Expression of Neurotrophic Factors in Human Dentin and Their Regulation of Trigeminal Neurite Outgrowth.

INTRODUCTION: Neurotrophic factors play a significant role in the innervation of the pulp-dentin complex during and after organogenesis. There have been numerous bioactive molecules identified in the dentin extracellular matrix; however, the expression of neurotrophic factors in the dentin matrix and their biological activity are largely unknown. The purpose of this study was to characterize the relative expression of neurotrophic factors in human dentin matrix proteins (DMPs) and their effect on neurite outgrowth of trigeminal (TG) neurons. METHODS: Dentin was powdered in liquid nitrogen from noncarious human third molar teeth. DMPs were solubilized through an EDTA extraction method, dialyzed, and lyophilized until use. The relative expression of nerve growth factor, brain-derived neurotrophic factor, glial cell-line derived neurotrophic factor, neurotrophin 3, and neurotrophin 4/5 was determined by the enzyme-linked immunosorbent assay. Rat TG neurons were cultured and exposed to different concentrations of DMPs (1-105 ng/mL) or vehicle, and a quantitative neurite outgrowth assay was performed. RESULTS: Human DMPs contained all of the tested neurotrophic factors, with glial cell-line derived neurotrophic factor and neurotrophin 4/5 found at the highest levels. DMPs were able to promote the neurite outgrowth of rat TG neurons at an optimum concentration of 10-102 ng/mL, whereas the effect was partially inhibited at higher concentrations (>103 ng/mL). CONCLUSIONS: The human dentin extracellular matrix is a rich reservoir for neurotrophic factors that are key components for neuronal homeostasis, differentiation, and regeneration. These data suggest that neurotrophins in DMPs could play an important role as signaling molecules for the innervation of the pulp-dentin complex during the processes of tooth formation, repair, and regeneration.

Nerve Growth and Interaction in Gelfoam® Histoculture: A Nervous System Organoid.

Nestin-expressing hair follicle-associated pluripotent (HAP) stem cells reside mainly in the bulge area (BA) of the hair follicle but also in the dermal papilla (DP). The BA appears to be origin of HAP stem cells. Long-term Gelfoam® histoculture was established of whiskers isolated from transgenic mice, in which there is nestin-driven green fluorescent protein (ND-GFP). HAP stem cells trafficked from the BA toward the DP area and extensively grew out onto Gelfoam® forming nerve-like structures. These fibers express the neuron marker ß-III tubulin-positive fibers and consisted of ND-GFP-expressing cells and extended up to 500 mm from the whisker nerve stump in Gelfoam® histoculture. The growing fibers had growth cones on their tips expressing F-actin indicating that the fibers were growing axons. HAP stem cell proliferation resulted in elongation of the follicle nerve and interaction with other nerves in 3D Gelfoam® histoculture, including the sciatic nerve, trigeminal nerve, and trigeminal nerve ganglion.

The significance of diffusion tensor magnetic resonance imaging for patients with nasopharyngeal carcinoma and trigeminal nerve invasion.

To investigate the significance of diffusion tensor imaging (DTI) for patients with nasopharyngeal carcinoma (NPC) and trigeminal nerve invasion.Fifty-two patients with NPC and unilateral infringement and 30 healthy controls were recruited for our study. Routine magnetic resonance imaging (MRI) and DTI were performed for all participants. Within-group and between-group comparisons of DTI metrics, including fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the third (V3) branch of the bilateral trigeminal nerves of all participants, were carried out.The FA and ADC values on the affected sides of patients revealed a significant decrease and increase, respectively, when compared with those on the unaffected sides of patients and the healthy controls (P = 0.000 for all), whereas there were no significant differences in DTI metrics between both sides of healthy controls or between the unaffected sides of patients and the healthy controls (P = 0.930, 0.580, 0.095, and 0.360, respectively). The decreasing FA rate on the affected sides of patients correlated negatively with the increasing ADC rate (r = -0.675, P = 0.000).DTI can quantitatively evaluate microstructural abnormalities of the V3 branch of the trigeminal nerve in patients with NPC, which is important for the early detection of trigeminal nerve invasion to achieve a precise T classification, assess prognosis, and guide treatment.

