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PubMed1992

Identification of a critical period for motor development in neonatal rats.

Manipulation of the developing nervous system has provided valuable insights into nervous system function. One important concept to arise from this type of study has been the identification of specific "critical periods" for the development of various functions. A critical period has been most clearly shown for the visual system where monocular eye closure for a few weeks led to functionally significant changes in visually guided behaviors and the connectivity of the visual cortex. Critical periods have also been defined for other sensory systems. Although studies of the effect of manipulating sensory systems during development are sometimes difficult to interpret (e.g. Ref. 7), this difficulty is compounded in the case of the motor system. Problems arise because manipulations of the postnatal motor system are difficult to implement and usually require invasive procedures such as tenotomy, neurotomy, and nerve crush (for review, see Ref. 17). We have approached the problem of manipulating the motor environment by adapting a paradigm widely used to study the experimental effects of simulated weightlessness in adult rats: namely, tail suspension. This method has several advantages for manipulating the motor system: (i) because it is noninvasive, it is less discomforting than neurotomy, tenotomy or nerve crush; (ii) it does not immobilize the animals, they move about the cage and extend and flex their hindlimbs; and (iii) it specifically examines the importance of load-bearing on the development of antigravity muscles and their neuronal circuits.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1999

The critical period for ocular dominance plasticity in the Ferret's visual cortex.

Microelectrode recordings and optical imaging of intrinsic signals were used to define the critical period for susceptibility to monocular deprivation (MD) in the primary visual cortex of the ferret. Ferrets were monocularly deprived for 2, 7 or >14 d, beginning between postnatal day 19 (P19) and P110. The responses of visual cortical neurons to stimulation of the two eyes were used to gauge the onset, peak, and decline of the critical period. MDs ending before P32 produced little or no loss of response to the deprived eye. MDs of 7 d or more beginning around P42 produced the greatest effects. A rapid decline in cortical susceptibility to MD was observed after the seventh week of life, such that MDs beginning between P50 and P65 were approximately half as effective as those beginning on P42; MDs beginning after P100 did not reduce the response to the deprived eye below that to the nondeprived eye. At all ages, 2 d deprivations were 55-85% as effective as 7 d of MD. Maps of intrinsic optical responses from the deprived eye were weaker and less well tuned for orientation than those from the nondeprived eye, with the weakest maps seen in the hemisphere ipsilateral to the deprived eye. Analysis of the effects of 7 d and longer deprivations revealed a second period of plasticity in cortical responses in which MD induced an effect like that of strabismus. After P70, MD caused a marked loss of binocular responses with little or no overall loss of response to the deprived eye. The critical period measured here is compared to other features of development in ferret and cat.

Aging↗
PubMed2006

Identification of disabled-1 as a candidate gene for critical period neuroplasticity in cat and mouse visual cortex.

Rearing in darkness slows the time course of the critical period in visual cortex, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, whereas at 20 weeks dark-reared cats are more plastic [G. D. Mower (1991)Dev. Brain Res., 58, 151-158]. Thus, a stringent criterion is that genes that are important for plasticity in visual cortex will show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young vs. older animals. The present study reports the identification by differential display PCR of Dab-1, the mammalian homolog of the drosophila disabled-1 gene, as a candidate gene for critical period neuronal plasticity, expression of which is regulated according to this criterion in cat visual cortex. Evidence for this bidirectional direction regulation is extended to Dab-1 protein in cat and mouse visual cortex and shown to be specific to visual cortex, not occurring in frontal cortex. The Reelin/Dab-1 pathway has well-documented functions in cell migration during prenatal life and increasing evidence indicates that in postnatal brain the pathway plays a role in synaptic plasticity. The present results extend this evidence by directly implicating Dab-1 in postnatal critical period plasticity of visual cortex.

Animals↗
PubMed1985

Critical periods during development as assessed by thallium-induced inhibition of growth of embryonic chick tibiae in vitro.

