Hodgkin lymphoma incidence in California Hispanics: influence of nativity and tumor Epstein-Barr virus.

PURPOSE: For classical Hodgkin lymphoma (HL), migrant studies could elucidate contributions of environmental factors (including Epstein-Barr virus (EBV)) to the lower rates in non-whites. Given the well-described etiologic complexity of HL, this research requires a large, immigrant population, such as California Hispanics. METHODS: With 1988-2004 California Cancer Registry data (2,595 Hispanic, 8,637 white HL cases) and tumor cell EBV status on a subset (218 Hispanics, 656 whites), we calculated ethnicity- and nativity-specific HL incidence rates simultaneously by age, sex, and histologic subtype, and tumor cell EBV prevalence. RESULTS: Compared with white rates, Hispanic HL rates were lower overall (70 %) and for nodular sclerosis HL, particularly among young adults (60-65 % for females). However, they were higher among children (200 %) and older adults, and for mixed cellularity HL. Compared with rates in foreign-born Hispanics, rates in US-born Hispanics were higher among young adults (>threefold in females), lower for children and adults over age 70, and consistently intermediate compared with rates in whites. EBV tumor prevalence was 67, 32, and 23 % among foreign-born Hispanics, US-born Hispanics, and whites, respectively, although with variation by age, sex, and histology. CONCLUSIONS: Findings strongly implicate environmental influences, such as nativity-related sociodemographic differences, on HL occurrence. In addition, lower young adult rates and higher EBV prevalence in US-born Hispanics than in whites raise questions about the duration/extent of environmental change for affecting HL rates and also point to ethnic differences in genetic susceptibility. Lesser variation in mixed cellularity HL rates and greater variation in rates for females across groups suggest less modifiable factors interacting with environmental influences.

Risk of lymphoma subtypes after solid organ transplantation in the United States.

BACKGROUND: Solid organ transplant recipients have high risk of lymphomas, including non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). A gap in our understanding of post-transplant lymphomas involves the spectrum and associated risks of their many histologic subtypes. METHODS: We linked nationwide data on solid organ transplants from the US Scientific Registry of Transplant Recipients (1987-2008) to 14 state and regional cancer registries, yielding 791 281 person-years of follow-up for 19 distinct NHL subtypes and HL. We calculated standardised incidence ratios (SIRs) and used Poisson regression to compare SIRs by recipient age, transplanted organ, and time since transplantation. RESULTS: The risk varied widely across subtypes, with strong elevations (SIRs 10-100) for hepatosplenic T-cell lymphoma, Burkitt's lymphoma, NK/T-cell lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma (both systemic and primary cutaneous forms). Moderate elevations (SIRs 2-4) were observed for HL and lymphoplasmacytic, peripheral T-cell, and marginal zone lymphomas, but SIRs for indolent lymphoma subtypes were not elevated. Generally, SIRs were highest for younger recipients (<20 years) and those receiving organs other than kidneys. CONCLUSION: Transplant recipients experience markedly elevated risk of a distinct spectrum of lymphoma subtypes. These findings support the aetiologic relevance of immunosuppression for certain subtypes and underscore the importance of detailed haematopathologic workup for transplant recipients with suspected lymphoma.

Obesity, waist size and prevalence of current asthma in the California Teachers Study cohort.

BACKGROUND: Obesity is a risk factor for asthma, particularly in women, but few cohort studies have evaluated abdominal obesity which reflects metabolic differences in visceral fat known to influence systemic inflammation. A study was undertaken to examine the relationship between the prevalence of asthma and measures of abdominal obesity and adult weight gain in addition to body mass index (BMI) in a large cohort of female teachers. METHODS: Prevalence odds ratios (ORs) for current asthma were calculated using multivariable linear modelling, adjusting for age, smoking and race/ethnicity. RESULTS: Of the 88 304 women in the analyses, 13% (n = 11,500) were obese (BMI > or = 30 kg/m(2)) at baseline; 1334 were extremely obese (BMI > or = 40 kg/m(2)). Compared with those of normal weight, the adjusted OR for adult-onset asthma increased from 1.40 (95% confidence interval (CI) 1.31 to 1.49) for overweight women to 3.30 (95% CI 2.85 to 3.82) for extremely obese women. Large waist circumference (>88 cm) was associated with increased asthma prevalence, even among women with a normal BMI (OR 1.37, 95% CI 1.18 to 1.59). Among obese women the OR for asthma was greater in those who were also abdominally obese than in women whose waist was < or = 88 cm (2.36 vs 1.57). Obese and overweight women were at greater risk of severe asthma episodes, measured by urgent medical visits and hospital admissions. CONCLUSIONS: This study confirms the association between excess weight and asthma severity and prevalence, and showed that a large waist was associated with increased asthma prevalence even among women considered to have normal body weight.

