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Influence of temperature and gonadal steroids on the ontogenetic expression of brain serotonin 1A and 1D receptors during the critical period of sexual differentiation in tilapia, Oreochromis mossambicus.

cDNA sequences of serotonin (5-hydroxytryptamine, 5-HT) 1A and 1D receptors were cloned from the tilapia, Oreochromis mossambicus, brain. The influence of both gonadal steroids and temperature on the ontogenetic expression of brain 5-HT1A and 5-HT1D receptors from days 5 to 15 post-hatch, a critical period of sexual differentiation, was investigated using quantitative real-time reverse transcription-polymerase chain reaction. Neither estrogen nor methyltestosterone had an effect on the ontogenetic expression of 5-HT1A or 5-HT1D receptors. Between days 5 and 10 post-hatch, a critical period for low-temperature-induced feminization, we found no significant difference in the ontogenetic expression of 5-HT1A between exposure to low and elevated temperature. A similar result was found for 5-HT1D. Between days 10 and 15 post-hatch, a critical period for elevated-temperature-induced masculinization, the ontogenetic expression of neither brain 5-HT1A nor 5-HT1D was altered by exposure to elevated temperature. These results suggest that neither brain 5-HT1A nor 5-HT1D plays a critical role in either gonadal steroid- or temperature-induced sexual differentiation.

Aging↗

A critical period for the organization of alternative male phenotypes of tree lizards by exogenous testosterone?

Male tree lizards (Urosaurus ornatus) exhibit permanent adult differences in color and size that are functionally linked with behavioral differences: males with a central blue throat patch are territorial, more aggressive, and smaller than males lacking the patch, who are nomads or satellites foregoing territory defense. Gonadectomy or long-lasting hormone implants in hatchlings affect the development of these permanent adult differences, but similar manipulations in adults are ineffective. Analogous early hormone actions in vertebrate sexual differentiation typically must occur during a critical period. Whether there is a critical period for early hormone actions affecting development of male types in tree lizards is unclear. We followed a protocol identical to our previous experiments on hatchlings, but we manipulated testosterone (T) in later-aged juveniles to determine if they remained sensitive to such hormone manipulations. Testosterone implants given at 60 days posthatching (day 60) did not alter adult throat color, indicating that sensitivity of throat color to T declines by day 60. This contrasts to our earlier work where adult color was affected by T manipulations on day 30. However, size and throat color responded differently to exogenous T, as juveniles given T implants at day 60 grew less than control-implanted males.

Animals↗

A critical period for the recovery of sound localization accuracy following monaural occlusion in the barn owl.

We studied the ability of barn owls to recover accurate sound localization after being raised with one ear occluded. Most of the owls had ear plugs inserted before they reached adult size, and therefore they never experienced normal adult localization cues until their ear plugs were removed. Upon removal of their ear plugs, these owls exhibited large systematic sound localization errors. The rate at which they recovered accurate localization decreased with the age of the bird at the time of plug removal, and recovery essentially ceased when owls reached 38 to 42 weeks of age. We interpret this age as the end of a critical period for the consolidation of associations between auditory cues and locations in space. Owls that had experienced adult localization cues for a short period of time before ear plugging recovered normal accuracy rapidly, even if they remained plugged well past the end of the critical period. This suggests that a brief exposure to normal adult cues early in the critical period is sufficient to enable the recovery of localization accuracy much later in life.

Aging↗

Is intestinal transport of sugars and amino acids subject to critical-period programming?

Physiological responses include three sorts: reversible within an individual's lifetime, fixed irreversibly at some critical period in life, and genetic. Examples of the first and third but not the second sort have been demonstrated for intestinal nutrient transport. Hence, we searched for critical-period programming of sugar and amino acid transport by mouse small intestine. Mice were maintained on either of two rations from gestation through birth, lactation, and weaning until adulthood: a high-carbohydrate, maintenance-protein ration and a carbohydrate-free, high-protein ration. The two groups of mice were then compared in adulthood while both groups were on the former or the latter ration. Early diet has irreversible effects on gut and body size; because of higher growth rates until weaning mice receiving high-carbohydrate diets achieved and maintained higher weights, longer guts, and heavier proximal guts than the mice receiving carbohydrate free diets. This difference increased with litter size and may have arisen from limitations on nursing mothers' ability to convert dietary protein into milk carbohydrate or fat. Early diet appears to exert some general effects on adult intestinal transport as a result of these differences in body and gut size but does not appear to exert specific irreversible effects on transport of D-glucose, L-proline, L-leucine, L-lysine, or L-aspartate or on passive glucose permeability. Active and passive glucose transport increases reversibly on a high-carbohydrate diet, whereas amino acid transport increases reversibly on a high-protein diet.

