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Critical period for the monocular deprivation effect in rats: assessment with sweep visually evoked potentials.

Rats and mice are the species most frequently used for cellular and biochemical studies of plasticity, but only a few studies have examined developmentally regulated visual plasticity in these species. Here we report a study of the critical period for monocular deprivation in Long-Evans rats in which visual pattern sweep evoked potentials (sweep VEP) was used. Successful recording of sweep VEPs depended on establishing a stable light plane of anesthesia. We found a mixture of halothane and NO2 to be suitable. During a single trial lasting 10 s, anesthetized rats (n = 28) viewed a sinusoidal contrast grating (spatial frequency of 0.13 cycles/deg) that reversed phase at 3 Hz. During the trial, the grating contrast increased logarithmically from 1 to 70%. Extracellular recording pipettes were placed bilaterally in layers II/III of the binocular regions of primary visual cortex. Stimulating the right and left eye on alternate trials, sweep VEP amplitudes were collected for 30 trials from each eye. In monocularly deprived animals, the right eyelid had been sutured for 5 days before recording. Age at suture varied from P19 to P86. In 12 of 13 rats sutured between P19 and P50, the crossed response from the deprived eye was smaller than the crossed response from the nondeprived eye. The same relation prevailed for the uncrossed responses in 11 of 13 animals. There was no significant monocular deprivation effect in animals sutured between P55 and P86 (n = 9). Dark rearing until approximately P90 followed by 5 days of eyelid suture resulted in a strong monocular deprivation effect in both crossed and uncrossed pathways (n = 3). There was little effect of dark rearing alone on the size the sweep VEPs (n = 3). The critical period reported here lasts at least 2 wk longer than reported for rats by Fagliolini et al. and for mice by Gordon and Stryker. Both previous studies used single unit recording rather than the sweep VEP method.

Animals↗

Resolution acuity in astigmats: evidence for a critical period in the human visual system.

Astigmats, who have been fully optically corrected, show an acuity configuration highly characteristic of the uncorrected astigmatism when they are tested with gratings of different orientations. This phenomenon, which is called meridional amblyopia, has been supposed to be neural in origin. This paper attempts to show that there is evidence for a critical period in the visual system of humans. In the experiment described here twelve astigmatic subjects were tested against a control group of six non-astigmatic (emmetropic) subjects. The astigmatic subjects differed in the ages at which they had been initially optically corrected. Square-wave gratings were used to test the subjects and measures of acuity for different orientations were recorded. It was found that those astigmatic subjects corrected above the age of seven showed the usual acuity decrement while those corrected below seven showed significantly smaller meridional amblyopia. The age of seven, therefore, was taken to mark the end of a critical period in the development of the human visual system, after which the system ceases to be structurally influenced by visual input.

Adult↗

The evolution of the critical period for language acquisition.

Evidence suggests that there is a critical, or at least a sensitive, period for language acquisition, which ends around puberty. The existence of this period is explained by an evolutionary model which assumes that (a) linguistic ability is in principle (if not in practice) measurable, and (b) the amount of language controlled by an individual conferred selective advantage on it. In this model, the language faculty is seen as adaptive, favoured by natural selection, while the critical period for language acquisition itself is not an adaptation, but arises from the interplay of genetic factors influencing life-history characters in relation to language acquisition. The evolutionary model is implemented on a computer and simulations of populations evolving under various plausible, if idealized, conditions result in clear critical period effects, which end around puberty.

Adolescent↗

Kittens reared in a unidirectional environment: evidence for a critical period.

1. Kittens were reared in the dark from birth except for a period each day when they were put inside a stationary transparent cylinder, around which a drum with vertical black and white stripes on the inside, rotated in one direction. After the end of the period of exposure, we recorded a sample of single cells from their visual cortices, and analysed each cell for direction and orientation sensitivity and other properties. 2. Two kittens were placed inside the drum, rotating rightward, for 2 hr each seekday from 3 1/2 to 7 weeks of age. A greater proportion of the directionally sensitive cells in their cortices showed a preference for rightward movement. 3. Six other kittens were placed inside the drug for 1 hr each weekday from 2 to 12 weeks of age with the drum rotating leftward up to a particular changeover age, then rightward until 12 weeks. The changeover point occurred at 21, 26, 28, 33, 35 and 51 days for different kittens. A changeover earlier than 4 weeks of age led to a preponderance of cells preferring rightward movement. A changeover later than 5 weeks of age led to a preponderance of cells preferring leftward movement. Comparison of these results with others on monocular deprivation suggests that the peak of the critical period for directional deprivation may occur earlier than the peak of the critical period for monocular deprivation. 4. None of the samples of cells showed a preponderance of cells specific for vertical orientations. It is unclear whether this negative effect resulted from the presence of some horizontal contours during exposure, or some more fundamental cause.

