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PubMed2004

Development of intrinsic properties and excitability of layer 2/3 pyramidal neurons during a critical period for sensory maps in rat barrel cortex.

The development of layer 2/3 sensory maps in rat barrel cortex (BC) is experience dependent with a critical period around postnatal days (PND) 10-14. The role of intrinsic response properties of neurons in this plasticity has not been investigated. Here we characterize the development of BC layer 2/3 intrinsic responses to identify possible sites of plasticity. Whole cell recordings were performed on pyramidal cells in acute BC slices from control and deprived rats, over ages spanning the critical period (PND 12, 14, and 17). Vibrissa trimming began at PND 9. Spiking behavior changed from phasic (more spike frequency adaptation) to regular (less adaptation) with age, such that the number of action potentials per stimulus increased. Changes in spiking properties were related to the strength of a slow Ca(2+)-dependent afterhyperpolarization. Maturation of the spiking properties of layer 2/3 pyramidal neurons coincided with the close of the critical period and was delayed by deprivation. Other measures of excitability, including I-f curves and passive membrane properties, were affected by development but unaffected by whisker deprivation.

Action Potentials↗
PubMed2006

A critical period of progesterone withdrawal precedes menstruation in macaques.

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12-24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked.

Animals↗
PubMed1984

Critical period plasticity for visual function: definition in monocularly deprived rats using visually evoked potentials.

VEPs were used to study the effects of visual deprivation and to define the critical period in the hooded rat. It is shown that monocular deprivation in young animals reduces both the visual acuity and the contrast sensitivity of the deprived eye and that the depth of attenuation depends upon the age at onset of deprivation. This suggests that the critical period is almost over by 6 weeks postnatally. This simple recording technique might be useful in studying amblyopic children and in defining more clearly the critical period for human vision.

Aging↗
PubMed2004

Experience-dependent changes in basal dendritic branching of layer 2/3 pyramidal neurons during a critical period for developmental plasticity in rat barrel cortex.

In rat barrel cortex, development of layer 2/3 receptive fields can be disrupted by sensory deprivation, with a critical period ending around postnatal day (PND) 14. To determine if experience-dependent plasticity of dendritic morphology could contribute to the reorganization of synaptic inputs, we analyzed dendritic structure in acute brain slices using two-photon laser scanning microscopy (2PLSM) and automated segmentation and analysis software. Layer 2/3 pyramidal cells from control and deprived rats were imaged from PND 9 to PND 20, spanning the critical period. Detailed analyses were performed on basal arbors, which receive the majority of synaptic input from layer 4. Some parameters (number of primary dendrites, volume subtended, aspect ratios) were stable, suggesting that development of several important properties of basal arbors has ceased by age PND 9. However, the spatial organization of secondary branching changed with age and experience. In older neurons there was a larger fraction of branch points farther from the soma. Deprivation from age PND 9 delayed these changes in secondary branching. This effect of deprivation was rapid (detectable at PND 10) and present at all ages observed. Deprivation initiated at PND 15 had no effect on basal branching measured at PND 20. Thus the spatial organization of secondary dendritic branching is experience-dependent and shares a critical period with receptive field plasticity.

Adaptation, Physiological↗
PubMed1998

First-language acquisition in adolescence: evidence for a critical period for verbal language development.

It has been hypothesized that there is a critical period for first-language acquisition that extends into late childhood and possibly until puberty. The hypothesis is difficult to test directly because cases of linguistic deprivation during childhood are fortunately rare. We present here the case of E.M., a young man who has been profoundly deaf since birth and grew up in a rural area where he received no formal education and had no contact with the deaf community. At the age of 15, E.M. was fitted with hearing aids that corrected his hearing loss to 35 dB, and he began to learn verbal Spanish. We describe his language development over the 4-year period since his acquisition of hearing aids and conclude that the demonstrates severe deficits in verbal comprehension and production that support the critical period hypothesis.

Adult↗
PubMed1987

The critical period of Purkinje cell degeneration and cerebellar hypoplasia due to bilirubin.