The formation of a cortical somatotopic map.

The primary somatosensory cortex of small rodents is an isomorphic representation of the body surface. Similar representations are characteristic of the subcortical pathways, leading from the periphery to the cortex, and these representations develop in a sequence that begins at the periphery, and that ends in the cortex. Furthermore, central representations at all levels of the neural axis are altered by perinatal perturbations of the peripheral surface. This has led to the hypothesis that the periphery plays an instructional role in the formation of central neuronal structures. The morphology of this discrete organization has been examined thoroughly during the development of the thalamocortical projections. The mechanism(s) that underlies the formation of these representations remains unclear although some recent evidence suggests the involvement of activity-dependent processes that are modulated by 5-HT.

Is cytoplasmic Ca2+ in lymphocytes elevated in cystic fibrosis?

An increased cytoplasmic Ca2+ concentration ( [Ca2+]i) has been implicated in the pathogenesis of cystic fibrosis. We compared the [Ca2+]i levels of normal and cystic fibrosis peripheral blood lymphocytes and Epstein-Barr virus-transformed lymphoblasts using quin 2, an internally trapped indicator. The [Ca2+]i levels of normal and cystic fibrosis cells were not significantly different. The ionophore-releasable intracellular Ca2+ stores were also comparable in both types of individual.

Activation of Na+/H+ exchange in lymphocytes by osmotically induced volume changes and by cytoplasmic acidification.

After swelling in hypotonic solutions, peripheral blood mononuclear cells (PBM) shrink toward their original volumes. Upon restoration of isotonicity, the cells initially shrink but then regain near-normal size again. This regulatory volume increase (RVI) is abolished by removal of Na+o or Cl-o or by addition of amiloride. RVI is unaffected by removal of K+o or by ouabain and is only partially inhibited by 1 mM furosemide. As a result of increased influx, the cells gain both Na+ and K+ during reswelling. In contrast, only Na+ content increases in the presence of ouabain. Amiloride largely eliminates the changes in the content of both cations. Using diS-C3-(5), no significant membrane potential changes were detected during RVI, which suggests that the fluxes are electroneutral. The cytoplasmic pH of volume-static cells was measured with 5,6-dicarboxyfluorescein. After acid loading, the addition of extracellular Na+ induced an amiloride-inhibitable alkalinization, which is consistent with Na+/H+ exchange. Cytoplasmic pH was not affected by cell shrinkage itself, but an internal alkalinization, which was also amiloride sensitive and Na+ dependent, developed during reswelling. In isotonic lightly buffered solutions without HCO-3, an amiloride-sensitive acidification of the medium was measurable when Na+ was added to shrunken PBM. K+ was unable to mimic this effect. The observations are compatible with the model proposed by Cala (J. Gen. Physiol. 1980. 76:683-708), whereby an electroneutral Na+o/H+i exchange is activated by osmotic shrinking. Cellular volume gain occurs as Cl-o simultaneously exchanges for either HCO-3i or OH-i. Na+i is secondarily replaced by K+ through the pump, but this step is not essential for RVI.

Volume-induced increase of anion permeability in human lymphocytes.

