.

We demonstrate in rat neocortex that the distinct laminar arrangements of the apical dendrites of two classes of layer 5 projection neurons, callosal and corticotectal, do not arise de novo, but are generated later in development from a common tall pyramidal morphology. Neurons of each class initially elaborate an apical dendrite in layer 1. Layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons is actively eliminated, rather than passively displaced, as superficial cortical layers expand. Corticotectal neurons and callosal neurons superficial to layer 5 maintain their apical dendrite to layer 1. Therefore, this selective dendritic loss occurs in a neuron class-specific manner and, within the callosal population, in a lamina-specific manner. Based on our additional observations and other studies, this phenomenon can be extended to other types of cortical projection neurons. These findings show that selective dendritic elimination plays a major role in shaping the functional architecture characteristic of the adult cortex.

Animals↗

Networks of coactive neurons in developing layer 1.

Spontaneous neuronal activity plays an important role in the development of cortical circuitry, yet its spatio-temporal dynamics are poorly understood. Cajal-Retzius (CR) neurons in developing layer 1 are necessary for correct cortical lamination and are strategically located to coordinate early circuit activity. To characterize the spontaneous activity of CR and other layer 1 neurons during cortical development, we imaged calcium transients in populations of layer 1 neurons in hemispheres and slices from postnatal rat somato-sensory neocortex. The spontaneous activity in layer 1 had complex spatio-temporal patterns. Groups of non-CR cells showed synchronous activations and formed networks of correlated neurons superimposed in the same territory. Correlated activity among non-CR cells was mediated by a depolarizing effect of GABA and was modulated by glutamate, probably released by CR cells. Our findings demonstrate that developing layer 1 can sustain complex patterns of correlated activity and reveal a circuit mechanism that can mediate this patterned activity.

Acetylcholine↗

Dynamics of functional connectivity in visual cortical networks: an overview.

The aim of the Royaumont Symposium was to review various dynamic aspects of adaptive changes in functional connectivity, expressed in cortical networks during development, learning, and possibly during recognition and cognitive processing. The link between the various experimental and theoretical models was the comparison of cellular and molecular mechanisms that could be involved in the up- and down-regulation of functional connectivity, over different time scales. These processes have been investigated using several approaches in parallel: 1) at the molecular/subcellular level, to identify postsynaptic receptors (NMDA, mGluR) and second messengers (calcium protein kinases and phosphatases) involved in the induction of synaptic potentiation and depression, and to characterize diffusible factors (NO), released pre- or postsynaptically, involved in the spatial generalization of local changes to neighboring synapses; 2) at the level of integrating networks, to develop electrophysiological (single and multiple recording), pharmacological and optical imaging techniques in order to compare the dynamics of adaptive processes put into play during the natural development of cortical specificity and connectivity, versus those triggered during forced regimes of temporal correlations between pre- and post synaptic activities. Both in vitro and in vivo approaches have been combined in the primary visual cortex of the developing and adult vertebrate (rat, guinea-pig, ferret, cat and monkey). The various forms of 'slow' synaptic plasticity, demonstrated during epigenesis and selective phases of learning in the adult, can be compared with 'fast' forms of functional coupling (or synchronous firing) shown to develop during the time span required for perception and cognitive processing Phenomenology of the dynamics in functional connectivity and their relative dependence on temporal correlation in neuronal activity have been analyzed in each of these situations. Experimental results have been compared at different levels of neuronal integration (synapse, column map and cell assembly) in order to gain a better understanding of functional grouping within cortical networks.

Adaptation, Physiological↗

Development of a cortical visual neuroprosthesis for the blind: the relevance of neuroplasticity.

Clinical applications such as artificial vision require extraordinary, diverse, lengthy and intimate collaborations among basic scientists, engineers and clinicians. In this review, we present the state of research on a visual neuroprosthesis designed to interface with the occipital visual cortex as a means through which a limited, but useful, visual sense could be restored in profoundly blind individuals. We review the most important physiological principles regarding this neuroprosthetic approach and emphasize the role of neural plasticity in order to achieve desired behavioral outcomes. While full restoration of fine detailed vision with current technology is unlikely in the immediate near future, the discrimination of shapes and the localization of objects should be possible allowing blind subjects to navigate in a unfamiliar environment and perhaps even to read enlarged text. Continued research and development in neuroprosthesis technology will likely result in a substantial improvement in the quality of life of blind and visually impaired individuals.

