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PubMed2005

Critical period for activity-dependent elimination of corticospinal synapses in vitro.

There is no in vitro model of the critical periods for developmental plasticity, the time windows of plastic changes during development, which may hinder in-depth mechanistic analysis. We have shown previously that the corticospinal tract with synaptic connections can be reconstructed in in vitro co-cultures using slices of the sensorimotor cortex and spinal cord of the rat. In our in vitro system, corticospinal synapses form widely over spinal gray matter during early development, after which those on the ventral side are eliminated in an activity and N-methyl-D-aspartate (NMDA)-dependent manner. A detailed quantitative analysis of the time course of sensitivity to an NMDA blocker was made with this system. Synapse distribution was evaluated by recording field excitatory post-synaptic potentials evoked by deep cortical layer stimulation. Corticospinal axon terminal distribution was examined by anterograde labeling with biocytin. We showed that the D-2-amino-5-phosphonovaleric acid (APV) effect is irreversible for at least the length of culture. When APV was removed from the medium before 6 days in vitro(DIV) or after 11 DIV, elimination of ventral synapses was not blocked. APV sensitivity showed a clearly defined time window. A 6-11 DIV application was necessary and sufficient for the full, irreversible block of synapse elimination. From 6-11 DIV, APV sensitivity seems to decrease gradually but not linearly. This system provides an in vitro model of critical periods for developmental plasticity of central synapses which up to now has not been available.

2-Amino-5-phosphonovalerate↗
PubMed1994

Critical period control in sensory cortex.

The search continues for factors whose regulation during development accounts for the end of the critical period for experience-dependent cortical plasticity. Recent studies suggest that NMDA receptors and neurotrophins may be involved either individually or in concert. NMDA receptor subunits are developmentally regulated in a way that affects the kinetic properties of the NMDA receptor. The expression of mRNAs for neurotrophins and their receptors is regulated by developmental factors and by neuronal activity, and exogenous neurotrophins block critical period plasticity in the visual cortex.

Animals↗
PubMed1988

A critical period for long-term potentiation in the developing rat visual cortex.

The in vitro rodent visual cortical slice preparation demonstrates a critical period for long-term potentiation (LTP). Current source density (CSD) analysis reveals peak potentiation of both supra-(layers II-III) and infragranular (layers V) layers of visual cortex during the second postnatal week following stimulation of the subadjacent white matter. By day 30 both the supra- and infragranular CSD sinks show only minimal potentiation. In adults there is no change in supragranular response but infragranular layers reveal 177% potentiation. Therefore, we conclude that rodent visual cortex displays a critical period for maximum plasticity of both supra and infra-granular layers. Supragranular visual cortex plasticity ends by day 30 whereas infragranular layers retain plastic qualities into adulthood.

Aging↗
PubMed1979

A critical period in the development of tectal neurons in the chick, as revealed by early enucleation.

To further study the existence of a critical trophic period in the development of the chick optic tectum, during which the presence of retinal synapses is essential to the continued growth of tectal neurons, we have unilaterally enucleated embryos between stages 14--20 and allowed survival until stages 35--43. If the critical trophic period is between stages 40--44, as previously reported, then we reasoned that early removal of the eye might not have any effect on tectal development until the critical period. We assessed tectal neuron survival by staining for degeneration in the efferent projections of tectal neurons. In early enucleates, degeneration was present from stages 37--43, and the severity of the degeneration was much reduced in comparison to animals enucleated during the critical period. These findings substantiate the proposition that there is a critical period late in chick tectal development. However, because the degeneration in tectal projections is less intense than in animals enucleated during the critical period, we suggest that the early enucleation has permitted axons from the remaining eye to be routed to the deafferented tectum, where they may help to sustain a portion of the tectal neurons through the critical period. Moreover, the somewhat earlier appearance of degeneration in tectal efferent pathways of early enucleates suggests that a subtle trophic relationship between retina and tectum may exist prior to stage 40, even though this relationship is not revealed when enucleations are performed later, as between stages 35--40 (ref. 17).

Age Factors↗
PubMed1978

Interaction of critical periods in the visual cortex of kittens.

The critical period for modifying the preferred direction in cat cortical units occurs earlier than that for monocular deprivation. The independence of the effects of these two types of deprivation from each other was tested by rearing six kittens with both reverse suture and reversed directional deprivation. The kittens were placed in a drum rotating in one direction with one eye open at ages 2 1/2 to 5 weeks; the drum rotation was reversed and the other eye opened when they were 5 to 12 weeks old. Recordings were then made in the visual cortex. The results were the sum of the effects of reverse suture and reversal of directional deprivation: most cells were driven by the eye that was open second, and most unidirectional cells preferred the direction to which the animals were exposed first. Consequently, many unidirectional cells preferred the first direction but were driven by the eye open second--a combination that the animal never saw during rearing. There was also an effect of ocular deprivation on directional properties and vice versa: reverse suture reduced the overall percentage of unidirectional cells, just as directional deprivation has been shown to affect the ocular dominance histogram. This result suggests that the same cells may be affected by both forms of deprivation.