The critical period of Purkinje cell degeneration and cerebellar hypoplasia due to bilirubin was examined in rats with transient hyperbilirubinemia induced by a serial subcutaneous injection of novobiocin from 1 to 3, 5 to 7, 10 to 13, or 16 to 20 days after birth. Animals showing total plasma bilirubin levels of 5 to 7 mg/100 ml 6 h after the final injection were used for this study. In nearly midsagittal sections of the culmen, the percentage of the affected Purkinje cells was 0.9%, 17.1%, 0% and 0% at days 3, 7, 13 and 20, respectively. Thus, the Purkinje cells were most vulnerable to bilirubin between days 5 and 7. Cerebella from the rats which showed transient hyperbilirubinemia at day 3, 7, 13 or 20 were weighed at day 30. The cerebellar weight was significantly low only in rats showing hyperbilirubinemia at day 7. Thus, the critical period of the cerebellar hypoplasia due to bilirubin coincided with the period when the Purkinje cells were most sensitive to bilirubin. These results suggest that the Purkinje cell damage leads to the cerebellar hypoplasia in hyperbilirubinemia.

Aging↗
PubMed1977

Thallium-induced achondroplasia in chicken embryos and the concept of critical periods during development.

Achondroplasia was induced in chicken embryos by in ovo application of 0.6 mg/egg thallium sulfate. The critical (sensitive) period for production of achondroplasia began on day 5 of incubation and ended at the start of HH stage 35 (8.5 days). The end of the critical period was accurately timed and found to be 205-207 hours of incubation and to coincide with a 66% decrease in growth rate of the embryos. Treatment resulted in reduced tibial growth one day later, tibial angulation two days later, and chrondrocytic necrosis four days later. The last was therefore not the cause of the angulation. Tibias were taken from thallium-treated and control donor embryos of various ages and grafted to the chorioallantoic membranes of treated and control host embryos of various ages during and outside the critical period and achondroplastic changes induced in grafted tibias exposed to thallium while on the chorioallantoic membrane. The critical period was extended into day 10 of incubation in such grafted tibias. Tibias maintained for seven days in organ culture were achondroplastic if pretreated with thallium at seven or eight days of incubation but not at ten days. Exposure of as little as 0.5 hour was sufficient to elicit micromelia when the tibias were grafted or organ cultured. Thallium therefore rapidly binds to skeletal tissues during a critical period of embryonic development but this critical period may be extended when tibias are removed from the embryo.

Abnormalities, Drug-Induced↗
PubMed1981

Further evidence of an early critical period in the development of the cat's dorsal lateral geniculate nucleus.

The concept of an early postnatal critical period of development for the lateral geniculate nucleus was assessed by determining in adult cats whether previously established properties of geniculate neurons could be altered by varying the cat's visual experience. The analysis was limited to lamina A1 and the binocular segment of lamina A, and the properties studied were the percentage of physiologically recorded Y-cells and cell soma size. Eleven experimental cats in four groups were studied, and three cats reared normally plus three cats reared with continuous monocular lid suture served as controls. Two cats raised first with monocular suture followed by a prolonged period in adulthood with both eyes open had cell size distributions and Y-cell proportions that were indistinguishable from cats raised with continuous monocular suture. Four cats raised first with one eye sutured underwent a reverse suture procedure in adulthood (i.e., the originally sutured eye opened and the other closed) and were maintained in this fashion for a prolonged period. These cats also had geniculate cell size distributions and Y-cell proportions that were indistinguishable from cats raised with continuous monocular suture. Two cats were raised first with binocular suture followed by a prolonged period in adulthood with one eye opened. Their geniculate cell size distributions and Y-cell proportions showed no effect on the adult monocular deprivation and were indistinguishable from previously published data concerning cats raised with continuous binocular suture. Finally, three normally raised cats underwent a prolonged period of monocular suture in adulthood. Their geniculate cell size distributions and Y-cell proportions showed no effects on the adult monocular deprivation. From these data, we conclude that an early critical period of development occurs for geniculate cell sizes and Y-cell proportions. Adult visual environments, whether normal or abnormal, had no detectable effect on geniculate neurons for these previously developed properties, whether normal or abnormal.

Age Factors↗
PubMed2000

The critical period for caste determination in Bombus terrestris and its juvenile hormone correlates.