Artificial Intelligence↗

Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: diffusion tensor imaging versus cortical gyration.

This study assessed microstructural development in four regions of the human cerebral cortex during preterm maturation using diffusion tensor imaging (DTI), compared to the macrostructural development of cortical gyration evaluated using three-dimensional volumetric T1-weighted MR imaging. Thirty-seven premature infants of estimated gestational age (EGA) ranging from 25 to 38 weeks were prospectively enrolled and imaged in an MR-compatible neonatal incubator with a high-sensitivity neonatal head coil. Cortical gyration was measured quantitatively as the ratio of gyral height to width on the volumetric MR images in four regions bilaterally (superior frontal, superior occipital, precentral, and postcentral gyri). Mean diffusivity (D(av)), fractional anisotropy (FA-the fraction of D(av) that is anisotropic), and the three DTI eigenvalues (components of diffusivity radial and tangential to the pial surface of cortex) were measured in the same cortical regions. Cortical gyration scores, FA, and radial diffusivity were all significantly correlated with EGA (P < 0.0001). However, in multivariate analysis, no significant relationship (P > 0.05) was found between DTI parameters and cortical gyration beyond their common association with estimated gestational age. Pre- and postcentral gyri had significantly lower anisotropy than the superior occipital and superior frontal gyri (P < 0.05), indicating that DTI is sensitive to regional heterogeneity in cortical development. Maturational changes in the DTI eigenvalues of cortical gray matter were found to differ from those that have previously been described in developing white matter, with a significant age-related decline in the radial diffusivity (P < 0.0001) but not in the tangential diffusivities (P > 0.05).

Algorithms↗

Development of a cortical granule-free area of cortex and the perivitelline space in the hamster oocyte during maturation and following ovulation.

The distribution and behavior of cortical granules (CGs) in hamster oocytes at various stages of maturation were examined using both light (phase-contrast) and electron microscopy. At the germinal vesicle stage, CGs were distributed almost evenly in the cortex of the oocyte. A 'small' CG-free area of the cortex, with prominent cytoplasmic protrusions, appeared twice during the progression of meiosis. The first time, immediately above the metaphase spindle of the first meiosis and secondly, above the metaphase spindle of the second meiosis. Both peripheral migration and exocytosis of CGs appeared to be responsible for the formation of CG-free cortex above the metaphase spindle of first meiosis. The development of CG-free cortex above the metaphase spindle of the second meiosis was definitely due to exocytosis of CGs. The CG-free cortex above the metaphase spindle of the second meiosis increased its size steadily even after the oocytes had been transported into oviducts. Concomitantly, the size of the perivitelline space increased. The enlargement of the perivitelline space in unfertilized oviductal oocytes seems to be attributed not only to the exocytosis of CGs, but also to an extrusion of non-CG materials by the oocytes and perhaps an accumulation of some materials secreted by the oviduct epithelium. The limited (premature) CG-exocytosis during oocyte maturation and prior to fertilization may alter the physico-chemical properties of the zona pellucida slightly in such a way that the zona can be penetrated only by a very 'strong' spermatozoon. The presence of the perivitelline space in the mature oocyte prior to fertilization seems to be essential or at least beneficial to normal fertilization. Distinct cytoplasmic protrusions appear on the cortex above the metaphase spindle. The plasma membrane covering these protrusions seems to represent the membrane synthetized by the oocyte in preparation for the extrusion of polar body.

Animals↗

Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5.