Animals↗

A critical period of transcription required for differentiation of the action potential of spinal neurons.

The early development of excitability of amphibian spinal neurons is characterized by a change from a long Ca2(+)-dependent action potential to a brief Na(+)-dependent impulse. The delayed rectifier K+ current plays a major role in this cell autonomous differentiation. Here we show that the maturation of the delayed rectifier current, and hence the action potential, involves a critical period of mRNA synthesis. It is blocked by inhibition of transcription during an early period of development in culture and fails to develop following removal of the inhibitor and resumption of RNA synthesis. However, the development of an inactivating K+ A-current recovers in these neurons, indicating that some programs of neuronal development are affected during this critical period, while others are spared.

Action Potentials↗

The critical period for repair of CNS of neonatal opossum (Monodelphis domestica) in culture: correlation with development of glial cells, myelin and growth-inhibitory molecules.

A comparison was made of neurite growth across spinal cord lesions in the isolated central nervous system (CNS) of newborn opossums (Monodelphis domestica) at various stages of development. The aim was to define the critical period at which growth after injury ceases to occur, with emphasis on growth-inhibitory proteins, myelin and glial cells. In postnatal opossums 3-6 days old (P3-6), repair was observed 5 days after lesions were made in culture at the cervical level (C7) by crushing with forceps. Through-conduction of action potentials was re-established and axons stained by Dil grew into and beyond the crush. In a series of 66 animals 29 showed repair. In 28 animals at P11-12 with comparable lesions repair was observed in five preparations. At P13-14, the CNS was still viable in culture, but none of the 25 preparations examined showed any axonal growth into the crush or conduction through it. The rostro-caudal gradient of development permitted lesions to be made in mature cervical and immature lumbar regions of P11-12 spinal cord. Growth across crushes occurred in lumbar but not in cervical segments of the same preparation. The development of glial cells and myelin was assessed by electron microscopy and by staining with specific antibodies (Rip-1 and myelin-associated glycoprotein) in cervical segments of neonatal P6-14 opossums. At P8, oligodendrocytes and thin myelin sheaths started to appear followed at P9 by astrocytes stained with antibody against glial fibrillary acidic protein. By P14, astrocytes, oligodendrocytes and well-developed myelin sheaths were abundant. The cervical crush sites of P12 cords contained occasional astrocytes but no oligodendrocytes. Specific antibodies (IN-1) to neurite growth-inhibiting proteins (NI-35/250) associated with oligodendrocytes and myelin in the rat CNS cross-reacted with opossum proteins. Assays using the spreading of 3T3 fibroblasts and IN-1 showed that by P7 inhibitory proteins became apparent, particularly in the hindbrain and cervical spinal cord. The concentrations of NI-35/250 thereafter increased and became abundant in the adult opossum. Our finding of a well-defined critical period, encompassing only 5 days, in CNS preparations that can be maintained in culture offers advantages for analysing mechanisms that promote or prevent CNS repair.

Age Factors↗

The critical period for ethanol effects on cholinergic neuronal expression in neuroblast-enriched cultures derived from 3-day-old chick embryo: NGF ameliorates the cholinotoxic effects of ethanol.

Studies from our laboratory have established that ethanol exerts morphological and biochemical neurotoxic effects during early neuroembryogenesis in the chick brain both in ovo and in culture. In the present study, we further localized the critical period for ethanol effects on cholinergic neuronal expression using neuroblast-enriched cultures derived from 3-day-old chick embryos. Moreover, we report that NGF attenuated the cholinotoxic effects of ethanol. We used the following experimental paradigms: cultures treated with ethanol alone either C0-C3 or C4-C10; NGF alone C0-C4 or C4-C10; ethanol and NGF given concomitantly; ethanol given first then replaced with NGF in the medium; or NGF given first then replaced with ethanol in the medium. The results revealed: (1) the cholinotoxic effect of ethanol occurs between culture days C0 and C4 with day 3 appearing to be most critical; (2) similarly, the critical period for the cholinotoxic effects of NGF is during early neuroblast differentiation, culture days C0-C4; (3) NGF can prevent the cholinotoxic effects of ethanol only if both ethanol and NGF are given concomitantly or if ethanol is given first, then culture is replaced with NGF-containing medium.