In ovo application of thallium sulfate has been shown to produce a characteristic shortening and angulation of the tibia of the embryonic chick. The critical period for susceptibility to thallium-induced inhibition of tibial growth ends at 8 2/3 days of incubation, a time when the growth rate of the embryo declines by 55%. The aim of the present study was to expose tibiae to thallium in vitro to determine whether this response was intrinsic to the tibia. A 4-hour exposure to 400 micrograms thallium was found to be most effective. Growth of tibiae from 8-day-old embryos was inhibited, growth of tibiae from 9-day-old embryos was not, and the response of tibiae isolated from embryos of 8 2/3 days of incubation was intermediate. Therefore, the response of the tibia to thallium represents an intrinsic property and is not secondary to inhibited nerve growth as has been suggested. The critical period and its termination is also an intrinsic property of the tibia. Tibiae were exposed to thallium for 4 hours at various times after the tibiae had been established in vitro. Susceptibility to growth inhibition was shown to decline as tibiae developed beyond the critical period, a decline that could be correlated with a declining growth rate. Emphasis is placed upon critical events during development as a more useful concept than critical periods for explaining susceptibility to teratogens.

Age Factors↗
PubMedDate not supplied

Afferent regulation of neuron number in the cochlear nucleus: cellular and molecular analyses of a critical period.

The neurons of the cochlear nucleus are dependent on input from the auditory nerve for survival during a critical period of development in a variety of vertebrate species. The molecules that underlie this age-dependent vulnerability to deafferentation are for the most part unknown, although recent studies have begun to yield interesting candidate genes. Here, we review the studies that originally described the presence of afferent dependent neuron survival in the cochlear nucleus and the age-dependency of this effect, as well as more recent work that seeks to understand the mechanisms underlying the neuron loss that occurs and the basis of this critical period. While much of the past work on cochlear nucleus neuronal susceptibility has been conducted looking at one or two genes at a time, recent advances in genomics make it possible to screen tens of thousands of genes while looking for candidate genes that are determinants of the critical period response to afferent deprivation.

Afferent Pathways↗
PubMed1984

Critical periods for functional and anatomical compensation in lateral suprasylvian visual area following removal of visual cortex in cats.

Previous experiments have found that neurons in the cat's lateral suprasylvian (LS) visual area of cortex show functional compensation following removal of visual cortical areas 17, 18, and 19 on the day of birth. Correspondingly, an enhanced retino-thalamic pathway to LS cortex develops in these cats. The present experiments investigated the critical periods for these changes. Unilateral lesions of areas 17, 18, and 19 were made in cats ranging in age from 1 day postnatal to 26 wk. When the cats were adult, single-cell recordings were made from LS cortex ipsilateral to the lesion. In addition, transneuronal autoradiographic methods were used to trace the retino-thalamic projections to LS cortex in many of the same animals. Following lesions in 18- and 26-wk-old cats, there is a marked reduction in direction-selective LS cortex cells and an increase in cells that respond best to stationary flashing stimuli. These results are similar to those following visual cortex lesions in adult cats. In contrast, the percentages of cells with these properties are normal following lesions made from 1 day to 12 wk of age. Thus the critical period for development of direction selectivity and greater responses to moving than to stationary flashing stimuli in LS cortex following a visual cortex lesion ends between 12 and 18 wk of age. Following lesions in 26-wk-old cats, there is a decrease in the percentage of cells that respond to the ipsilateral eye, which is similar to results following visual cortex lesions in adult cats. However, ocular dominance is normal following lesions made from 1 day to 18 wk of age. Thus the critical period for development of responses to the ipsilateral eye following a lesion ends between 18 and 26 wk of age. Following visual cortex lesions in 2-, 4-, or 8-wk-old cats, about 30% of the LS cortex cells display orientation selectivity to elongated slits of light. In contrast, few or no cells display this property in normal adult cats, cats with lesions made on the day of birth, or cats with lesions made at 12 wk of age or later. Thus an anomalous property develops for many LS cells, and the critical period for this property begins later (between 1 day and 2 wk) and ends earlier (between 8 and 12 wk) than those for other properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed2001

Model-supported estimation of mortality rates in Baltic cod (Gadus morhua callarias L.) larvae: the varying impact of 'critical periods'.