Neurotrophins are candidate molecules for regulating dendritogenesis. We report here on dendritic growth of rat visual cortex pyramidal and interneurons overexpressing 'brain-derived neurotrophic factor' BDNF and 'neurotrophin 4/5' NT4/5. Neurons in organotypic cultures were transfected with plasmids encoding either 'enhanced green fluorescent protein' EGFP, BDNF/EGFP or NT4/5/EGFP either at the day of birth with analysis at 5 days in vitro, or at 5 days in vitro with analysis at 10 days in vitro. In pyramidal neurons, both TrkB ligands increased dendritic length and number of segments without affecting maximum branch order and number of primary dendrites. In the early time window, only infragranular neurons were responsive. Neurons in layers II/III became responsive to NT4/5, but not BDNF, during the later time window. BDNF and NT4/5 transfectants at 10 days in vitro had still significantly shorter dendrites than adult pyramidal neurons, suggesting a massive growth spurt after 10 days in vitro. However, segment numbers were already in the range of adult neurons. Although this suggested a role for BDNF, long-term activity-deprived, and thus BDNF-deprived, pyramidal cells developed a dendritic complexity not different from neurons in active cultures except for higher spine densities on neurons of layers II/III and VI. Neutralization of endogenous NT4/5 causes shorter and less branched dendrites at 10 days in vitro suggesting an essential role for NT4/5. Neutralization of BDNF had no effect. Transfected multipolar interneurons became identifiable during the second time window. Both TrkB ligands significantly increased number of segments and branch order towards the adult state with little effects on dendritic length. The results suggested that early in development BDNF and NT4/5 probably accelerate dendritogenesis in an autocrine fashion. In particular, branch formation was advanced towards the adult pattern in pyramidal cells and interneurons.

Animals↗

The effect of dopamine on adenylate cyclase and Na+,K(+)-ATPase activity in the developing rat renal cortical and medullary tubule cells.

Dopamine has an age-dependent natriuretic and diuretic effect. We have investigated the ontogeny of the dopamine response on adenylate cyclase activity and Na+,K(+)-ATPase activity in two different cell populations in the infant (10-d-old) and the adult (40-d-old) rat kidney. Basal- and forskolin-stimulated adenylate cyclase activity in tubular suspensions of renal cortex was 5.4-fold (p < 0.05) higher in the 10-d-old rats than in the 40-d-old rats but unchanged between the ages in a suspension of medullary tubules. The dopamine-1-specific agonist fenoldopam did not stimulate adenylate cyclase activity in the cortical cells from 10-d-old rats but did stimulate activity 51 +/- 16% (p < 0.05) in the 40-d-old rats. In the medullary suspension, fenoldopam stimulated adenylate cyclase activity by 43.5 +/- 5% (p < 0.001) in the 10-d-old rats and by 32.0 +/- 7% (p < 0.01) in the 40-d-old rats. In the isolated proximal convoluted tubule, dopamine inhibited Na+,K(+)-ATPase activity in both the 10-d-old (34 +/- 3%, p < 0.001) and 40-d-old rats (44 +/- 7%, p < 0.001). In contrast, in the medullary thick ascending limb of Henle, inhibition of Na+,K(+)-ATPase activity by fenoldopam was more pronounced in the 10-d-old (56 +/- 6%, p < 0.001) than in the 40-d-old rat (33 +/- 6%, p < 0.001). In summary, the renal tubular effects of dopamine on adenylate cyclase and Na+,K(+)-ATPase activity change during postnatal development in a cell-specific manner.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development.

Sensory experience is necessary for normal cortical development. This has been shown by sensory deprivation and pharmacological perturbation of the cortex. Because these manipulations affect the cortical network as a whole, the role of postsynaptic cellular properties during experience-dependent development is unclear. Here we addressed the developmental role of somatodendritic excitability, which enables postsynaptic spike timing-dependent forms of plasticity, in rat somatosensory cortex. We used short interfering RNA (siRNA)-based knockdown of Na+ channels to suppress the somatodendritic excitability of small numbers of layer 2/3 pyramidal neurons in the barrel cortex, without altering the ascending sensory pathway. In vivo recordings from siRNA-expressing cells revealed that this manipulation interfered with the normal developmental strengthening of sensory responses. The sensory responsiveness of neighboring cortical neurons was unchanged, indicating that the cortical network was unchanged. We conclude that somatodendritic excitability of the postsynaptic neuron is needed for the regulation of synaptic strength in the developing sensory cortex.