Acetylcholine↗

Critical period in muscle spindle regeneration in grafts of developing rat muscles.

Extensor digitorum longus (EDL) muscles from rats at various intervals after birth were grafted into EDL muscles of adult recipients. Three to twelve months after the operation, host muscles containing the grafts were removed and examined for the presence of muscle spindles in the graft. The aim of the study was to establish when muscle spindles become capable of regeneration during development. Regenerated muscles grafted during the first week after birth were virtually spindleless. Grafts of muscles transplanted 10 and 15 days postnatally contained only 5-8 muscle spindles on average. In contrast, the regenerated grafts originating from muscles of 24- and 28-day-old rats were spindle-rich as in mature muscle grafts; the number of spindles in the transplanted EDL muscles (25.0 +/- 2.3; mean +/- SE) attained values comparable to free standard autografts of these muscles in adult animals. Thus, the critical period after grafting, which also involves the loss of a vascular supply, is considerably longer than the critical period for muscle-spindle survival after nerve injury. Fifteen days after birth, when muscle spindles still survive denervation, only a few regenerated spindles were present in the individual muscle regenerates. We assume that the low resistance of immature spindle capsules to ischaemia accounts for their massive degeneration and abortive spindle regeneration in grafts from 10- to 15-day-old rats.

Adenosine Triphosphatases↗

Androgen-specific critical periods for the organization of the major pelvic ganglion.

Previous studies indicate that the major pelvic ganglion (PG) is dependent on testosterone for normal development. Tyrosine hydroxylase (T-OH), DOPA decarboxylase, and choline acetyltransferase (CAT) activities are significantly reduced by postnatal castration on day 10-11, while testosterone replacement therapy reversed all developmental enzyme activity deficits (Melvin and Hamill, 1987). In the present studies castration on the day of birth combined with various testosterone-replacement paradigms produced effects demonstrating that the PG is sensitive to testosterone dosage and time of administration during early postnatal development. Gonadal hormone replacement experiments show that the androgens testosterone and dihydrotestosterone were effective in restoring T-OH and CAT activity deficits produced by neonatal castration. Estrogen therapy reversed the deficits in CAT activity, but was ineffective in reversing the alterations in T-OH activity. Treatment of pregnant dams with the anti-androgen flutamide altered the ontogeny of T-OH and CAT activities in pups despite replacement therapy on the day of birth. Thus, androgen-critical periods exist prenatally as well as postnatally. These studies suggest that the organization of PG development is critically dependent on both the time of exposure and dose of testosterone. Prenatal and postnatal critical periods appear to exist. In addition, the lack of an effect of estradiol on tyrosine hydroxylase activity suggests that androgens are specifically responsible for organizing the noradrenergic development of the PG.

Androgens↗

Cell contact-dependent mechanisms specify taste bud pattern during a critical period early in embryonic development.

After gastrulation, the pharyngeal endoderm is specified to give rise to taste receptor organs without further signaling from other embryonic tissues. We hypothesized that intercellular signaling might be responsible for the specification of taste buds. To test if and when this signaling was occurring, intercellular contacts were transiently disrupted in cultures of pharyngeal endoderm from axolotl embryos, and the number, size, and distribution of taste buds analyzed. Disruption of cell contacts at progressive time points, from neurula to late tail bud stages, revealed a critical period, during mid-tail bud stages, when disruption of cell contacts resulted in a significant increase in taste bud number and size. The spatial distribution of taste buds was also altered; taste buds were more clustered in explants disrupted during the critical period. These effects were not due to general alterations in mitosis and apoptosis. Rather, at least three aspects of taste bud patterning, i.e., number, size, and distribution, are governed by mechanisms dependent on normal cell contacts during a concise time window. Furthermore, our findings are consistent with specification of taste buds by means of lateral inhibitory signaling, which we hypothesize results from cell contact-dependent or short-range diffusible signals.

Ambystoma↗

Critical periods of the mitotic cycle: influence of aminopterin and thymidine on production of chromosomal aberrations by radiation in Crepis capillaris.