BACKGROUND: Changes in the survival-rate during the larval phase may strongly influence the recruitment level in marine fish species. During the larval phase different 'critical periods' are discussed, e.g. the hatching period and the first-feeding period. No such information was available for the Baltic cod stock, a commercially important stock showing reproduction failure during the last years. We calculated field-based mortality rates for larval Baltic cod during these phases using basin-wide abundance estimates from two consecutive surveys. Survey information was corrected by three dimensional hydrodynamic model runs. RESULTS: The corrections applied for transport were of variable impact, depending on the prevailing circulation patterns. Especially at high wind forcing scenarios, abundance estimates have the potential to be biased without accounting for transport processes. In May 1988 mortality between hatch and first feeding amounted to approximately 20% per day. Mortality rates during the onset of feeding were considerably lower with only 7% per day. In August 1991 the situation was vice versa: Extremely low mortality rates of 0.08% per day were calculated between hatch and first feeding, while the period between the onset of feeding to the state of an established feeder was more critical with mortality rates of 22% per day. CONCLUSIONS: Mortality rates during the different proposed 'critical periods' were found to be highly variable. Survival rates of Baltic cod are not only influenced by a single 'critical period', but can be limited at different points during the larval phase, depending on several biotic and abiotic factors.

Animals↗
PubMed2000

Inhibitory threshold for critical-period activation in primary visual cortex.

Neuronal circuits across several systems display remarkable plasticity to sensory input during postnatal development. Experience-dependent refinements are often restricted to well-defined critical periods in early life, but how these are established remains mostly unknown. A representative example is the loss of responsiveness in neocortex to an eye deprived of vision. Here we show that the potential for plasticity is retained throughout life until an inhibitory threshold is attained. In mice of all ages lacking an isoform of GABA (gamma-aminobutyric acid) synthetic enzyme (GAD65), as well as in immature wild-type animals before the onset of their natural critical period, benzodiazepines selectively reduced a prolonged discharge phenotype to unmask plasticity. Enhancing GABA-mediated transmission early in life rendered mutant animals insensitive to monocular deprivation as adults, similar to normal wild-type mice. Short-term presynaptic dynamics reflected a synaptic reorganization in GAD65 knockout mice after chronic diazepam treatment. A threshold level of inhibition within the visual cortex may thus trigger, once in life, an experience-dependent critical period for circuit consolidation, which may otherwise lie dormant.

Aging↗
PubMed2005

Early alcohol exposure impairs ocular dominance plasticity throughout the critical period.

Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

Action Potentials↗
PubMed1977

Comparison of the critical periods for monocular and directional deprivation in cats.

1. Earlier experiments rearing kittens with one eye closed and reversing the closure after a certain age, or rearing kittens in a rotating drum and reversing the direction after a certain age, suggest that the critical periods for ocular dominance and directional sensitivity may differ. Since these results were obtained by different investigators in different laboratories, we have made a direct comparison of the two types of visual deprivation. 2. Four pairs of litter-mate kittens (matched in weight) were reared. One animal in each pair was monocularly deprived with subsequent eye reversal; the other animal was directionally deprived with reversal of drum direction. All reversals took place at age 5 weeks. Both kittens in a given pair were either 'left first' (left eye open first or left direction first) or both were right first. One died prematurely. 3. Recordings were made from the visual cortex at some age after 4 months. Some recordings were made in the left cortex and some in the right. In all cases of monocular deprivation, the majority of cells were driven by the eye that was open last (i.e. open after 5 weeks of age). In all cases of directional deprivation, the majority of the cells preferred movement in the first direction of exposure (i.e. the direction before 5 weeks of age). 4. We conclude that the critical period for directional deprivation terminates earlier than the critical period for monocular deprivation.

Animals↗
PubMed1998

Early intervention in psychosis. The critical period hypothesis.

BACKGROUND: We consider the evidence for the proposition that the early phase of psychosis (including the period of untreated psychosis) is a critical period in which (a) long-term outcome is predictable, and (b) biological, psychological and psychosocial influences are developing and show maximum plasticity. METHOD: First-episode prospective studies, predictors of outcome and the genesis of patients' key appraisals of their psychosis are reviewed. RESULTS: The data support the notion of the 'plateau effect', first coined by Tom McGlashan, which suggested that where deterioration occurs, it does so aggressively in the first 2-3 years; and that critical psychosocial influences, including family and psychological reactions to psychosis and psychiatric services, develop during this period. CONCLUSIONS: The early phase of psychosis presents important opportunities for secondary prevention. We outline a prototype of intervention appropriate to the critical period. The data challenge the widely held assumption that first-episode psychosis is a benign illness posing little risk.