Animals↗

Spontaneous neuronal firing patterns in fetal rat cortical networks during development in vitro: a quantitative analysis.

The development of spontaneous bioelectric activity (SBA) was studied in dissociated occipital cortex cultures prepared from 19 day old rat fetuses. All cultures, recorded one per diem from 5 to 33 days in vitro (div), showed SBA. Computer analysis of 76 extracellularly recorded single unit spike trains was carried out after selection on the basis of stationarity criteria. Statistically significant developmental trends were found in (i) interspike interval dependencies and (ii) fluctuations in mean firing rate, on the order of a minute or longer. The highly dependent firing patterns, including stereotyped bursting, were present mostly in the 9-12 div group, whereas minute-to-minute fluctuations in the intensity of firing were considerably more pronounced in the oldest group (22-33 div) than in the younger cultures. In addition, firing categories defined on the basis of factor-analysis revealed that such fluctuations were almost exclusively to be found in neurons which fired in a pronounced 'burst', rather than a relatively continuous fashion. Only a few mature appearing synaptic structures were observed electron microscopically prior to 12 div, but increased steadily in number thereafter. No cultures prior to 14 div, but all cultures older than this, stained positively for the presence of glutamic acid decarboxylase. An extensive immunoreactive, putative GABAergic, network was present by three weeks in vitro.

Action Potentials↗

Accumulation of different c-erbA transcripts during rat brain development and in cortical neurons cultured in a synthetic medium.

1. Accumulation of different c-erbA transcripts was studied, during rat brain maturation and in cortical neurons differentiating in a serum-free medium, by quantitative Northern blot hybridization. 2. The alpha and beta forms of c-erbA mRNAs exhibit different patterns of accumulation, with a precocious increase in the alpha forms compared with the beta forms both in vivo and in culture. 3. erbA alpha 2 mRNA (2.6 kb) is by far the predominant form, with a maximum at birth (PO). 4. The accumulation patterns of both alpha and beta forms show discrete differences in isolated neurons compared to brain cortices; in particular the pattern of alpha 2 mRNA accumulation in culture suggests its predominant localization to neurons. 5. The presence of T3 in the culture medium does not have significant effects on the level of any of erbA mRNAs. 6. Possible implications and relationships with neuronal terminal differentiation are discussed.

Animals↗

Calcium-dependent [3H]acetylcholine release and muscarinic autoreceptors in rat cortical synaptosomes during development.

A number of presynaptic cholinergic parameters (high affinity [3H]choline uptake, [3H]acetylcholine synthesis, [3H]acetylcholine release, and autoinhibition of [3H]acetylcholine release mediated by muscarinic autoreceptors) were comparatively analyzed in rat brain cortex synaptosomes during postnatal development. These various functions showed a differential time course during development. At 10 days of age the release of [3H]acetylcholine evoked by 15 mM KCl from superfused synaptosomes was Ca2+-dependent but insensitive to the inhibitory action of extrasynaptosomal acetylcholine. The muscarinic autoreceptors regulating acetylcholine release were clearly detectable only at 14 days, indicating that their appearance may represent a criterion of synaptic maturation more valuable than the onset of a Ca2+-dependent release.

Acetylcholine↗

Cortical blindness: an unusual complication after removal of a ganglioneuroma of the neck.

A 5-year-old girl was operated upon after a huge mass had been found on the left side of her neck. Preoperatively the anatomy was studied using MRI, including 3D-reconstruction of the tumor. The left vertebral artery was seen to cross the tumor, and during the operation the vessel was preserved. Postoperatively it thrombosed and a permanent cortical blindness developed. One year later MRI angiography of the intracerebral vessels was performed and a pre-existing anomaly of the circle of Willis was demonstrated, which had contributed to the development of the cortical blindness.

Blindness, Cortical↗