Sensory Activity-Dependent and Sensory Activity-Independent Properties of the Developing Rodent Trigeminal Principal Nucleus.

The whisker-sensory trigeminal central pathway of rodents is an established model for studies of activity-dependent neural plasticity. The first relay station of the pathway is the trigeminal principal nucleus (PrV), the ventral part of which receives sensory inputs mainly from the infraorbital branch of the maxillary trigeminal nerve (ION). Whisker-sensory afferents play an important role in the development of the morphological and physiological properties of PrV neurons. In neonates, deafferentation by ION transection leads to the disruption of whisker-related neural patterns (barrelettes) and cell death within a specific time window (critical period), as revealed by morphological studies. Whisker-sensory inputs control synaptic elimination, postsynaptic AMPA receptor trafficking, astrocyte-mediated synaptogenesis, and receptive-field characteristics of PrV cells, without a postnatal critical period. Sensory activity-dependent synaptic plasticity requires the activation of NMDA receptors and involves the participation of glia. However, the basic physiological properties of PrV neurons, such as cell type-specific ion channels, presynaptic terminal function, postsynaptic NMDA receptor subunit composition, and formation of the inhibitory circuitry, are independent of sensory inputs. Therefore, the first relay station of the whisker sensation is largely mature-like and functional at birth. Delineation of activity-dependent and activity-independent features of the postnatal PrV is important for understanding the development and functional characteristics of downstream trigeminal stations in the thalamus and neocortex. This mini review focuses on such features of the developing rodent PrV.

Developmental time course of peripheral cross-modal sensory interaction of the trigeminal and gustatory systems.

Few sensory modalities appear to engage in cross-modal interactions within the peripheral nervous system, making the integrated relationship between the peripheral gustatory and trigeminal systems an ideal model for investigating cross-sensory support. The present study examined taste system anatomy following unilateral transection of the trigeminal lingual nerve (LX) while leaving the gustatory chorda tympani intact. At 10, 25, or 65 days of age, rats underwent LX with outcomes assessed following various survival times. Fungiform papillae were classified by morphological feature using surface analysis. Taste bud volumes were calculated from histological sections of the anterior tongue. Differences in papillae morphology were evident by 2 days post-transection of P10 rats and by 8 days post in P25 rats. When transected at P65, animals never exhibited statistically significant morphological changes. After LX at P10, fewer taste buds were present on the transected side following 16 and 24 days survival time and remaining taste buds were smaller than on the intact side. In P25 and P65 animals, taste bud volumes were reduced on the denervated side by 8 and 16 days postsurgery, respectively. By 50 days post-transection, taste buds of P10 animals had not recovered in size; however, all observed changes in papillae morphology and taste buds subsided in P25 and P65 rats. Results indicate that LX impacts taste receptor cells and alters epithelial morphology of fungiform papillae, particularly during early development. These findings highlight dual roles for the lingual nerve in the maintenance of both gustatory and non-gustatory tissues on the anterior tongue.

Estimulación de nervios occipitales en el tratamiento de la migraña crónica refractaria / Occipital nerve stimulation for refractory chronic migraine