Adaptation, Psychological↗
PubMed2004

Specialization of primary auditory cortex processing by sound exposure in the "critical period".

Environmental acoustic exposure to a complex tone sequence within the critical period in infant rats resulted in the emergence of large-scale, selective changes that radically altered primary auditory cortex (A1) organization. In the sound exposure-revised A1, responses were segregated into two explicit zones representing spectrally and temporally separated lower and higher frequency tone sequence progressions. Cortical neurons between these two A1 zones were poorly driven by sound stimuli. Stimulus sequence-specific ("combination-selective") responses emerged in the A1 of exposed rats. These selective representational changes induced in the critical period persisted into adulthood. These results show that the temporal order and pace of early, repetitive postnatal auditory inputs strongly affect the emergent and enduring functional organization of A1.

Animals↗
PubMed2006

Pre- and post-critical period induced reduction of Cat-301 immunoreactivity in the lateral geniculate nucleus and visual cortex of cats Y-blocked as adults or made strabismic as kittens.

PURPOSE: To test the post-critical period stability of perineuronal nets by comparing the expression of antigens on aggrecan (a chondroitin sulfate proteoglycan (CSPG) recognized by the monoclonal antibody Cat-301) in the lateral geniculate nucleus (LGN) and striate cortex (A17) of adult Y-blocked cats and cats made strabismic and amblyopic as kittens. The comparison tested the idea that pre- and post-critical period loss of synchronous activity would differentially affect the perineuronal net of Y-type neurons in LGN and A17. METHODS: Seven adult cats, two normal, three convergent strabismic amblyopic, and two monocularly Y-blocked cats, were used in this study. The strabismic amblyopic cats had been made monocularly esotropic (by tenotomy) at 14 days of age. The Y-block was created acutely by a pressure cuff placed on the optic nerve behind the left eye in adult cats. The efficacy of both procedures was tested electrophysiologically. Frontal frozen sections were incubated with the Cat-301 antibody and the labeling visualized using a DAB kit. The sections were counterstained with cresyl violet. In each section, Cat-301-stained cells with well-defined nucleoli were counted under a 20x objective with a computer-based quantitative microscope image analysis system. RESULTS: The percentage of positively labeled cells was reduced in LGN laminae that received input from the deviated eye in amblyopic cats and from the pressure-blocked eye in Y-blocked cats compared with normal cats. Surprisingly, the non-blocked laminae of the Y-blocked cats also showed a significant reduction in positively labeled neurons when compared to normals or to strabismic cats. In the visual cortex of both hemispheres of strabismic and Y-blocked cats, the density of immunopositive neurons was significantly reduced compared with normal. The effect was most pronounced in layers IV-VI for Y-blocked cats and in layer IV for strabismic amblyopic cats. CONCLUSIONS: The results demonstrate that surface expression of aggrecan in adult cat LGN and A17 of adult cat is reduced both by chronic developmental loss of synchronous input from the two eyes and by acute changes in synchronous input in adulthood. Thus both pre- and post-critical plasticity in the expression of epitopes of aggrecan can be demonstrated. The uniform distribution of Cat-301 labeling tangentially within cortical layers of strabismic amblyopic cats indicates that the reduction in immunoreactivity observed with strabismus induced early in life is not simply eye-specific. Indeed, comparison of the immunopositivity of Y-blocked and strabismic animals, both in LGN and cortex, suggests that even after the critical period is ended, the physical removal of monocular Y-type afferent activity and weakening of binocular feedback connections between cortex and thalamus can alter the stability of the perineuronal nets surrounding the affected neurons.

Aggrecans↗
PubMed2004

Transiently higher release probability during critical period at thalamocortical synapses in the mouse barrel cortex: relevance to differential short-term plasticity of AMPA and NMDA EPSCs and possible involvement of silent synapses.