Peripheral blood mononuclear cells (PBM) readjust their volumes after swelling in hypotonic media. This regulatory volume decrease (RVD) is associated with a loss of cellular K+ and is thought to be promoted by an increased permeability to this ion. In contrast, no change in volume was observed when K+ permeability of PBM in isotonic media was increased to comparable or higher levels using valinomycin. Moreover, valinomycin-induced 86Rb+ loss in K+-free medium was considerably slower than in K+-rich medium. These results suggest that anion conductance limits net salt loss in isotonic media. Direct measurements of relative conductance confirmed that in volume-static cells, anion conductance is lower than that of K+. In volume-regulating cells depolarization occurred presumably as a result of increased anion conductance. Accordingly, the efflux of 36Cl from PBM was markedly increased by hypotonic stress. Since both membrane potential and intracellular 36Cl concentration are reduced in hypotonically swollen cells, the increased efflux is probably due to a change in Cl- permeability. Anions and cations seem to move independently through the volume-induced pathways: the initial rate of 86Rb uptake in swollen cells was not affected by replacement of external Cl- by SO=4; conversely, 36Cl fluxes were unaffected by substitution of K+ by Na+. The data indicate that anion conductance is rate-determining in salt and water loss from PBM. An increase in anion conductance is suggested to be the critical step of RVD of human PBM.

Normal development and effects of neonatal infraorbital nerve damage upon the innervation of the trigeminal brainstem complex by primary afferent fibers containing calcitonin gene-related peptide.

Immunocytochemistry was used to study the normal development and response to infraorbital nerve (ION) damage of the innervation of the trigeminal (V) brainstem complex by axons recognized by an antibody directed against calcitonin gene-related peptide (CGRP). CGRP-like immunoreactivity (CGRPLI) was present in axons that occupied the outer V spinal tract (TrV) at all levels of the V brainstem complex. Almost no fibers terminated within V nucleus principalis (PrV), but there was dense CGRPLI in the supratrigeminal nucleus. There was also very little CGRPLI within rostral V subnucleus oralis (SpO). However, in the caudal one-half of the nucleus, a dense elongated patch of immunoreactivity was consistently present just medial to TrV. Only occasional CGRP-positive axons could be seen within V subnucleus interpolaris (SpI), but the paratrigeminal nucleus contained dense immunoreactivity. Trigeminal subnucleus caudalis (SpC) also contained CGRPLI that was very dense in lamina I and the outer portion of lamina II. Scattered terminals were also present in layers III and IV and dense terminal clusters were in lamina V. CGRP-immunoreactive neurons were present in the V ganglion by embryonic (E-) day 16 and immunoreactive axons could be seen in the V brainstem complex on E-17. At birth, CGRP-positive axons in the V brainstem complex had achieved a distribution very similar to that in adult rats. The major difference between the patterns of labelling in neonates and adults was the presence of relatively large numbers of CGRP-positive fibers in ventral PrV and SpO of the former animals. The disappearance of these fibers was completed by the middle of the third postnatal week. Transection of the ION on the day of birth had little effect upon CGRP in SpO, SpI, and SpC, but it did result in an increase in CGRP-positive fibers in PrV ipsilateral to the damaged nerve. When considered together with previous findings, these results suggest that CGRP-positive axons express this peptide well after they have entered the V brainstem complex and that the central terminal field of these fibers is not substantially altered by a manipulation which results in the death of nearly 60% of all V primary afferent neurons.

Effects of cortical and thalamic lesions upon primary afferent terminations, distributions of projection neurons, and the cytochrome oxidase pattern in the trigeminal brainstem complex.

Early postnatal lesions of the primary somatosensory cortex alter the vibrissa-related cytochrome oxidase (CO) pattern in nucleus principalis (PrV) of the rat's trigeminal (V) brainstem complex (Erzurumlu and Ebner, '88: Dev. Brain Res. 44:302-308). At present, the reason for this change is not clear. It may be that the corticotrigeminal projection is necessary for the maintenance of vibrissa-related patterns in PrV. However, it is also possible that the loss of the normal pattern of CO activity reflects a change in the organization of brainstem cells resulting from transneuronal retrograde degeneration. In order to address this question, we made lesions of either the primary somatosensory cortex (S-I) or ventrobasal thalamus (VB) in newborn rats and directly assayed distribution of V primary afferents by transganglionic transport of horseradish peroxidase and V-thalamic neurons by retrograde transport of either fluorogold or true blue. Neonatal cortical and thalamic lesions produced no qualitative change in the distribution of primary afferent terminals in either PrV or V subnucleus interpolaris (SpI) beyond that which could be attributed to shrinkage of the brainstem resulting from retrograde degeneration. Most importantly, the "patchy" pattern of terminations observed in normal rats remained apparent in the brain-damaged animals. The normal distribution of V-thalamic neurons in PrV was disrupted by both cortical and thalamic lesions. These cells are normally patterned in a way that matches the distribution of primary afferent terminals and thus that of the mystacial vibrissae. This was not the case in the neonatally brain-damaged rats. Taken together, these results are consistent with the conclusion that neonatal cortical and thalamic lesions disrupt the normal CO pattern in PrV primarily because of their effects upon the patterning of brainstem cells. The present findings demonstrate further that clustering of primary afferents does not require a normal complement of postsynaptic neurons.