Introducción. La estimulación de nervios occipitales (ENO) es un tratamiento preventivo de la migraña crónica refractaria que está adquiriendo una importancia creciente en los últimos años. Objetivo. Evaluar el mecanismo de acción, estudios clínicos, técnica de implantación y criterios de inclusión de la ENO en el tratamiento preventivo de la migraña. Desarrollo. Se realiza una revisión no sistemática de la bibliografía sobre los aspectos anteriormente expuestos en la ENO como tratamiento para la migraña crónica. Esta patología afecta aproximadamente al 2% de la población y da lugar a una importante disminución de la calidad de vida e interferencia con las actividades laborales y sociales. La ENO es una terapia emergente y prometedora para el tratamiento de la migraña crónica que ha demostrado una disminución superior al 50% en el dolor en la mayoría de los estudios abiertos y ensayos clínicos publicados. Aunque el mecanismo de acción es desconocido, parece existir una neuromodulación de la información nociceptiva trigeminal en el núcleo caudal del trigémino explicada mediante la teoría de la puerta de entrada de Melzack y Wall. La ENO es un tratamiento seguro y bien tolerado, y los efectos secundarios son habitualmente locales, como desplazamiento de los electrodos o infecciones de la herida quirúrgica, que habitualmente no requieren su retirada. Conclusiones. La ENO es un tratamiento eficaz, bien tolerado y seguro en la prevención de la migraña crónica, y supone una opción útil para aquellos pacientes con migraña crónica refractaria a los tratamientos médicos convencionales (AU)

Introduction. Occipital nerve stimulation (ONS) is an emerging and promising preventive treatment for refractory chronic migraine. Aim. To evaluate the mechanisms of actions, clinical studies, implantation techniques and inclusion criteria of the ONS as a preventive treatment for migraine. Development. This work includes a non-systematic review of the literature on the above-mentioned aspects of ONS as a treatment for refractory chronic migraine. This disease affects approximately 2% of the population and results in a significant impairment in quality of life, economic burden and interference with labor and social activities. ONS is an emerging and promising therapy for the treatment of chronic migraine with greater than 50% pain reduction in most of open-label studies and published clinical trials. Although the mechanisms of action remain unknown, there seem to be a neuromodulation of the transmitted nociceptive trigeminal information in the trigeminal caudal nucleus, what could be explained by means of the Melzack and Wall pain gate theory. ONS is a safe and well tolerated treatment, and its most frequent side effects are usually local such as electrodes displacement or infections of the surgical incision. These complications do not usually require the electrodes withdrawal. Conclusions. ONS is an effective, well tolerated and safe treatment for the prevention of chronic migraine and could emerge as a useful option for those patients with medically refractory chronic migraine (AU)

Corneal epithelial and neuronal interactions: role in wound healing.

Impaired corneal innervation and sensitivity are the main causes of corneal neurotrophic keratopathy which simultaneously also leads to poor epithelial wound healing. Restoration of the diminished communication between the corneal epithelium and trigeminal nerve is indispensable for the proper functioning of the epithelium. The present study aims to investigate corneal epithelial and trigeminal neuron interactions to shed light on corneal wound healing during neurotrophic keratopathy. Mouse trigeminal neurons and corneal epithelial cells were cultured according to standard methods. To study the effect of corneal epithelial cells on trigeminal neurons as well as the effect of trigeminal neurons on corneal epithelial cells during wound healing, conditioned media from the cultures of pure trigeminal neurons (CNM) and corneal epithelial cells (CEM) were collected freshly and applied on the other cell type. Neurite outgrowth assay and RT-PCR analysis using primers specific for substance P (SP), Map1a, Map1b were performed on trigeminal neurons in the presence of CEM. We observed an increase in the neurite outgrowth in the presence of CEM and also in co-culture with corneal epithelial cells. Increase in the expression of SP mRNA and a decrease in the expression of Map1b mRNA was observed in the presence of CEM. We also observed the presence of epithelial-to-mesenchymal transition (EMT)-like phenomenon during wound healing using a scratch assay in primary corneal epithelial cultures. This system was further employed to study the effect of CNM on corneal epithelial cells in the context of wound healing to find the effect of trigeminal neurons on epithelial cells. RT-PCR analysis of Pax6 expression in corneal epithelial cell cultures with scratch served as a positive control. Further, we also show the expression of bone morphogenetic protein 7 (BMP7) mRNA in corneal epithelial cells which is decreased gradually along with Pax6 mRNA when cultured together in the presence of CNM. The expression and down regulation of BMP7 in the presence of CNM was further confirmed at the protein level by western blotting. From this study it seems that the epithelial and neuronal interactions in the cornea may contribute to the corneal innervation as well as recovery of corneal epithelial cells during injury. Appraising the differences in the expression of various signalling molecules during EMT of epithelial cells in the presence of SP and BMP7 gives an insight into the detailed dissection of the involved signalling pathways to develop future therapeutics.