The influence of aminopterin (AP), tritiated thymidine ([3H] TdR) and "cold" thymidine (TdR) on production of chromosomal aberrations in meristematic cells of Crepis capillaris irradiated in different stages of the mitotic cycle with 300 rad of 63Co gamma-rays was studied. All the chemical treatments increased most of all the frequency of aberrations induced during two "critical periods" localized before the stage of DNA synthesis (fixation 9 h after irradiation) and before that of mitosis (4 h). Treatments with TdR and [3H]TdR increased most of all the frequency of chromatid aberrations when irradiation was performed in G1, and the frequency of gaps when irradiated in G2. Treatment with AP increased the yield of different types of aberration more uniformly. The modifying effect of the chemicals tested appeared to be independent of replicative synthesis. The "critical periods" are suggested to be the stages when regular "proof reading" and correction of spontaneous errors takes place [9,13]. In addition to this regular mechanism, radiation induces an "emergency" mechanism of repair. AP inhibits the mechanism of regular repair; in addition TdR and [3H] TdR suppress the lateral spread of primary injuries across the chromosome.

Aminopterin↗

Expression of neuroserpin in the visual cortex of the mouse during the developmental critical period.

The neuronal serine protease inhibitor neuroserpin is widely expressed in the developing and adult brain. In the neocortex, neuroserpin is displayed particularly during the period of synaptic specification and refinement, indicating a role as modulator of extracellular proteolytic processes. The synaptic connections of the visual system of the mouse are shaped during early postnatal life by an activity-dependent process. We have studied the expression of the neuronal serine protease inhibitor neuroserpin in the primary visual cortex of mice from birth until the end of the critical period by means of reverse transcription polymerase chain reaction and in situ hybridization. The localization and the level of expression were constant throughout this period. Monocular deprivation with an eyelid sutured induced a decrease in neuroserpin expression in neurons of area 17 after 1 week of deprivation, the decrease being more pronounced on the side contralateral to the closed eye. The expression of neuroserpin in the visual cortex during the critical period and its decrease in parallel to the refinement of synaptic contacts after visual deprivation suggests a regulative role of neuroserpin on these processes.

Age Factors↗

Critical period for retinoic acid-induced developmental abnormalities of the vitreous in mouse fetuses.

To elucidate the underlying developmental mechanisms of persistent hyperplastic primary vitreous (PHPV) in humans, we investigated a mouse model for PHPV induced by retinoic acid. We treated C57BL/6NJcl mice at various stages of pregnancy (gestation days 7, 8, 9, 10, 11, or 12) with the teratogen retinoic acid, which affects the migration of neural crest cells. Untreated pregnant mice served as a control group. The eyes of the fetuses were examined histologically on day 18 on gestation. Developmental abnormalities of the vitreous were defined as the presence of excessive mesenchymal tissue in the vitreous cavity. The incidence of developmental abnormalities of the vitreous in all groups, except for those treated on day 12 of pregnancy, significantly exceeded that in the control group (P<0.01). The histological characteristics of the observed vitreous abnormalities in mice resembled those found in PHPV clinically. Retinoic acid-induced abnormalities in mice can serve as an experimental model for PHPV by environmental factors. Results suggest that the critical period for these retinoic acid-induced abnormalities was during days 7 to 11 of gestation, which corresponds to a critical period of 2.5 to 7 weeks of gestation for PHPV in humans.

Abnormalities, Drug-Induced↗

Critical period programming of intestinal glucose transport via alterations in dietary fatty acid composition.

Intestinal adaptation occurs in response to physiological or pathological processes that include resection, aging, diabetes, radiation, lactation, chronic alcohol feeding, and feeding diets of varying lipid, protein, or carbohydrate composition. The mechanisms involved in the adaptive response include alterations in morphology, cell kinetics, digestive enzyme activity, transport, membrane lipid composition, and enzymes involved in lipid metabolism. This discussion will review the effect of aging and alterations in dietary fatty acid composition on the small intestine. In addition, it may be possible to program the intestinal response to aging by feeding diets of differing fatty acid composition during the critical period of weaning. Alterations in the ratio of polyunsaturated to saturated fatty acids in the diet modifies the age-associated changes in the intestinal uptake of glucose. The changes occur rapidly, progressively, and irreversibly, suggesting that the intestinal uptake of glucose is subject to critical period programming. The mechanism by which diet may modify the ability of the intestine to up- or down-regulate glucose transport requires further investigation.

Animals↗

A critical period for axon regrowth through a lesion in the developing mammalian retina.