Age Factors↗
PubMed1991

Critical period effects on universal properties of language: the status of subjacency in the acquisition of a second language.

Recent studies have shown clear evidence for critical period effects for both first and second language acquisition on a broad range of learned, language-specific grammatical properties. The present studies ask whether and to what degree critical period effects can also be found for universal properties of language considered to be innate. To address this issue, native Chinese speakers who learned English as a second language were tested on the universal principle subjacency as it applies to wh-question formation in English. Subjects arrived in the U.S.A. between the ages of 4 and 38 years. They were immersed in English for a number of years (a minimum of 5) and were adults at the time of testing. Non-native performance on subjacency was found for subjects of all ages of arrival. Performance declined continuously over age of arrival until adulthood, (r = -.63). When immersion occurred as late as adulthood, performance dropped to levels slightly above chance. In all of the analyses performed, subjacency did not differ from language-specific structures in the degree or manner in which it was affected by maturation. These results suggest that whatever the nature of the endowment that allows humans to learn language, it undergoes a very broad deterioration as learners become increasingly mature.

Adolescent↗
PubMed1995

Characterization of a novel protein regulated during the critical period for song learning in the zebra finch.

A male zebra finch learns a song by listening to a tutor, but song learning is normally restricted to a critical period in juvenile development. Here we identify an RNA whose expression in the song control circuit is altered during this critical period. The RNA encodes a soluble presynaptic protein that forms a predicted amphipathic alpha helix typical of the lipid-binding domain in apolipoproteins. We show this protein, which we call synelfin, to be the homolog of the human non-A beta component (and its precursor) recently purified from Alzheimer's disease amyloid. We suggest this highly conserved protein may serve a novel function critical to the regulation of vertebrate neural plasticity.

Alzheimer Disease↗
PubMed1983

Critical periods in development for susceptibility to the effects of stroboscopic rearing in the rabbit visual cortex.

Previous studies have shown that rearing rabbits in a stroboscopically illuminated environment results in a decrease in orientation and direction selectivity and an increase in responsivity to stroboscopic stimuli among neurons in area 17. In the present study, the critical period for susceptibility to these effects was studied by varying the time of onset of the deprivation. Groups of Dutch belted rabbits were reared normally and then placed in a stroboscopically illuminated environment at ages 1, 2 or 3 months, and response characteristics of visual cortical neurons were compared with those obtained from normal rabbits and from rabbits reared in a stroboscopic environment from birth. Results show that the different effects of strobe rearing have different critical periods. Increased responsivity to stroboscopic stimuli was seen only in rabbits deprived from birth. The effects of strobe rearing on both direction and orientation selectivity decreased with increasing age at the time of onset of the deprivation. However, only direction selectivity was modified by deprivation beginning at 3 months of age.

Age Factors↗
PubMed2007

The critical period hypothesis: can it explain discrepancies in the oestrogen-cognition literature?

Although there is compelling evidence from small randomised controlled trials and cross-sectional studies indicating that oestrogen helps to protect against cognitive ageing in women, the findings of the large, Women's Health Initiative Memory Study failed to support the earlier findings. The attempt to resolve these discrepancies led to the formulation of the Critical Period Hypothesis which holds that oestrogen has maximal protective benefits on cognition in women when it is initiated closely in time to a natural or surgical menopause but not when treatment is begun decades after the menopause. This article reviews the evidence from basic neuroendocrinology, from animal behavioural studies and from human studies that supports the critical period hypothesis. In view of the promise of this hypothesis and its considerable clinical implications, a direct test of its validity is warranted.

Aging↗
PubMed1987

Alcohol teratogenicity in the human: a detailed assessment of specificity, critical period, and threshold.

Though the occurrence of alcohol-related birth defects is well documented in the human and in animal models, definition of specificity, critical period, and dose-response threshold with a precision adequate for clinical risk assessment and management has been lacking. Data from a cohort of 359 neonates, from a large prospective observational study in which chronic alcohol problems and maternal drinking were assessed during pregnancy and standardized neonatal examinations were blinded for prenatal information, were analyzed with the use of multivariate techniques, with uniform control for confounding by eight factors. Craniofacial abnormalities were found to be definitively related to prenatal alcohol exposure in a dose-response manner (p less than 0.001); a significant, but less striking, relationship was observed for other anomalies (p less than 0.01). The critical period for alcohol teratogenicity was confirmed to be around the time of conception. Risk for anatomic abnormalities in the offspring was clearly defined among the 5.6% of infants whose mothers drank more than three ounces of absolute alcohol, that is, more than six drinks, per day. Because of a trend toward an increase in craniofacial abnormalities with increasing embryonic alcohol exposure at lower levels, a clear threshold could not be defined. These are not experimental data and the results should not be overinterpreted. Nevertheless, pending further studies with larger samples, the findings suggest that to completely avoid alcohol-related anatomic abnormalities, advice to discontinue drinking or at least to reduce it to a minimal level before conception is clinically appropriate.