The critical period for caste determination and its juvenile hormone (JH III) correlates were studied in Bombus terrestris. Larvae of known age and instar were taken from young colonies, in which they would have been reared as workers, and placed into groups of queenless workers. Under these conditions the critical age for caste determination was 5 days, during the second instar. Endocrine correlates of caste determination were obtained by determining profiles of juvenile hormone titer and juvenile hormone biosynthesis, measured by chiral-specific radioimmunoassay and the in vitro radiochemical assay, respectively. By the middle of the second instar prospective queen larvae had significantly higher rates of juvenile hormone biosynthesis and juvenile hormone titer than prospective worker larvae. Based on the coincidence of timing of both the critical period and the appearance of caste-specific juvenile hormone titer, we suggest that juvenile hormone plays a role in the mechanisms that control caste determination in B. terrestris.

Animals↗
PubMed1983

[Information analysis of neurocytes of various peripheral ganglia, and critical periods of their differentiation].

Calculation of the informatory parameters of entropy and redundancy performed, taking as a base nuclear-cytoplasmic relations of neurocytes in the inferior ganglion of the vagus nerve, in the superior ganglion and in the interorganic ganglia of the respiratory tube, demonstrated certain interconnection of the integral characteristics obtained with some stages of the neuronal morphological differentiation. Periods of an abrupt reduction in the redundant information up to the minimal values which goes in parallel with an increasing entropy on the 2d-4th months of embryogenesis (taking into account heterochronia in the development of various ganglia) are considered as some critical periods in the neuron development when it passes to the stage of growth (the first critical period) and to the stage of maturation (the second critical period). Their existence is regarded in connection with the hierarchical joining of the vascular and neural trophic types of the vegetative ganglia. A supposition is made on a dependence of the specific neuronal differentiation on the epigenetic factors of morphogenesis.

Cell Differentiation↗
PubMed1999

Sensory regulation of immediate-early genes c-fos and zif268 in monkey visual cortex at birth and throughout the critical period.

The postnatal development of ocular dominance columns (ODCs) in monkey visual cortex provides an exquisite model for studying mechanisms of experience-guided neuronal plasticity. While the presence of columns at birth in Old World monkeys is now well established, it remains unclear whether cortical neurons at this early stage are capable of modulating gene expression in response to changing sensory conditions. Using a set of monocular deprivation and stimulation protocols, we examined activity-driven expression of the immediate-early genes (IEGs) c-fos and zif268 during the critical period of development. We observed well-delineated patterns of ODCs produced by sensory regulation of both IEGs throughout the critical period, starting as early as the first postnatal day. The expression levels are similar in layers II/II, IVC and VI throughout development, with no selective decline in the thalamorecepient layer (layer IVC) of adult monkeys. A narrow strip of non-columnar c-Fos expression was observed at the border of layers IVC and V. Our results show that neurons in monkey visual cortex are equipped at birth with the molecular machinery for coupling sensory inputs to active genomic responses and that this responsivity extends throughout the critical period. The findings are discussed within the context of a possible role for IEGs in sensory-driven cortical plasticity during development.

Animals↗
PubMed1995

Visual deprivation at the critical period modulates photic evoked responses.

Average visual evoked responses (AVER) were recorded from the striate cortex of normal (control) and monocular visually deprived Long-Evans hooded rats. One month of monocular visual deprivation (MD) at the critical period of development resulted in marked reduction of all the three AVER components (i.e., components P2, N2 and P3) as compared to the control recording (P < 0.001). In control animals, the AVER amplitudes of the two hemispheres were identical, while in MD rats, the P2 and N2 components of the AVER obtained from the hemisphere ipsilateral to the MD eye were markedly smaller than those of the AVER obtained from the contralateral hemisphere (P < 0.001). The latencies of the late components (N2 and P3) obtained from the hemisphere ipsilateral to the MD eyes were significantly delayed as compared to those from the contralateral hemisphere (P < 0.05 for N2, P < 0.01 for P3). The AVER following paired photic stimuli with various time intervals between the stimuli were used to study the neuronal recovery function of control animals compared to MD animals. The AVER to the second stimulus obtained from the MD rats exhibited greater attenuation in their amplitude responses than the AVER obtained from the control group, i.e., slower neuronal recovery. The neurophysiological changes observed in this study may relate to the neurocytological alteration occurring in the striate cortex following monocular visual deprivation at the critical period. In conclusion, AVER recorded from monocular visually deprived rats during the critical period is a simple and reliable electrophysiological animal model to study neuroplasticity during postnatal development.