New transgenic reporters identify somatosensory neuron subtypes in larval zebrafish.

To analyze somatosensory neuron diversity in larval zebrafish, we identified several enhancers from the zebrafish and pufferfish genomes and used them to create five new reporter transgenes. Sequential deletions of three of these enhancers identified small sequence elements sufficient to drive expression in zebrafish trigeminal and Rohon-Beard (RB) neurons. One of these reporters, using the Fru.p2x3-2 enhancer, highlighted a somatosensory neuron subtype that expressed both the p2rx3a and pkcα genes. Comparison with a previously described trpA1b reporter revealed that it highlighted the same neurons as the Fru.p2x3-2 reporter. To determine whether neurons of this subtype possess characteristic peripheral branching morphologies or central axon projection patterns, we analyzed the morphology of single neurons. Surprisingly, although these analyses revealed diversity in peripheral axon branching and central axon projection, PKCα/p2rx3a/trpA1b-expressing RB cells did not possess obvious characteristic morphological features, suggesting that even within this molecularly defined subtype, individual neurons may possess distinct properties. The new transgenes created in this study will be powerful tools for further characterizing the molecular, morphological, and developmental diversity of larval somatosensory neurons.

Developmental changes in human dural innervation.

INTRODUCTION: There is limited published work on the abundant innervation of the human dura mater, its role and responses to injury in humans. The dura not only provides mechanical support for the brain but may also have other functions, including control of the outflow of venous blood from the brain via the dural sinuses. The trigeminal nerve supplies sensory fibres to the dura as well as the leptomeninges, intracranial blood vessels, face, nose and mouth. Its relatively large size in embryonic life suggests an importance in development; the earliest fetal reflexes, mediated by the trigeminal, are seen by 8 weeks. Trigeminal functions vital to the fetus include the coordination of sucking and swallowing and the protective oxygen-conserving reflexes. Like other parts of the nervous system, the trigeminal undergoes pruning and remodelling throughout development. METHODS: We have investigated changes in the innervation of the human dura with age in 27 individuals aged between 31 weeks of gestation and 60 years of postnatal life. Using immunocytochemistry with antibodies to neurofilament, we have found significant changes in the density of dural innervation with age RESULTS: The density of innervation increased between 31 and 40 weeks of gestation, peaking at term and decreasing in the subsequent 3 months, remaining low until the sixth decade. CONCLUSIONS: Our observations are consistent with animal studies but are, to our knowledge, the first to show age-related changes in the density of innervation in the human dura. They provide new insights into the functions of the human dura during development.

Robo2 determines subtype-specific axonal projections of trigeminal sensory neurons.

How neurons connect to form functional circuits is central to the understanding of the development and function of the nervous system. In the somatosensory system, perception of sensory stimuli to the head requires specific connections between trigeminal sensory neurons and their many target areas in the central nervous system. Different trigeminal subtypes have specialized functions and downstream circuits, but it has remained unclear how subtype-specific axonal projection patterns are formed. Using zebrafish as a model system, we followed the development of two trigeminal sensory neuron subtypes: one that expresses trpa1b, a nociceptive channel important for sensing environmental chemicals; and a distinct subtype labeled by an islet1 reporter (Isl1SS). We found that Trpa1b and Isl1SS neurons have overall similar axon trajectories but different branching morphologies and distributions of presynaptic sites. Compared with Trpa1b neurons, Isl1SS neurons display reduced branch growth and synaptogenesis at the hindbrain-spinal cord junction. The subtype-specific morphogenesis of Isl1SS neurons depends on the guidance receptor Robo2. robo2 is preferentially expressed in the Isl1SS subset and inhibits branch growth and synaptogenesis. In the absence of Robo2, Isl1SS afferents acquire many of the characteristics of Trpa1b afferents. These results reveal that subtype-specific activity of Robo2 regulates subcircuit morphogenesis in the trigeminal sensory system.