Alcohol Drinking↗
PubMed1996

NGF prevents the changes induced by monocular deprivation during the critical period in rats.

Photic evoked responses were recorded from the striate cortex of Long-Evans hooded intact, monocular visual deprivation (MD) and MD treated with NGF rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provided comparison after binocular photic stimuli between the contralateral and the ipsilateral striate cortex with relation to the MD eye. One month of monocular visual deprivation at the critical period of development resulted in marked reduction of the amplitudes of AVER components as compared to the control recordings (P < 0.001). These changes of the AVER could be prevented by NGF infusion to lateral ventricle at the dosage of 2.0-2.4 micrograms/day for four weeks during the monocular deprivation. In conclusion, the change of AVER amplitudes induced by monocular visual deprivation during the critical period of development can be prevented by NGF infusion to lateral ventricle.

Animals↗
PubMed1995

Refining the estimate of the critical period for susceptibility to enamel fluorosis in human maxillary central incisors.

PURPOSE: The purpose of this study was to determine an improved estimate of the critical period for susceptibility to fluorosis in human maxillary central incisors. METHODS: The fluorosis score, S, of the incisal (I), middle (M), and cervical (C) third divisions on the labial surface of right maxillary central incisors of subjects (a representative sample of 1,085 Hong Kong Chinese children aged 7 to 12 years surveyed in 1986) was determined according to the Chronological Fluorosis Assessment (CFA) Index. Subject data were grouped by month of birth relative to June 1978, when the designated concentration for waterborne fluoride in the community water supply was reduced from 1.0 to 0.7 mg/L. The analytical task was one of finding the correlation maximum in a system of 12 variates and adjustable parameters including the waterborne fluoride concentration, [F-], and the fluorosis score. RESULTS: The main findings were: (1) the peak correlation of S vs [F-] for the male incisal third centered at 17.5 months after birth; (2) and six months later for females; (3) the correlation of S with [F-] is maximized for S(M) following S(I) by two months, and S(C) following S(M) by a further two months for both males and females; and (4) the critical period for exposure to fluoride is of about four months' duration for each third. CONCLUSIONS: The maxillary central incisor, as a whole, appears most at risk to fluorosis from dietary fluoride between age 15 and 24 months for males and between 21 and 30 months for females.

Age Factors↗
PubMed1984

Ontogenesis of muscarinic acetylcholine binding sites in cat visual cortex: reversal of specific laminar distribution during the critical period.

Acetylcholine appears to act as a modulator of neuronal activity in cat visual cortex and, like noradrenaline, may be involved with cortical plasticity mechanisms during the critical period. To explore possible ACh involvement in these mechanisms we have examined acetylcholine binding sites in cat visual cortex during development using [3H]QNB, a muscarinic antagonist. At 3 days postnatal [3H]QNB preferentially labelled binding sites in layer IV. During development the pattern of binding reversed, so that by 95 days postnatal layer IV was the least densely labelled. The number of binding sites increased during development peaking at 1 month postnatal. The Kd of [3H]QNB binding sites increased to 95 days postnatal, with a peak value of 0.76 nM. The results show that during development, and especially within the critical period, changes in [3H]QNB binding site distribution, number and affinity occur.

Animals↗
PubMed1992

Induction of increased testis growth and sperm production in adult rats by neonatal administration of the goitrogen propylthiouracil (PTU): the critical period.

We have previously shown that treating rats with the reversible goitrogen 6-propyl-2-thiouracil (PTU) from birth to Day 25 increases testis size and sperm production in adulthood by up to 80% and 140%, respectively. The purpose of this study was to determine the critical period(s) during development when PTU treatment can increase adult testis size and sperm production. Rats were treated with PTU beginning on Days 0, 8, 16, or 24 for periods of 9, 17, or 25 days. To further define the critical period, additional rats were treated with PTU prenatally or on Days 4-24. PTU treatments of 9, 17, or 25 days beginning at birth increased testis weight 18%, 38%, and 69%, respectively, by 135 days of age, while daily sperm production (DSP) increased 35%, 65%, and 94%, respectively. Efficiency of sperm production (DSP/g testis) also increased by approximately 25% in these rats. There was an inverse relationship between testis and body weights: increasing lengths of PTU treatment increased testis weight but decreased body weight. PTU treatment starting on Day 8 or later did not increase testis weight or DSP regardless of duration. Treatment on Days 4-24 increased adult testis weight and DSP similarly to treatment from birth to Day 24, but prenatal PTU treatment was ineffective. Testosterone concentrations were not altered in treated rats, even those with increased testis weight. These results indicate that the later part of the first postnatal week (Days 4-8) is the crucial period during which PTU treatment must begin in order to increase adult testis size and sperm production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

An epidemiologic estimate of the critical period during which human maxillary central incisors are most susceptible to fluorosis.