Animals↗
PubMed1976

[Critical periods in the development of spurs in light of the theory of phylembryogenesis].

Two critical periods have been established in the development of spurs representing a derivative of the corneous squama. During the first period the exposure to x-rays results in the development of the corneous squama instead of the spur, and the same exposure during the second critical period completely suppresses the development of the spur. These periods seem to correspond to the truning-points in the chain of morphogenetical processes of the spur formation associated with phylembryogeneses. Department of Embryology, Institute of Experimental Medicine, USSR Acad. Med. Sci., Leningrad.

Animals↗
PubMed2005

Using thermal units for estimating critical period of weed competition in off-season maize crop.

Brazilian off-season maize production is characterized by low yield due to several factors, such as climate variability and inadequate management practices, specifically weed management. Thus, the goal of this study was to determinate the critical period of weed competition in off-season maize (Zea mays L.) crop using thermal units or growing degree days (GDD) approach to characterize crop growth and development. The study was carried out in experimental area of the University of São Paulo, Brazil, with weed control (C), as well as seven coexistence periods, 2, 4, 6, 8, and 12 leaves, flowering, and all crop cycle; fourteen treatments were done. Climate data were obtained from a weather station located close to the experimental area. To determine the critical period for weed control (CPWC) logistic models were fitted to yield data obtained in both W and C, as a function of GDD. For an arbitrary maximum yield loss fixed in 2.5%, the CPWC was found between 301 and 484 GDD (7-8 leaves). Also, when the arbitrary loss yield was fixed in 5 and 10%, the period before interference (PBI) was higher than the critical weed-free period (CWFP), suggesting that the weeds control can be done with only one application, between 144 and 410 GDD and 131 and 444 GDD (3-8 leaves), respectively. The GDD approach to characterize crop growth and development was successfully used to determine the critical period of weeds control in maize sown off-season. Further works will be necessary to better characterize the interaction and complexity of maize sown off-season with weeds. However, these results are encouraging because the possibility of the results to be extrapolated and because the potential of the method on providing important results to researchers, specifically crop modelers.

Agriculture↗
PubMed2001

Timing of excessive ultraviolet radiation and melanoma: epidemiology does not support the existence of a critical period of high susceptibility to solar ultraviolet radiation- induced melanoma.

BACKGROUND: The existence of a 'critical period' early in life characterized by a high susceptibility to melanoma initiation due to excessive ultraviolet (UV) radiation has been suggested by various authors based on epidemiological findings from migration studies and some case-control studies. However, the evidence so far is controversial as several epidemiological investigations failed to corroborate these results. Objective To compare the increase in melanoma risk due to excessive UV radiation between different periods in life. METHODS: In a multicentre case-control study we recruited 603 melanoma cases and 627 population controls in seven European countries. We obtained data on the history of sunburns during 'childhood' (</= 15 years) and 'adulthood' (> 15 years), respectively, in standardized personal interviews. We employed logistic regression analyses to estimate the impact of the exposure factors under study, while simultaneously controlling for the effect of a variety of confounding variables. RESULTS: We found a very similar upward gradient of melanoma risk in exposure categories related to the frequency of sunburns during both periods in life. More than five sunburns doubled the melanoma risk, irrespective of their timing in life. CONCLUSIONS: Our data do not provide supporting evidence for the existence of a 'critical period'. The hazardous impact of sunburns seems to persist lifelong and thus activities concerned with melanoma prevention should be directed to the entire population rather than being focused only on younger age groups.

Adolescent↗
PubMed2003

Rapid critical period induction by tonic inhibition in visual cortex.

Mice lacking a synaptic isoform of glutamic acid decarboxylase (GAD65) do not exhibit ocular dominance plasticity unless an appropriate level of GABAergic transmission is restored by direct infusion of benzodiazepines into the brain. To better understand how intracortical inhibition triggers experience-dependent changes, we dissected the precise timing requirement for GABA function in the monocular deprivation (MD) paradigm. Diazepam (DZ) or vehicle solution was infused daily before and/or during 4 d of MD in GAD65 knock-out mice. Extracellular single-unit recordings from the binocular zone of visual cortex were performed at the end of deprivation. We found that a minimum treatment of 2 d near the beginning of MD was sufficient to fully activate plasticity but did not need to overlap the deprivation per se. Extended delay after DZ infusion eventually led to loss of plasticity accompanied by improved intrinsic inhibitory circuit function. Two day DZ treatment just after eye opening similarly closed the critical period prematurely in wild-type mice. Raising wild-type mice in complete darkness from birth delayed the peak sensitivity to MD as in other mammals. Interestingly, 2 d DZ infusion in the dark also closed the critical period, whereas equally brief light exposure during dark-rearing had no such effect. Thus, enhanced tonic signaling through GABA(A) receptors rapidly creates a milieu for plasticity within neocortex capable of triggering a critical period for ocular dominance independent of visual experience itself.

