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PubMed2005

Variation in the cortical area map of C57BL/6J and DBA/2J inbred mice predicts strain identity.

BACKGROUND: Recent discoveries suggest that arealization of the mammalian cortical sheet develops in a manner consonant with principles established for embryonic patterning of the body. Signaling centers release morphogens that determine regional growth and tissue identity by regulating regional expression of transcription factors. Research on mouse cortex has identified several candidate morphogens that affect anteroposterior or mediolateral cortical regionalization as well as mitogenesis. Inbred strains of laboratory mice can be exploited to study cortical area map formation if there are significant phenotypic differences with which to correlate gene polymorphism or expression data. Here we describe differences in the cortical area map of two commonly used inbred strains of laboratory mice, C57BL/6J and DBA/2J. Complete cortical hemispheres from adult mice were dissected and stained for the cytochrome oxidase enzyme in order to measure histochemically defined cortical areas. RESULTS: C57BL/6J has the larger neocortex, relatively larger primary visual cortex (V1), but relatively smaller posterior medial barrel subfield of the primary somatosensory cortex (PMBSF). The sample of C57BL/6J and DBA/2J mice can be discriminated with 90% accuracy on the basis of these three size dimensions. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, suggesting that inbred strains harbor enough phenotypic variation to encourage a forward genetic approach to understanding cortical development, complementing other approaches.

Animals↗
PubMed1992

The development of neuropeptide Y-immunoreactive neurons in a model of pure cortical culture.

The development of neuropeptide Y-immunoreactive neurons in the rat brain cerebral cortex was studied in a model of a pure cortical culture. In this model, development of neurons devoid of any afferents from other brain structures could be observed. Since mutual interactions between neuropeptide Y and catecholamines have been postulated, such a pure cortical culture offers a possibility of studying the development of neuropeptide Y neurons devoid of any brainstem monoaminergic afferents. A tissue dissected from 16-day-old rat fetuses and cultivated in a dissociated culture for 14 days was examined immunohistochemically for the presence of neuropeptide Y-immunoreactive neurons. Three main types of neuropeptide Y-immunoreactive neurons were found: unipolar, bipolar and multipolar. Cell processes and terminal varicose fibres were also observed. The results obtained indicate that neuropeptide Y-immunoreactive neurons and fibres may develop in a pure culture of the rat cerebral cortex without the influence of any other structures.

Animals↗
PubMed1991

Development of the cerebellar cortical efferent projection: an in-vitro anterograde tracing study in rat brain slices.

This study reports the results of an anterograde HRP analysis of the development of cerebellar cortical efferents studied in-vitro with cerebellum-brainstem slices from embryonic (E-18) through newborn rats. From E-18, Purkinje cells in the medial region of the cerebellum are seen to project to the medial cerebellar and vestibular nuclei, their appropriate targets in the adult animal. Thus, the cortical efferent system is forming during late embryogenesis and may establish synaptic contacts with target cells as early as E-20.

Animals↗
PubMed1984

Early development of changes in cortical representation of C3 vibrissa following neonatal denervation of surrounding vibrissa receptors: a 2-deoxyglucose study in the rat.

The development of changes in cortical representation of a C3 mystacial vibrissa in the rat was studied with [14C]2-deoxyglucose (2-DG) autoradiography after neonatal unilateral ablation of all but the C3 whisker follicle. The 2-DG-labeled column, which was produced by stroking the spared C3 vibrissa, was enlarged (35%) at postnatal day (p.d.) 5 and reached 140% by p.d. 12, as compared to the control C3 vibrissa column in the opposite hemisphere. The diameter of the C3 barrel itself on the involved side was about 40% larger than that of the control side at all ages. Based upon the above postoperative survival times, at least two stages in the altered development of the spared C3 vibrissa column are suggested.

Afferent Pathways↗
PubMed2000

Neonatal serotonin depletion affects developing and mature mouse cortical neurons.