BAPTI and BAPTISM birthdating of neurons in zebrafish.

This protocol describes how the photoconvertible protein Kaede can be used to determine the birthdates of neurons in live zebrafish. The methods used are birthdating analysis by photoconverted fluorescent protein tracing in vivo (BAPTI) and BAPTI combined with subpopulation markers (BAPTISM). Because Kaede can be converted from green to red fluorescence at any developmental time point, it serves as a temporal landmark for cell birth. When it is used in combination with subpopulation markers, the eventual fate of a cell can be correlated with its birthdate. We describe how we used this method to study the development of trigeminal sensory neurons and discuss how the technique can be extended to the study of other organs.

[Participation of serotonin in the mechanisms of the formation of trigeminal motor nucleus].

The formation of trigeminal motor nucleus (TMN) was studied in the early postnatal period in 21 female Wistar rats which received the serotonin biosynthesis inhibitor para-chloro-phenylalanine at prenatal Day 16 (the period of serotoninergic system formation). It was shown that the serotonin deficit during the prenatal period in rats resulted in the changes of TMN structural organization. In the early postnatal period, the delay of neuropil development, the reduction of cell body size with the partial loss of Nissl substance in some of the neurons, the presence of degenerating neurons with the signs of hyperchromatosis in all the parts of the nucleus, especially in TMN ventromedial part, were detected. At later stages, the destruction of motoneurons became slower, though some of them had morphological abnormalities. With the increase of the postnatal age (by Day 20) the number of motor neurons decreased, apparently, as a result of the gradual intensification of cell death. Simultaneously with the motor neuron degeneration in TMN parts studied, the astrocytic gliosis was observed.

Progressive postnatal motoneuron loss in mice lacking GDF-15.

Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of the TGF-beta superfamily with prominent neurotrophic effects on midbrain dopaminergic neurons. We show here that GDF-15-deficient mice exhibit progressive postnatal losses of spinal, facial, and trigeminal motoneurons. This deficit reaches a approximately 20% maximum at 6 months and is accompanied by losses of motor axons and significant impairment of rotarod skills. Similarly, sensory neurons in dorsal root ganglia (L4, L5) are reduced by 20%, whereas sympathetic neurons are not affected. GDF-15 is expressed and secreted by Schwann cells, retrogradely transported along adult sciatic nerve axons, and promotes survival of axotomized facial neurons as well as cultured motor, sensory, and sympathetic neurons. Despite striking similarities in the GDF-15 and CNTF knock-out phenotypes, expression levels of CNTF and other neurotrophic factors in the sciatic nerve were unaltered suggesting that GDF-15 is a genuine novel trophic factor for motor and sensory neurons.

Morphometric analysis of the skull of the Sahel goat breed: basic and clinical anatomy.

The work reports morphometric analysis of the skulls of the Sahel breed of goat. The calculated metric data (mean +/- SD) included the condylobasal length, 16.94 +/- 1.39 cm, while the orbital circumference was 11.30 +/- 0.48 cm. The foramen magnum height and width were 1.82 +/- 0.11 cm and 1.85 +/- 0.15 cm respectively while the foramen magnum index was 89.81 +/- 8.71. Animals above one year of age had significantly higher values for orbital length including horizontal and vertical diameters, overall skull length, basal length, and neurocranium height than animals aged one year and below. The cornual process length, maximum orbital circumference and horizontal diameter obtained in this study were higher than those reported for other Nigerian goat breeds in the literature. The data for the distances from the facial tuberosity to the infraorbital canal, from the mental foramen to the lateral extent of the alveolar root of the lower incisor, as well as from the mandibular foramen to the base of the mandible and that from the mental foramen to the caudal border of the mandible, which are important clinically in the estimation of craniofacial measurements that will aid regional anaesthesia, were however similar to those reported earlier for the Red Sokoto and West African Dwarf breeds implying that a uniform craniometric estimation for associated regional nerve blocks can be attempted for these goat breeds.