Increased serotoninergic innervation of the hamster's superior colliculus alters retinotectal projections.

Anterograde tracing with horseradish peroxidase (HRP) was used to compare the organization of retinotectal projections in normal adult hamsters and in animals that sustained subcutaneous injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on the day of birth. Neonatal injection of this neurotoxin decreases the density of the serotoninergic (5-HT) innervation of the cerebral and cerebellar cortices, but increases the density of these fibers in the brainstem including the superior colliculus (SC). Analysis of tissue from the retinorecipient laminae of the SC by high-pressure liquid chromatography indicated that these lesions increased the amount of 5-HT in the adult SC by 47%. The increased serotoninergic innervation of SC was associated with a marked change in the distribution of the uncrossed retinotectal projection. In normal adult hamsters, fibers from the ipsilateral eye form dense clusters in the lowermost stratum griseum superficiale (SGS) and stratum opticum (SO). A small number of uncrossed fibers are also visible in the more caudal portions of these layers. In the animals that sustained neonatal 5,7-DHT injections, uncrossed retinotectal fibers formed a nearly continuous band in rostral SO and lower SGS, and numerous labeled fibers were present in the caudal SC, primarily in the SO. Neonatal treatment with 5,7-DHT also produced alterations in the crossed retinotectal pathway and in the crossed and uncrossed retinogeniculate projections. These results indicate that the 5-HT input to the developing brainstem may strongly influence the development of retinofugal projections.

Immunochemical heterogeneity in the tecto-LP pathway of the rat.

The projection from the rat's superior colliculus (SC) to the lateral posterior nucleus of the thalamus (LP) has previously been described as arising from a morphologically homogeneous population of neurons in the stratum opticum (SO). The present study combined immunocytochemistry with retrograde tracing and lesion techniques to determine whether or not the SC-->LP projection arose from neurons that were also neurochemically homogeneous. The combination of retrograde tracing and immunocytochemistry with an antibody directed against calbindin-D 28K (CBD) showed that 64.4% of the neurons that project from SC to LP contain this calcium-binding protein. Retrograde tracing and immunocytochemistry for adenosine deaminase (ADA) showed that a smaller number of tecto-LP cells (15.7%) were immunoreactive (IR) for this enzyme. Moreover, nearly all (93.0%) of the ADA-IR tecto-LP cells also contained CBD-IR. Adenosine deaminase-IR axons in LP were restricted to the dorsomedial portion of the nucleus and their density was substantially reduced after ablation of the ipsilateral superficial SC laminae. The lateral posterior nucleus contained numerous CBD-IR cells and fibers throughout its extent and it was thus difficult to determine the extent to which the extra-perikaryal CBD-IR in this nucleus was dependent upon the tecto-LP pathway. Nevertheless, destruction of the ipsilateral SC did reduce the density of CBD-IR in LP. These results suggest that the SC-->LP projection in rat arises from at least four neurochemically distinct cell groups: 1) those that contain CBD, 2) those that contain both CBD and ADA, 3) a very small population that contains only ADA, and 4) a group that is not recognized by either of these markers. Our results further suggest that ADA containing fibers may have a more restricted terminal distribution in LP than axons that contain only CBD.

Patterning of the neocortical projections from the raphe nuclei in perinatal rats: investigation of potential organizational mechanisms.