Amino Acids↗

Can we disentangle life course processes of accumulation, critical period and social mobility? An analysis of disadvantaged socio-economic positions and myocardial infarction in the Stockholm Heart Epidemiology Program.

The accumulation hypothesis would propose that the longer the duration of exposure to disadvantaged socio-economic position, the greater the risk of myocardial infarction. However there may be a danger of confounding between accumulation and possibly more complex combinations of critical periods of exposure and social mobility. The objective of this paper is to investigate the possibility of distinguishing between these alternatives. We used a population based case-control study (Stockholm Heart Epidemiology Programme) of all incident first events of myocardial infarction among men and women, living in the Stockholm region 1992-94. The analyses were restricted to men 53-70 years, 511 cases and 716 controls. From a full occupational history each subject was categorized as manual worker or non-manual at three stages of the life course, childhood (from parent's occupation), at the ages 25-29 and 51-55, resulting in 8 possible socio-economic trajectories. We found a graded response to the accumulation of disadvantaged socio-economic positions over the life course. However, we also found evidence for effects of critical periods and of social mobility. A conceptual analysis showed that there are, for theoretical reasons, only a limited number of trajectories available, too small to form distinct empirical categories of each hypothesis. The empirical task of disentangling the life course hypotheses of critical period, social mobility and accumulation is therefore comparable to the problem of separating age, period, and cohort effects. Accordingly, the interpretation must depend on prior knowledge of more specific causal mechanisms.

Aged↗

Fos expression during the critical period in visual cortex: differences between normal and dark reared cats.

The present study tested further the notion that immediate early gene expression is involved in neuronal plasticity during the critical period of visual cortex (VC) by comparing Fos induction in normal and dark reared (DR) cats. Western blots indicated that the level of induced Fos expression was higher in normal than DR cat VC at 5 weeks of age, comparable at 10 weeks, and higher in DR than normal cat VC at 20 weeks. Immunohistochemistry indicated that at 5 weeks Fos was induced in cells of all VC layers in both rearing conditions, but to a greater extent in normal than DR cats. At 20 weeks, Fos was largely restricted to cells above and below layer IV in both rearing conditions, but was induced to a greater extent in DR than normal cats. Thus, dark rearing appears to have very similar effects on Fos expression as it has on neuronal plasticity during the postnatal critical period.

Animals↗

[Critical periods in the pubertal development of girls].

The authors analyze the results of physical and sexual development of girls at the pubertal period, as well as their blood levels of hormones participating in the growth regulation and characterizing the +hypophyseal-gonadal relations. A staged pattern of pubertal period is emphasized+ and the critical period singled out: the age of menarche onset and establishment of the ovulation cycle (at the age of 14-15).

Adolescent↗

A shift in protein S-palmitoylation, with persistence of growth-associated substrates, marks a critical period for synaptic plasticity in developing brain.

In the mammalian cortex, the initial formation of synaptic connections is followed by a prolonged period during which synaptic circuits are functional, but retain an elevated capacity for activity-dependent remodeling and functional plasticity. During this period, synaptic terminals appear fully mature, morphologically and physiologically. We show here, however, that synaptic terminals during this period are distinguished by their simultaneous accumulation of multiple growth-associated proteins at levels characteristic of axonal growth cones, and proteins involved in synaptic transmitter release at levels characteristic of adult synapses. We show further that newly formed synapses undergo a switch in the dynamic S-palmitoylation of proteins early in the critical period, which includes a large and specific decrease in the palmitoylation of GAP-43 and other major substrates characteristic of growth cones. Previous studies have shown that a similar reduction in ongoing palmitoylation of growth cone proteins is sufficient to stop advancing axons in vitro, suggesting that a developmental switch in protein S-palmitoylation serves to disengage the molecular machinery for axon extension in the absence of local triggers for remodeling during the critical period. Only much later does a decline in the availability of major growth cone components mark the molecular maturation of cortical synapses at the close of the critical period.