The temporal relation between a declining fluorosis gradient and an abrupt downward shift in community drinking water fluoride concentration was evaluated through multiple correlation analysis to determine the critical time frame during which developing maxillary central incisors are most susceptible to fluoride challenge. Fluorosis data were scrutinized through a time-related series of epidemiologic "windows" or time frames of varying lengths. The placement of these time frames was in turn related to the presumed start of enamel mineralization (at birth), and ranged from zero to 60 months later. In this way, the susceptibility of developing enamel to changes in water fluoride concentration was localized. The greatest risk was associated with a four-month critical period commencing at 22 months following birth. The risk of fluorosis from exposures to a fluoride challenge acting during shorter periods was better localized than risk associated with longer exposures. We concluded (1) that human maxillary central incisors are most susceptible to fluorosis during a critical period of as little as four months' duration, commencing at 22 months of age; and (2) that for these incisors, fluoride exposure during the months prior to this period carries less risk than continued exposure for up to 36 months beyond this critical time.

Aging↗
PubMed1989

Critical period for androgenic regulation of soma size of sexually dimorphic motoneurons in rat lumbar spinal cord.

In the rat spinal nucleus of the bulbocavernosus (SNB), androgens are known to act during early critical periods to regulate the number and size of motoneurons that innervate perineal muscles, and to produce sex differences in these attributes. The present study determined the end of the critical period for androgenic regulation of SNB soma size in female rats. Intact female rats received injections of testosterone propionate or oil during 1 of 4 postnatal periods, and were compared to control males and females. In adulthood, all rats were gonadectomized, treated with androgen and then sacrificed. The somatic areas of SNB motoneurons were measured. The results suggest that the soma size is increased by androgen treatment only if it is given before about day 12 after birth.

Aging↗
PubMed1995

A critical period for long-term potentiation at thalamocortical synapses.

In mammalian development, the refinement of topographical projections from the thalamus to the cortex is thought to arise through an activity-dependent process in which thalamic axons compete for cortical targets. In support of this view, if activity is altered during a critical period in early development, normal connectivity is disrupted. It has been proposed that synaptic connections are strengthened during development by correlated pre- and postsynaptic activity, and a likely mechanism for this process would be N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). However, the evidence that LTP is involved in normal development remains inconclusive. We have examined LTP in the thalamocortical synapses that form whisker barrels in rat somatosensory cortex (S1). We report here that the period during which LTP can be induced matches closely the critical period during which the barrels can be modified by sensory perturbations. Moreover, the loss of susceptibility to LTP with age is accompanied by a decrease in NMDA receptor-mediated synaptic currents. These findings provide compelling evidence that LTP is important for the development of cortical circuitry.

Animals↗
PubMed2002

Development of two transmitter release components during the critical period for imprinting in the chick IMHV.

Transmitter release at an excitatory synapse has two components, fast synchronous and slow asynchronous transmitter release. Using the whole cell recording technique, we investigated the developmental properties of neurotransmitter release, which is composed of the two components in the intermediate and medial part of the hyperstriatum ventral (IMHV) of chicks during the critical period for imprinting. Analysis of the paired-pulse responses revealed that the depression of the excitatory postsynaptic currents (EPSCs), driven mainly by fast synchronous release, was frequently observed in P0-1 chicks but not in those at P5-8. The spontaneous excitatory postsynaptic currents (sEPSCs) after the paired-pulse stimulation, which were thought to be driven by asynchronous transmitter releases, were observed more frequently in P0-1 chicks than P5-8 chicks. Furthermore, examination of Ca2+ dependency in the evoked EPSCs showed that the amplitudes in P5-8 chicks were more sensitive to reduction of the extracellular Ca2+ concentration than younger chicks. Considering that the Ca2+ dependency of EPSCs is defined by both Ca2+ sensitivity and the proportion of each type of release machineries at the release site, these results indicate that the ratio of fast synchronous to slow asynchronous transmitter release machinery changed during the critical period. These changes may play critical roles in the capacity of the avian brain to consolidate novel experience in the immediate period after hatching.

Aging↗