Serotoninergic (5-HT) fibers in the cerebral cortex of perinatal rats have a pattern that coincides with the boundaries of primary sensory areas and within the primary somatosensory cortex form the rattunculus. This patterned immunoreactivity (IR) appears about 60 hours after birth and disappears between postnatal days (P-) 12 and 15. Three experiments were carried out to evaluate mechanisms that might underlie the precise patterning of the 5-HT-IR. Retrograde labelling with fluorescent tracers in perinatal rats revealed only a coarse rostrocaudal topography in the raphe-cortical projection and the existence of raphe cells projecting to multiple cortical locations. Thus, a precise point-to-point, raphe-cortical projection does not underlie the patterned cortical 5-HT-IR. Ablation of the thalamus prior to the age at which patterned 5-HT-IR could be seen in the developing cortex caused a complete loss of patterned immunoreactivity. This suggests that 5-HT fibers may require the presence of thalamocortical axons to achieve the pattern observed in normal animals. Serotoninergic raphe neurons transplanted to the cortices of newborn rats exhibited extensive axonal outgrowth, but did not form a somatotopic pattern. This result also suggests that specific spatiotemporal interactions between growing 5-HT and thalamocortical axons may be necessary for the somatotopic patterning of the former fibers.

Effect of activity blockade on changes in vibrissae-related patterns in the rat's primary somatosensory cortex induced by serotonin depletion.

Depletion of cortical serotonin (5-HT) during development results in a decrease in the size of the patches of thalamocortical afferents representing the mystacial vibrissae in lamina IV of the primary somatosensory cortex (SI). We previously suggested that this change may be due to a reduction in 5-HT-induced suppression of thalamocortical activity in these animals. The present experiments directly tested the role that modulation of activity may play in the morphologic changes observed after reducing cortical 5-HT concentrations. Serotonin was depleted from the cortex by systemic administration of 5,7-dihydroxytryptamine (5,7-DHT, 100 mg/kg) on the day of birth in animals that also had either tetrodotoxin (TTX)-impregnated or control implants placed unilaterally over the developing SI on this day. Other rat pups were treated with TTX-impregnated or control implants alone. Administration of 5,7-DHT reduced cortical serotonin levels and this effect was not significantly modified by the presence of either control or TTX-impregnated cortical implants. Administration of 5,7-DHT reduced the cross-sectional area of the cortical patches, demonstrated by acetylcholinesterase, corresponding to the vibrissae by 19.9% (P < 0.05). A similar reduction was observed in the animals treated with both 5,7-DHT and TTX-impregnated implants. Treatment with TTX-impregnated implants alone resulted in a 3.1% increase in patch size (P > 0.05). None of the treatments significantly altered the overall area of the part of SI devoted to the representation of the long mystacial vibrissae. These results suggest that the effects of 5-HT depletion on the size of the cortical patches representing the long vibrissae are independent of activity that can be blocked by administration of TTX.

Patterning of local intracortical projections within the vibrissae representation of rat primary somatosensory cortex.

Anterograde and retrograde tracing with biotinylated dextran amine and Phaseolus vulgaris leukoagglutinin was used to assess projection patterns within the vibrissae representation of the rat's primary somatosensory cortex (S-I). Large and small injections of either tracer into the center of the vibrissae representation yielded dense anterograde and retrograde labelling throughout much of the tangential extent of the vibrissae representation within S-I. In all layers, the pattern and extent of retrograde and anterograde label was in rough congruence. The organization of this labelling varied across cortical layers. In layers II and III, labelled fibers extended away from injection sites in all directions and yielded a uniform pattern, which decreased in density with increasing distance from the tracer injection. There was a tendency for labelling to be more extensive along the representation of the row of vibrissae follicles that included the injection site than across rows. There was also a tendency for anterograde labelling to be more extensive in the direction of the representation of follicles more rostral on the face than that injected. In lamina IV, both labelled fibers and cells were restricted for the most part to the septa regions between the barrels. However, a small number of retrogradely labelled neurons were also located in the barrels (approximately one-ninth of the number found in the septa). The pattern observed in laminae II-III was repeated in layers V and VI. In these laminae, there was no evidence of a pattern of intracortical connections related to the vibrissae representation in overlying lamina IV.

Development and plasticity of local intracortical projections within the vibrissae representation of the rat primary somatosensory cortex.