mGluR5 regulates glutamate-dependent development of the mouse somatosensory cortex.

We have previously reported that mGluR5 signaling via PLC-beta1 regulates the development of whisker patterns within S1 (barrel) cortex of mice (Hannan et al., 2001). However, whether these defects arise from the loss of postsynaptic mGluR5 signaling, and whether the level of mGluR5 is important for barrel formation, was not examined. Furthermore, whether mGluR5 regulates other developmental processes that occur before or after barrel development is not known. We now show that mGluR5 is present postsynaptically at thalamocortical synapses during barrel formation. In addition, Mglur5(+/-) mice exhibit normal TCA patch formation but reduced cellular segregation in layer 4, indicating a dose-dependent role for mGluR5 in the regulation of pattern formation. Furthermore Mglur5(-/-) and Mglur5(+/-) mice display normal cortical arealization, layer formation, and size of PMBSF indicating the defects within S1 do not result from general abnormalities of cortical mapping during earlier stages of development. At P21 layer 4 neurons from Mglur5(-/-) and Mglur5(+/-) mice show a significant reduction in spine density but normal dendritic complexity compared with Mglur5(+/+) mice indicating a role in synaptogenesis during cortical development. Finally, mGluR5 regulates pattern formation throughout the trigeminal system of mice as the representation of the AS whiskers in the PrV, VpM, and S1 cortex was disrupted in Mglur5(-/-) mice. Together these data indicate a key role for mGluR5 at both early and late stages of neuronal development in the trigeminal system of mice.

[Expression and activity of Cdk5/p39 during rats Vc development].

PURPOSE: To evaluate the different expression of Cdk5 two activators, p35 and p39 throughout rats Vc development. METHODS: The changes of Cdk5 activity, expression of Cdk5 and p39 in the development in spinal trigeminal subnucleus caudalis(Vc) were studied by Western blotting, immunoprecipitation and kinase assay. Statistical analysis was performed using SPSS11.0 software package. RESULTS: Western blot showed that p39 expression was low at newborn, and highest at the 2-3 week-old rat Vc. In the adult rat Vc, expression declined to the same level as in newborn rat Vc. In contrast, the expression of Cdk5 was constant throughout the development rat Vc. Cdk5 activity in the newborn rat Vc(115.5 Kcpm),which was about 6 times higher than that in normal adult rat Vc(19.0 Kcpm). There was significant difference between each group(P<0.01). CONCLUSIONS: Expression of p35 and p39 is differentially distributed throughout rat Vc. Cdk5/p35 and Cdk5/p39 may play different roles in distinct brain regions during different states of the rat Vc development.

Multiple tooth-losses during development suppress age-dependent emergence of oscillatory neural activities in the oral somatosensory cortex.

Tooth and tooth-related organs play important roles in not only mastication, but also sensory perception in the oral region. In general, sensory neural inputs during the developmental period are required for the maturation of functions in the sensory cortex. However, whether maturations of oral somatosensory cortex (OSC) require certain levels of sensory input from oral regions has been unclear. The present study investigated the influence of multiple tooth-losses during the developmental period on age-dependent emergence of rhythmic activities of population neurons in the OSC. Low-frequency electrical stimulation was delivered to layer IV and field potentials were recorded from layer II/III in the OSC of rat brain slices. In control rats, N-methyl-d-aspartate (NMDA) receptor-dependent oscillation at 8-10 Hz appeared during postnatal weeks 2-3. In rats with extraction of multiple teeth at 17-18 days old, oscillation did not appear even at maturity, whereas in rats with multiple teeth extracted at 37-38 days old, oscillation appearances were maintained in maturity. Thus, emergence of oscillation in the OSC was suppressed by multiple tooth-losses during postnatal 2-3 weeks. These results suggest that sufficient neural inputs from the teeth and tooth-related organs during developmental periods are essential for maturation of neural functions in the OSC.