Animals↗
PubMedDate not supplied

[Intestinal microbiocenosis at the critical periods of child development].

The bacteriological study of fecal specimens obtained from 595 children at different critical periods of the development of their immune system was carried out. The comparison of intestinal microflora in children at the critical periods of the development of their immune system revealed that in children under 1 year considerable changes in the microflora composition were observed during the first 6 months of life. These changes, most pronounced in children aged 1 month and 3-6 months, were characterized by decreased level of indigenous microflora and an increase in the qualitative and quantitative content of aerobic microflora with the representatives of the family Enterobacteriaceae playing the dominating role. In boys such disturbances were manifested to a greater extent than in girls.

Adolescent↗
PubMed2004

Critical period for a teratogenic VLA-4 antagonist: Developmental effects and comparison of embryo drug concentrations of teratogenic and non-teratogenic VLA-4 antagonists.

BACKGROUND: Integrins such as VLA-4 (Very late antigen 4, integrin alpha4beta1) play key roles in cell-cell interactions that are critical for development. Homozygous null knockouts of the VLA-4 alpha4-subunit or VCAM-1 (VLA-4 cell surface ligand) in mice result in failure of the allantois and chorion to fuse leading to interrupted placentation and cardiac development and embryo lethality. Embryo-fetal studies of three VLA-4 antagonists, IVL745, IVL984, and HMR1031 [Crofts et al., Birth Defects Res B 71:55-68 (this issue), 2004] with exposure on gestation days (GD) 6-17 (rat), 6-18 (rabbit) or 6-15 (mouse) showed that only IVL984 treatment resulted in embryo lethality and cardiac defects. Objectives of the current study were to determine the critical period for inducing IVL984-related embryo-fetal effects, and to test the hypothesis that these effects were due to higher embryo drug concentrations. METHODS: IVL984 was administered at 40 mg/kg/day to pregnant rats on GD 4 and 5, GD 6 and 7, GD 8 and 9, GD 10 and 11, or GD 12 and 13. Animals were euthanized on GD 21 and uteri and fetuses were examined. A treatment period of GD 10-12 was selected for subsequent toxicokinetic (TK) studies in which IVL984, HMR1031, or IVL745 was administered to pregnant rats and rabbits. On GD 12, maternal plasma, extra-embryonic tissue (placenta and amniotic fluid), and embryonic tissue were collected and analyzed for drug concentrations. RESULTS: In the IVL984 critical period study in pregnant rats, treatment on GD 10 and 11 resulted in increased post-implantation loss, skeletal variations, and spiral septal defects similar to those observed in standard embryo-fetal development studies with treatment throughout organogenesis. There were no embryo-fetal effects after treatment on GD 4 and 5, GD 6 and 7, or GD 8 and 9. There was a single aorta malformation after treatment on GD 12 and 13. In the TK studies, IVL745, HMR1031, and IVL984 were all detectable in embryonic tissue and there was no evidence for accumulation. Rat and rabbit embryo exposures (AUC or dose-adjusted AUC) on GD 12 could not explain the observed teratology (IVL984<HMR1031<IVL745). Further analyses incorporating pharmacological activity, clearance, and protein binding data provided a positive correlation between embryonic exposure and teratogenic potency. CONCLUSIONS: The critical period for IVL984 in the rat, GD 10 to 11, corresponds to the expression of alpha-4 integrin on the chorion and VCAM-1 on the allantois and myocardium as well as chorioallantoic fusion and formation of the spiral septum. Embryo drug levels adjusted for pharmacological activity, clearance, and protein binding provide a possible explanation for the differing teratogenic potency of IVL984, HMR1031, and IVL745.

Abnormalities, Drug-Induced↗