The early expression of neurotransmitters and receptors in the developing brain has brought attention to their potential contribution in modulating neuronal developmental processes. Monoamines are among the first neurotransmitter systems to develop during embryogenesis. Depletion of neocortical serotonin or catecholamine afferents with selective neurotoxins resulted in a permanent alteration of the dendritic arborization of calretinin-containing interneurons, and a transient delay of parvalbumin and calbindin expression in a number of cortical neurones during the second postnatal week. The expression pattern of other developmentally regulated proteins, such as two subunits of the GABA(A) receptor, was not altered. Depletion of serotonin, and in part catecholamines, appeared to perturb several developmental processes of the cerebral cortex which would interfere with both its maturation and adult circuitry.

5,7-Dihydroxytryptamine↗
PubMed1991

The effect of alpha-adrenergic receptor blockers prazosin and yohimbine on cerebral metabolism and biogenic amine content of traumatized brain.

Widespread decrease in local cerebral glucose utilization (LCGU) previously shown to occur 3 days after a local freezing lesion was interpreted as reflecting a depression of functional activity in the affected areas. In parallel experiments, cortical norepinephrine (NE) content of traumatized brain was found to be decreased. The effects of prazosin (PZ), an alpha 1-adrenergic receptor blocker, and yohimbine (YOH), an alpha 2-blocker, on glucose use and biogenic amine content of lesioned rat brain were studied to determine if the changes in the noradrenergic system associated with injury are of functional importance, to identify the receptors that may be involved in mediating the action of NE in injured brain, and to look for evidence of interaction between the noradrenergic and the serotonergic systems in traumatized brain. PZ (1 mg/kg) given 30 min before the lesion ameliorated the subsequent metabolic cortical depression seen in untreated animals. PZ given for 3 days starting before the lesion (3 mg/kg/day) was also effective in normalizing LCGU in areas where it was depressed by lesioning, despite the fact that this regimen induced significant global decrease in LCGU in normal animals. Once cortical metabolic depression had developed 3 days after the lesion, it could not be modified by PZ. YOH was less effective than PZ and was so only when given for 3 days (22.5 mg/kg/day in three divided doses). PZ (3 mg/kg/day in three divided doses) slightly but significantly decreased the accumulation of the serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid in the traumatized hemisphere. These results provide evidence that blockage of alpha 1-adrenergic receptors prevents the development of cortical dysfunction associated with brain trauma. This implies that the noradrenergic system plays a role in the functional consequences of injury and that this effect is, at least in part, mediated by alpha 1-adrenergic receptors. Furthermore, alpha 1-adrenergic receptor blockage appears to modulate cortical turnover of 5-HT, previously also implicated in functional consequences of brain injury. The data are compatible with inhibitory effects of NE in the cortex and suggest a potential of alpha 1-adrenergic blockage in development of novel therapeutic approaches to brain injury.

Animals↗
PubMed1992

Development of subpopulations of GABAergic neurons in cat visual cortical areas.

The development of GABAergic interneurons in feline striate area and extrastriate areas was tracked by single and double labeling immunohistochemistry using antibodies to GABA and to molecular markers which identify subpopulations of GABAergic neurons in adult mammalian neocortex; i.e., neuropeptide Y, somatostatin, and the calcium-binding proteins parvalbumin and calbindin. The density of GABA-ir neurons was relatively constant during development and among visual areas. By contrast, most of the GABA-subpopulations increased in the cortex of visual areas during postnatal development, and thus the proportion of GABA-ir neurons which also expressed another molecular marker increased during development. By the end of the first postnatal month, the neurotransmitter phenotypes of the neocortical GABAergic neurons are mature.

Aging↗
PubMed1970

Early experience effects upon cortical dendrites: a proposed model for development.