The influence of pregnancy and gender on perivascular innervation of rat posterior cerebral arteries.

The authors investigated the influence of pregnancy and gender on the density of trigeminal and sympathetic perivascular nerves in posterior cerebral arteries (PCA) and the reactivity to norepinephrine and calcitonin gene-related peptide (CGRP). PCAs were isolated from nonpregnant, late-pregnant, postpartum, and male rats, mounted and pressurized on an arteriograph chamber to obtain concentration-response curves to norepinephrine and CGRP. Arteries were immunostained for CGRP-, tyrosine hydroxylase-, and protein gene product 9.5 (PGP 9.5)-containing perivascular nerves, and nerve density was determined morphologically. Pregnancy had a trophic effect on trigeminal perivascular innervation (P < .01 vs male); however, this was not accompanied by a change in reactivity to CGRP. Sympathetic and PGP 9.5 nerve densities were not altered by pregnancy or gender, and there were no differences in reactivity to norepinephrine. Together, these results suggest that the increase in trigeminal innervation during pregnancy is more related to nociception than in controlling resting cerebral blood flow.

Developmental exposure to ethanol or nicotine inhibits the hypercapnic ventilatory response in tadpoles.

Tadpoles, Lithobates (formerly Rana) catesbeiana, were held for 8-12 weeks in pond water that was either teratogen free or contained 0.15% ethanol or 30 microg/L nicotine. The ventilatory and neuroventilatory consequences of these developmental exposures were assessed. Developmental exposure to ethanol or nicotine blocked the hypercapnia-induced increase in surfacing frequency typically exhibited by tadpoles, as well as the hypercapnia-induced increase in putative lung ventilation exhibited by isolated tadpole brainstems. It was specifically the hypercapnic ventilatory response, previously characterized as an increase in lung activity, that was affected by developmental exposure to these teratogens. Developmental exposure to ethanol or nicotine did not affect the frequency of surfacing or putative lung breaths exhibited by the intact tadpoles or their isolated brainstems when not subjected to a hypercapnic challenge.

Development of thalamocortical response transformations in the rat whisker-barrel system.

Extracellular single-unit recordings were used to characterize responses of thalamic barreloid and cortical barrel neurons to controlled whisker deflections in 2, 3-, and 4-wk-old and adult rats in vivo under fentanyl analgesia. Results indicate that response properties of thalamic and cortical neurons diverge during development. Responses to deflection onsets and offsets among thalamic neurons mature in parallel, whereas among cortical neurons responses to deflection offsets become disproportionately smaller with age. Thalamic neuron receptive fields become more multiwhisker, whereas those of cortical neurons become more single-whisker. Thalamic neurons develop a higher degree of angular selectivity, whereas that of cortical neurons remains constant. In the temporal domain, response latencies decrease both in thalamic and cortical neurons, but the maturation time-course differs between the two populations. Response latencies of thalamic cells decrease primarily between 2 and 3 wk of life, whereas response latencies of cortical neurons decrease in two distinct steps--the first between 2 and 3 wk of life and the second between the fourth postnatal week and adulthood. Although the first step likely reflects similar subcortical changes, the second phase likely corresponds to developmental myelination of thalamocortical fibers. Divergent development of thalamic and cortical response properties indicates that thalamocortical circuits in the whisker-to-barrel pathway undergo protracted maturation after 2 wk of life and provides a potential substrate for experience-dependent plasticity during this time.