Thalamocortical connections undergo remarkable plasticity during the critical period and mounting evidence serves to demonstrate that the activation of silent synapses at postsynaptic sites is an important underlying mechanism in this process. However, relatively little is known about the nature of the presynaptic properties. In the present study, we examined the release probability (Pr) of thalamocortical synaptic terminals on a layer IV neuron in the developing mouse barrel cortex. Using the conventional paired-pulse ratio (PPR) method, both AMPA and NMDA receptor-mediated PPR were observed during development. We found that the NMDA PPR increased gradually (thus, a reduction in Pr) from postnatal day (P)4 to P22 but, unexpectedly, the AMPA PPR exhibited a simultaneous decrease. We then used an additional method for assessing release probability, the observation of a progressive block of NMDA receptor-mediated EPSCs using MK-801. With this method, we were able to identify two classes of terminals with high or low probabilities of release. Interestingly, the higher release showed a reduction in probability during the critical period, consistent with the NMDA PPR results. We confirmed that the discrepancy between the NMDA and the AMPA PPR results was due to the existence of silent, or NMDA-only, synapses, as suggested in previous literature. By analysing the correlation between the NMDA or AMPA PPR and the PPR discrepancy, we discuss the hypothesis that the terminals with transiently higher probability of release were found preferentially on silent synapses. Our results suggest that these presynaptic sites may also have an active role in plasticity by working concomitantly with postsynaptic sites during the critical period.

Age Factors↗
PubMed1994

The corticosteroidogenic response of brown and rainbow trout alevins and fry to environmental stress during a "critical period".

Postemergent salmonid fry experience a "critical period" in their development, during which there may be a high mortality rate, so determining the long-term success of the year class. The mechanism(s) underlying this phenomenon are not fully understood but physiological stress may be a contributory factor. This study sought to establish at what point in their development, posthatch, salmonids become stress responsive in terms of activation of the hypothalamic-pituitary-interrenal (HPI) axis. Immunoreactive corticosteroids were measured in tissue extracts of rainbow trout at intervals from 4 weeks prehatch to 27 weeks posthatch and in brown trout from 5 to 22 weeks posthatch. Corticosteroids were detectable throughout this period in both species. Simultaneous determination of whole-body immunoreactive corticosteroid levels (IRC) and plasma cortisol levels in fingerling trout validated the use of whole-body levels as an indicator of stress-induced elevation of corticosteroids. However, the dynamics of the circulating cortisol response to stress were not fully conveyed by whole-body measurements. From 5 weeks posthatch IRC increased significantly within 30-60 min following mechanical disturbance and confinement, suggesting a functional HPI axis to be present. An ectoparasite (Ichthyobodo sp.) infestation during this period caused a substantial increase in IRC levels in both species indicating that the HPI axis in these fish was sensitive to naturally occurring stressors. The response of fry to acute and chronic stress resembled that of adult fish in terms of duration. These data indicate that the early pre- and postemergent stages of salmonid fish are likely to be able to benefit from the adaptive advantage of HPI activation during episodes of acute stress but may also be susceptible to the deleterious consequences of prolonged activation of the HPI axis under conditions of chronic stress.

Adrenal Cortex Hormones↗
PubMed2003

Delayed and bilateral changes of GAP-43/B-50 phosphorylation after circling training during a critical period in rat striatum.

During the critical period of activity-dependent plasticity in rat striatum (30-37 days after birth) physiological circling behavior induces delayed modifications in GAP-43/B-50 phosphorylation by PKC. Postexercise, ipsi- and contralateral striatum to the circling direction show a similar temporal pattern of GAP-43/B-50 phosphorylation, with an initial decrease followed by a subsequent increase. However, there is a lag between initiation of the phosphorylation response in this asymmetrical task which does not occur when animals are subjected to exercise under conditions of symmetrical motor activity.

Animals↗
PubMed2005

Critical period plasticity in local cortical circuits.

Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.

Animals↗
PubMed2001

A new critical period for sensory map plasticity.

The development of neural circuits is influenced by sensory experience during restricted critical periods early in life. A novel critical period is demonstrated for plasticity of the whisker map in layer 2/3 of rat primary somatosensory cortex. Sensory experience during this period guides initial formation of whisker receptive fields.

Animals↗