We studied the effects of environmental stimulation on the development of rat cortical pyramidal cell synaptic loci (dendritic spines) and the number of such cells staining by the rapid Golgi technique. Stimulation three to five times a day from the day of birth increased the number of spines per micrometer in 8-day-old animals and increased the number of neurons stanining at 8 to 16 days of age. This effect of afferent input upon development of the dendritic spine may represent the neuroanatomical basis for the influence of early experience on subsequent behavior. The number of neurons staining by the rapid Golgi technique appears to be related to those that are functionally involved at the time of tissue preparation.

Animals↗
PubMed1990

Somatostatin gene expression in the developing monkey frontal and cerebellar cortices.

Somatostatin (SRIF) mRNA was determined in the developing monkey frontal and cerebellar cortices by the dot blot and the northern blot analyses at embryonic day 120 (E120), embryonic day 140 (E140), newborn stage (Nb), postnatal day 60 (P60) and adult stage (Ad.) At E120, at which time the migration of the cortical neurons had already been completed, SRIF mRNA was detectable with 50% of the maximal value at E140 in the cerebral frontal cortex (von Bonin and Bailey's area FD). After E140, the level of mRNA gradually declined to the adult level by P60 with 25% of the maximal value. In the cerebellum, SRIF mRNA was highly expressed at E120. The level decreased to 18% of the maximum at E140. Between the newborn and adult stages, there existed no positive signal of the mRNA. In contrast, both fetal and adult liver tissues contained no amounts of SRIF mRNA. We discussed the physiological meanings of the enhanced SRIF gene expression in the developing monkey cerebral and cerebellar cortices.

Aging↗
PubMed2006

Development of cataract and associated risk factors: the Visual Impairment Project.

OBJECTIVE: To evaluate risk factors for the development of cataract in Australian residents. METHODS: A total of 3721 participants from 9 randomly selected urban districts within Victoria were recruited and invited to attend comprehensive standardized interviews and ophthalmic examinations at baseline and then 5-year follow-up. Lens opacities were graded clinically and on photographs according to the Wilmer cataract grading system. The development of cortical, nuclear, and posterior subcapsular cataract were assessed separately for associated risk factors. Risk exposure at baseline was used as the predictor for cataract development, which included various sociodemographic, dietary, familial, medical, and ocular characteristics of the participants. Risk factor analyses were performed by univariate and multivariate logistic regression. RESULTS: Increased age was a risk factor for development of all types of cataract with an increasing risk trend throughout life for nuclear cataract. Female sex, a laborer's occupation, and myopia were independent risk factors for development of cortical cataract. For development of nuclear cataract, the independent risk factors were having a birthplace outside Australia and New Zealand, current cigarette smoking, and having a history of arthritis. Diabetes mellitus and having taken calcium channel blockers for longer than 5 years were independent risk factors for posterior subcapsular cataract. CONCLUSIONS: The trend of increasing incidence of cataract with increased age is a major public health concern with an aging population in Australia and the world. Among the risk factors identified, cigarette smoking is a factor that is readily modifiable and preventable. The other risk factors identified require further support or clarification of underlying mechanisms to find modifiable features.

Adult↗
PubMed1974

The effect of visual experience on the development of stimulus specificity by kitten cortical neurones.