Aging↗

Voltage sensitive calcium channels mark a critical period in mouse neurodevelopment.

Voltage sensitive calcium channel (VSCC) probes 125I-omega-GVIA Conotoxin (omega-GVIA), (+)-[5-methyl-3H]-PN200-110 (3H-PN200), and 3H-Nimodipine were bound to developing Swiss Webster mouse whole brain from postnatal days 3 to 24. 125I-omega-GVIA binding, thought to be presynaptic, showed a 50% increase between days 11 and 14. 3H-dihydropyridine binding, thought to be postsynaptic, showed spike patterns when measured developmentally. 3H-PN200 binding showed a > 150% increase between days 11 and 15. 3H-Nimodipine binding showed a > 100% increase between days 11 and 14. Depolarization-induced 45Ca fluxes also increased between days 8 and 16 by > 500%. The dramatic increases indicated by these binding data correspond to a critical period described by Himwich (Int. Rev. Neurobiol. 4, 117, 1962) between postnatal days 11 and 14 in Swiss Webster mice; during this critical period, dendrites exhibit rapid outgrowth, sensory modalities come on line, EEG patterns mature, and the cortex reaches adult proportions. We conclude from these data that the increase in VSCC activity parallels a critical period in the development of the central nervous system in Swiss Webster mice.

Animals↗

The Critical Period for Experience-dependent Plasticity in a System of Binocular Visual Connections in Xenopus laevis: Its Extension by Dark-rearing.

Following surgical rotation of an eye, the Xenopus 'intertectal' system is capable of a vision-dependent alteration of its connectivity, that restores spatial registration of binocular maps on the optic tectum. In the preceding paper (Keating and Grant, Eur. J. Neurosci., 4, 27 - 36, 1992), we reported that this capacity undergoes a progressive, age-dependent restriction during a critical period around the time of metamorphosis, so that rotations produced in animals aged >/=3 months postmetamorphosis normally evoke no such alteration of the system. Here we examine whether this restriction is rigidly age-dependent or whether vision can influence its profile. We report that in animals dark-reared from embryonic stage 35 through the critical period to 3 months, 1 year or even 2 years after metamorphosis, rotations instituted at those ages now result in intertectal reorganization if a period of normal vision is allowed after the operation. Similarly, intertectal alteration was also seen in animals eye-rotated at larval stage 58, then dark-reared just for the duration of the critical period, and subsequently returned, at 3 months of age, to a normal visual environment. We conclude, therefore, that the normal developmental restriction in the plasticity of the Xenopus intertectal system is not strictly age-dependent, but that vision contributes to the process by activating the underlying plasticity mechanisms.

Journal Article↗

A critical period of ventricular fibrillation more susceptible to defibrillation: real-time waveform analysis using a single ECG lead.

Previous studies have suggested that variations in the underlying ventricular fibrillation (VF) waveform may be one of the factors responsible for the probabilistic nature of defibrillation. The heart appeared to be more susceptible to defibrillation at higher absolute VF voltages (AVFV). This study investigated in an open-chest canine model (n = 8), a newly developed system that analyzed the VF waveform in real-time, instantaneously determined the time to shock, and immediately delivered a fixed low energy DC shock. A two parameter tracking technique using a running long-term and short-term AVFV average was devised to automatically identify a high voltage peak area of the VF waveform, which has been hypothesized to represent a critical period susceptible to defibrillation. Using a DC shock estimated at the 50% success level, the performance using this technique in 58 defibrillation trials was compared to the performance of the conventional method of shocking at a fixed time (random shock method) in 62 trials. Patch size, electrode location, and discharge voltage were kept constant while VF duration, transmyocardial resistance (TMR), energy delivered, and AVFV at the point of shock were measured. Shock energy and current, TMR, and VF duration were similar with both shock methods. A significantly higher AVFV was observed for trials performed with the peak shock method (0.66 +/- 0.02 mV) as compared to trials performed with the random shock method (0.25 +/- 0.09 mV) (P < 0.003). Using lead II as the only sensing lead, the success rate was increased in 6 of 8 dogs (75%) with the new method. One animal showed identical performance, and one animal a worse performance. The overall increase in success rate was 24% using a single ECG lead (range 0%-100%; P < 0.04). Our data document that using this algorithm a period of high VF voltage can be detected in real-time. The improved success in the majority of animals supports the hypothesis that a critical period susceptible to defibrillation exists during VF. However, the high AVFV detected using a single ECG lead did not translate to an improved success rate in all animals. This suggests that other factors in addition to the VF voltage measured on a single lead of the ECG are important in characterizing this critical period.