Although the central nervous system of mature mammals is incapable of regeneration, certain elements present in the developing system must permit and promote the growth of new axons to their initial targets. We investigate whether the environment of a developing visual system is capable of supporting regeneration in the Brazilian opossum Monodelphis domestica, in which the retinofugal system develops postnatally. Retinae were lesioned up to the 16th postnatal day and analysed for regeneration after a further 7-10 days. Anterograde tracing with Dil showed axons to have regrown from the axotomized area of retina directly through the lesion. Retrograde tracing with horseradish peroxidase injected into the superior colliculus confirmed that axons from the lesioned area of retina had grown to an appropriate position in the midbrain. The proportion of retinae in which axonal continuity was restored across the lesion decreased as the visual system matured, falling to zero after the 12th postnatal day. Thus a critical period exists in the postnatal opossum in which a retinal lesion permits axon passage. Correlating these results to the known pattern of retinofugal pathway development provides an insight into factors that may restrict this critical period to the 12th postnatal day, and suggests that at least some of the axotomized neurons are regenerating.

Animals↗

General theory of critical periods and development of obesity.

The general systems theory (GST), the general theory of organization (GTO), and the general theory of critical periods (GTCP) have been applied to some nutritional problems. This theoretical approach seems to be in good agreement with most of the data of the literature and with the personal experience, pointing at the possibility to use a simple general model to interpret the complex problem of obesity.

Critical Period, Psychological↗

Extension of the critical period for developmental plasticity of the corticospinal pathway.

The corticospinal tract (CST) of the rat undergoes a prolonged period of postnatal development. Lesions of the presumptive CST pathway at birth are followed by the aberrant rerouting of the developing corticospinal axons around the lesion site through adjacent undamaged CNS tissue. This developmental plasticity becomes severely restricted by 5-6 days of age, so the axons are no longer capable of growth around the site of injury. The aim of the current study was to determine whether altering the environment at the site of injury by filling the lesion with transplanted fetal spinal cord tissue could prolong the critical period for developmental plasticity of the corticospinal pathway. The spinal cord was damaged (overhemisection) at three stages in the development of the corticospinal (CS) pathway: 1) prior to the arrival of CS axons, 2) after the axons elongated through the cord but prior to synaptogenesis, and 3) after both axonal elongation and synaptogenesis were completed. One to 9 months later, anterograde neuronal tracing with horseradish peroxidase was used to assess the growth of the corticospinal pathway with or without a fetal transplant at the site of injury, and the pattern of labeling was compared with that observed in adult nonlesioned control animals. Our results indicate that the presence of a transplant prolongs the critical period for developmental plasticity of the CST. Transplants elicited growth of CST axons throughout the postnatal period examined. CST axons damaged prior to synaptogenesis exhibited more robust growth than those lesioned after synaptogenesis had been completed. These results suggest that both environmental and neuronal factors interact to regulate the response of immature CS neurons to injury.

Animals↗

Brain-derived neurotrophic factor overexpression induces precocious critical period in mouse visual cortex.

Brain-derived neurotrophic factor (BDNF) is a candidate molecule for regulating activity-dependent synaptic plasticity on the grounds of its expression pattern in developing visual cortex and that of its receptor, trkB (Castr¿n et al., 1992; Bozzi et al., 1995; Schoups et al., 1995; Cabelli et al., 1996), as well as the modulation of these patterns by activity (Castr¿n et al., 1992; Bozzi et al., 1995; Schoups et al., 1995). Infusing trkB ligands or their neutralizing agents, the trkB-IgG fusion proteins, into visual cortex alters the development and plasticity of ocular dominance columns (Cabelli et al., 1995; Riddle et al., 1995; Galuske et al., 1996 ; Gillespie et al., 1996; Cabelli et al., 1997). To test further the physiological role of BDNF, we studied a transgenic mouse that expresses elevated levels of BDNF in primary visual cortex (V1) postnatally (Huang et al., 1999). We found that unlike the infusion experiments, excess BDNF expressed in mouse visual cortex did not block ocular dominance plasticity. Instead, single neurons in V1 of the BDNF transgenic mice were as susceptible to the effects of monocular deprivation (MD) as neurons in wild-type mice, but only during a precocious critical period. At a time when V1 in the wild-type mouse responded maximally to a 4 d MD with a reduction in its response to deprived eye visual stimulation, the transgenic mouse V1 had already passed the peak of its precocious critical period and no longer responded maximally. This finding suggests a role for BDNF in promoting the postnatal maturation of cortical circuitry.

Animals↗