1. 284 single cortical neurones were studied in area seventeen of twenty-five normal kittens and of fifteen kittens, binocularly deprived, whose first visual experience had been delayed until the experiment by bilateral lid-suture. Both normal and binocularly deprived kittens ranged in age from 1 to 6 weeks.2. The optimal, binocularly presented, visual stimulus and receptive fields were determined for each neurone by varying target configuration, speed and direction of movement and the prism-induced alignment of both eyes. Repetitive, controlled stimulation in eighty-four cases allowed quantitative estimates to be made of the response selectivity for the target configuration (spot vs. line), the direction of target motion and the prism-induced disparity between the retinal images of the binocular target.3. Before the fourth post-natal week neurones from both normal and binocularly deprived cortex showed similar properties: selectivity for direction of target motion was present in both preparations but both lacked binocular specificity and dependence on target configuration.4. After the fourth week, normal kittens had increasing numbers of neurones with selective responses which were dependent upon target configuration and the degree of binocular misalignment. The proportion of selective neurones approached the adult value after the fifth week.5. The cortex of binocularly deprived kittens failed to show an increase of selectivity with age, and of 150 neurones, sixty-two were visually unresponsive, two showed selectivity which was dependent upon target configuration and none showed selectivity for prism-induced retinal disparity.6. The data are not consistent with the hypothesis that the highly specific response properties of visual cortical neurones can develop without appropriate visual experience. Innate mechanisms appear to be sufficient for the development of the excitatory connexions producing motion sensitivity and receptive field location on both retinas, but patterned visual experience is necessary for the ;fine-tuning' which vetoes responses to stimuli with non-optimal configuration or binocular disparity.

Action Potentials↗
PubMed1989

The roles of glucocorticosteroid and of fibrinolytic activity in the development of bilateral renal cortical necrosis in cycloheximide-treated mice challenged with a submicrogram dose of endotoxin.

Mice given cycloheximide and 0.2 microgram of endotoxin simultaneously developed ischaemic bilateral renal cortical necrosis as part of a fatal syndrome. Endotoxin given 2 h after cycloheximide, although fatal, failed to produce renal cortical necrosis. Investigation suggested that, following endotoxin challenge in cycloheximide-treated mice, the occurrence or non-occurrence of bilateral renal cortical necrosis was determined by the concentration of circulating glucocorticoids at the time of endotoxin challenge. Thus, below a certain, as yet undefined, glucocorticoid concentration, endotoxin does not cause renal cortical necrosis in cycloheximide-treated mice. Inhibition of the fibrinolytic system by epsilonaminocaproic acid (EACA) indicated that protection against renal cortical necrosis was directly mediated by increased fibrinolytic activity. Since this increased activity occurred during a period of profound cycloheximide-mediated inhibition of protein synthesis, it was postulated that pre-existing plasminogen activator was released from inhibition, and that this release could only occur when the glucocorticoid concentration fell below a certain critical value.

Aminocaproic Acid↗
PubMed1986

Sex dependent behavioral response to frontal cortical suction lesions in the rat.

Previous reports indicate that male rats given right (but not left) frontal cortical suction lesions develop hyperactivity accompanied by cortical norepinephrine depletions. In this study, female rats given such lesions to either hemisphere developed bilateral cortical norepinephrine depletions but no hyperactivity. Right lesion male rats developed both catecholamine depletions and hyperactivity. Thus, the lateralized hyperactivity response to these cortical lesions is sex-dependent and may involve sex differences in subcortical neural pathways.

Animals↗
PubMed1989

Quadrature and the development of orientation selective cortical cells by Hebb rules.

We describe a new theoretical scenario for the development of orientation selective cells in a self-organizing feedforward network with modifiable synapses. A suitable choice of Hebb rule leads to a system that develops symmetric and antisymmetric response fields (quadrature pairs) at the same time as directional selectivity occurs using inhibition between neighboring cells. Quadrature phase relationships between the response properties of adjacent cortical cells is suggestive of several highly efficient information processing strategies.

Animals↗
PubMed2003

Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions.