Algorithms↗

[Critical period in the work of the form-inducing apparatus of the lens in chick embryos, detected after chloramphenicol application].

The inhibitor of protein synthesis chloramphenicol (2 mg/egg) was applied to elucidate the critical period in the chicken lens development. Chloramphenicol injected before incubation and at 24, 30 and 48 h of incubation did not prevent the formation of parts in the lens-inducing apparatus (the optic vesicle, and the presumptive lens ectoderm), but the injection at the stage of 24--30 h of incubation resulted, in many survived for 5--7 days of incubation, in lack of the lens. Therefore, it is possible to speak about a disturbance in the activity of the inducing apparatus during the period of determination, or about a critical period of the lens development.

Age Factors↗

Interactions during a critical period inhibit bilateral projections in embryonic neurons.

The anterior pagoda (AP) neurons in the CNS of the medicinal leech are found as homologous pairs in 20 of the 21 midbody ganglia. Each AP is the mirror image of its mate, extending its main axon across the midline of the CNS and eventually into the contralateral body wall, thereby attaining a unilateral pattern of innervation. Certain features of the adult AP morphology are known to arise through interactions among homologs early in development (Gao and Macagno, 1987b), but it is not known whether the contralateral nature of the projection pattern is due to intrinsic "one-sidedness" or rather to cell-cell interactions that inhibit the formation of a second, ipsilateral projection. In the experiments described in this report, we tested the possibility that an AP's contralateral homolog itself inhibits the formation of bilateral projections. One AP was photoablated in the intact embryo early in development and then the response of the remaining AP was examined. We found that an AP can extend bilaterally symmetrical projections when its homolog is missing, but only during a critical period that, interestingly, begins when an AP's interactions with other specific neurons come to an end. To determine whether synaptic communication between AP homologs could be responsible for the timing of this critical period, we recorded electrophysiologically from pairs of embryonic AP neurons. Although no detectable chemical signaling was observed, AP cells were electrically coupled throughout the entire critical period. Further, the junctions between these neurons were permeated by 5-HT, whereas larger molecules such as carboxyfluorescein were impermeant. This dye coupling decreased with age even while electrical coupling persisted, suggesting but not proving that the properties of the gap junctions between AP neurons may also change with time. We conclude that unilateral AP cells possess the intrinsic ability to project bilaterally, but are inhibited from doing so by age-dependent interactions with homologous neurons, possibly mediated by gap-junctional communication.

Aging↗

Critical periods in human growth and their relationship to diseases of aging.

It has long been recognized that there are "critical periods" during mammalian development when exposure to specific environmental stimuli are required in order to elicit the normal development of particular anatomical structures or their normal functioning. The responses of the organism to these stimuli depend on a specific level of anatomical maturation and a state of rapid anatomical and/or functional change. This discussion of critical periods in growth is not confined to the classic definition of a narrow time frame of development during which a particular environmental threshold or limit must exist for normal growth and function to ensue. Using both auxological and epidemiological approaches, we suggest a lifespan perspective which encompasses accumulating and interacting risks that are manifest from prenatal life onward. By understanding the process of growth development, and by scrutinizing the growth process, early variations that lead to later disease can be identified. Here we review a significant amount of the evidence that links exposure during growth to later morbidity and mortality. The fetus appears to respond to insults during the prenatal period through the process of "programming," which has short-term survival advantages but may have a long-term disadvantage in that it is associated with cardiovascular disease, hypertension, type II diabetes, and later obesity. Low birth weight combined with rapid postnatal growth during infancy also appears to be associated, for instance, with later childhood and adult sequelae in terms of glucose tolerance and obesity. Independent of birth weight, the timing of adiposity rebound during mid-childhood also predicts later obesity. The timing, magnitude, and duration of adolescent growth and maturationare associated with critical body composition changes, including the normal acquisition of body fat and bone mineralization. In particular, the acquisition of appropriate peak bone mass is critical in determining the later risk of osteoporosis. A putative causal mechanism linking early growth variation to later chronic disease risk through telomeric attrition is discussed. The obligatory loss of telomeric DNA with each cell division serves as a mitotic clock and marks the rate of growth and repair processes in the cell. Although much more work is required, existing studies support the notion that telomere shortening is not only a clock of cellular division, but also marks relative growth rate, as well as contributing to common degenerative processes of aging through its impact on cellular senescence.

Adipose Tissue↗

[Critical periods in the development of mutants in scute Drosophila melanogaster].

Thermosensitive periods of the development of germs of separate pairs of macrochaetae were studied in two lines of mutation of scute Drosophila melanogaster (y/sc4B and cs7). The experiments have revealed the following three features which had not been observed earlier in similar investigations in other mutants of drosophila: 1) change of thermosensitivity in mutants sc7 in different periods of ontogenesis; 2) different sensitivity in mutants of both lines in different critical periods of the same pair of macrochaetae; 3) discrete sensitivity of separate macrochaetae in mutants of both lines at different stages of oogenesis when there are no germs of these organs yet. The change of penetrability of the mutation of scute for scuttellar macrochaetae in mutants y/sc4B caused by the 90-minute-long heating of larvae on the 4th day of their life (critical period of development) is inherited in 15 observed generations of the maternal line. One may consider these periods of the increased thermosensitivity to be tje periods of stepwise determination of germs of separate pairs of macrochaetae.

Animals↗

[Possibility of affecting the regulation of salt and water uptake in the critical periods of development in rats].

Peculiarities in water and salt (NaCl) appetite were studied in rats under various experimental influences during critical periods of development. When sexual maturation is going on, females consume more salt than males. These sex depending differences may be altered by experimental influences but only during critical periods of development, for instance by injection of androgens into neonatal females or by gonadectomy of males, by premature cessation of rearing, etc. The effects of those early interventions manifest themselves after the termination of sexual maturation.

Age Factors↗

A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

A critical period of protein kinase activity required for the induction of long-term potentiation (LTP) was determined in area CA1 or hippocampal slices using the broad-range and potent protein kinase inhibitors K-252a and staurosporine. As reported previously, K-252a and staurosporine blocked LTP induction when applied before, during, and after high-frequency stimulation (HFS). In contrast, K-252a did not block LTP when applied only before and during HFS and washed out immediately after HFS. K-252a and staurosporine both attenuated LTP magnitude when applied immediately after or as late as 5 min after HFS. However, K-252a applications beginning 30-45 min after HFS did not affect LTP expression significantly. K-252a had no detectable effect on isolated N-methyl-D-aspartate (NMDA) receptor-mediated EPSPs but significantly inhibited the in situ phosphorylation of specific hippocampal proteins (synapsin I, MARCKS, and B-50). In addition, K-252a attenuated 4 beta-phorbol-12,13-dibutyrate (PDBu)-enhanced synaptic transmission. Our results indicate that there is a critical period of protein kinase activity required for LTP induction that extends for approximately 20 min after HFS. In addition, our results suggest that protein kinase activity during and immediately after HFS is not sufficient for LTP induction. These results provide new information about the mechanisms that underlie LTP induction and expression and provide evidence for persistent and/or Ca(2+)-independent protein kinase activity involvement in LTP.

Animals↗

Do NMDA receptor kinetics regulate the end of critical periods of plasticity?

Increasing NR2A subunit expression and the associated shortening of the NMDA-EPSC are thought to underlie the loss of diverse types of sensory cortical plasticity. Lu and colleagues (Lu et al., 2001 [this issue of Neuron]) now report that mice lacking the NR2A subunit display normal duration of critical periods of barrel cortex plasticity. Shortening of the NMDA-EPSC is therefore not responsible for the end of these critical periods.

Animals↗