Neurotrophins strongly affect visual system development and plasticity. However, the mode of delivery and targets of neurotrophin action are still under debate. For instance, cortical NT-4/5 (neurotrophin 4/5; Ntf4/5) was shown to rescue lateral geniculate nucleus (LGN) neurons from monocular deprivation-induced atrophy suggesting a retrograde action on thalamic afferents. It is still unclear whether LGN neurons respond to NT-4/5 and other neurotrophins during development in animals with normal vision. We now show that infusions of NT-4/5 and NGF (nerve growth factor) into visual cortex at the onset and the peak of the critical period accelerated LGN neuron growth. BDNF (brain-derived neurotrophic factor) was ineffective. The effects of neurotrophin on LGN development were clearly dissociated from the effects at cortical level because soma growth of cortical layer IV and VI neurons was strongly promoted by BDNF. NT-4/5 was only effective at the onset, but no longer at the peak of the critical period suggesting a switch in neurotrophin dependency for these cortical cell classes. To dissociate retrograde and anterograde effects of the TrkB ligands, we analyzed the stratum griseum superficiale (SGS) of the superior colliculus, a target of visual cortical efferents. Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth. Strikingly, the TrkB-expressing excitatory tectothalamic calbindin neurons in the SGS did not respond. This demonstrated for the first time a selective cell type-specific anterograde action of NT-4/5 and suggested for the LGN that anterograde as well as retrograde effects contribute to soma size regulation. Strikingly, cortical infusion of the cytokine LIF, which affects development of visual cortex neurochemical architecture, transiently inhibited growth of neurons in LGN, cortical layer IV and VI and SGS. In summary, the study presents three important results. First, central neurons regulate soma size development in an age-and ligand-specific fashion. Second, NT-4/5 and NGF accelerate LGN development in rats with normal vision while LIF delays growth. Third, anterogradely transported NT-4/5 effectively promotes neuronal maturation. These differential actions on subcortical neurons may contribute to the different effects of neurotrophins on visual system development and plasticity.

Afferent Pathways↗
PubMed2006

Development of visually evoked cortical activity in infant macaque monkeys studied longitudinally with fMRI.

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development.

Animals↗
PubMedDate not supplied

Effects of neonatal toluene exposure on the development of evoked and spontaneous cortical activity in the rat.

The effects of neonatal toluene exposure on the development of cortical evoked responses to sciatic nerve and light stimulation, as well as the spontaneous Electrocorticogram (ECoG) of frontal and occipital regions, were studied in rats at different developmental ages. The major findings following the solvent exposure were a significant prolongation in the mean peak latencies of both primary and secondary cortical evoked responses the effects being more severe in the sensorimotor area than in the visual cortical region. Additionally the experimental animals did not show significant differences in the average frequencies histograms of the ECoG in both neocortical areas when compared with control littermates. The data suggest that early toluene exposure was primarily affecting those brain structures underlying locomotor abilities than those related with the functionality of the CNS visual centers.

Aging↗
PubMed2001

Suppression of cortical NMDA receptor function prevents development of orientation selectivity in the primary visual cortex.

Selectivity to visual stimulus orientation is a basic cortical functional property believed to be crucial for normal vision. Maturation of this neuronal property requires neural activity. Still, it is unclear what might be the molecular basis for such activity-dependent processes and whether activity has an instructive or permissive role in development of orientation selectivity. There is strong evidence that the NMDA subtype of the glutamate receptor regulates activity-dependent mechanisms of ocular dominance plasticity during cortical development. For this reason, we have hypothesized that the NMDA receptor participates in activity-dependent mechanisms that sculpt orientation selectivity of cortical neurons. We used chronic in vivo infusion of antisense oligodeoxynucleotides (ODNs) to suppress NMDA receptor function in primary visual cortex during the period when orientation selectivity develops in ferrets. Chronic suppression of NMDA receptor function prevented the development of orientation and stimulus size selectivity in most cortical cells tested. In contrast, treatment with control sense or missense ODNs did not affect development of orientation selectivity, indicating specificity of effects. Importantly, antisense ODN treatment did not impair visually driven activity, which is required for development to occur. Moreover, orientation selectivity of cortical cells was not disrupted by antisense ODN treatment in mature animals, indicating developmental relevance of the effects. In conclusion, our findings document for the first time that cortical NMDA receptors are essential for the maturation of orientation selectivity. This result supports the notion that activity has an instructive role in sculpting the connections that underlie orientation selectivity in visual cortex.

Aging↗