Labelling with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Di-A) was used to assess the development of projections within the primary somatosensory cortex (SI) of rats aged between postnatal day 2 and 8 (P-2 and P-8). 1,1'-Dioctadecyl-3,3,3,"3'-tetramethylindocarbocyanine perchlorate (Di-I) was used in these same animals to label thalamocortical afferents. Particular attention was paid to the emergence of lamina IV intracortical projections that form a pattern complementary to vibrissae-related thalamocortical afferents. A vibrissae-related pattern of Di-A-labelled cells and fibers that was restricted largely to the septa regions was not apparent in rats killed on P-2, but it was visible in animals killed on P-4 and later ages. Tracing with biotinylated dextran amine (BDA) was used to assess intra-SI projections of adult rats that sustained transection of the infraorbital nerve (ION) on P-0 or P-7 or implantation of a tetrodotoxin (TTX)-impregnated polymer chip over the cortex on P-0. Rats that sustained ION transection on P-7 or that had TTX implants demonstrated normal patterns of projections within SI. The patterns of labelling in the supra- and infragranular layers of the cortices of the rats that sustained ION transection on P-0 were generally similar to those in the other groups evaluated. However, in lamina IV, there was no organization that could be related to the distribution of the vibrissae. These results indicate that the vibrissae-related pattern of intracortical projections within SI develops shortly after birth and that two manipulations that alter cortical activity, but not the patterning of thalamocortical afferents (application of TTX and transection of the ION after thalamocortical afferent patterns are established), have no significant effect on it. However, a manipulation that alters thalamocortical development (transection of the ION on P-0) profoundly affects the patterning of intracortical connections.

Long-term effects of neonatal axoplasmic transport attenuation on the organization of the rat's trigeminal system.

The current study examined the long-term effects of infraorbital nerve (ION) axoplasmic transport attenuation with vinblastine on the organization of trigeminal (V) primary afferents and central vibrissae-related patterns. Retrograde tracing and single unit recording were used to evaluate the innervation of vibrissae follicles in adult (P > 60) rats that sustained application of vinblastine to the ION at birth. Single units recorded from vinblastine-treated animals yielded responses to deflection of a single vibrissa, and a significantly (P < 0.001) higher percentage of these cells (85.7%) showed rapidly adapting responses compared with normal rats (42.2%). Retrograde tracing revealed a qualitatively and normal distribution of V ganglion cells innervating A-row and E-row vibrissae follicles in vinblastine-treated rats. Transganglionic tracing with horseradish peroxidase (HRP) demonstrated a qualitatively and quantitatively normal somatotopic organization of vibrissae follicle input to V nucleus principalis (PrV) and V subnucleus interpolaris (SpI) in the vinblastine-treated animals. Despite the nearly normal mapping of V ganglion cell axons onto the vibrissae follicles and brainstem, staining for either cytochrome oxidase (CO) or parvalbumin failed to reveal vibrissae-related patterns in PrV, SpI, or the magnocellular portion of V subnucleus caudalis in these animals. Labelling of thalamocortical afferents with HRP and staining for CO also failed to reveal a cortical vibrissae-related pattern in the vinblastine-treated rats. The present results indicate that although transient attenuation of axoplasmic transport with vinblastine has limited effects on the peripheral and central projections of surviving V primary afferents, it permanently disrupts the normal development and maintenance of central vibrissae-related patterns.

Thalamic processing of vibrissal information in the rat. I. Afferent input to the medial ventral posterior and posterior nuclei.

Retrograde tracing with true blue (TB) and diamidino yellow (DY) and anterograde tracing with either wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L) were employed to investigate the projections from trigeminal nucleus principalis (PrV) and trigeminal subnucleus interpolaris (SpI) to their targets in the medial ventral posterior (VPM) and posterior (POm) nuclei of the thalamus. Many more cells in both PrV and SpI were labeled by tracer injections into VPM than into POm. Only a very small number of double-labeled neurons were observed in either PrV or SpI. However, a significantly higher percentage of SpI cells projected to POm or to both POm and VPM than was the case for PrV. Anterograde tracing with WGA-HRP showed that the projections from both PrV and SpI to VPM were much denser than those from the same nuclei to POm. Small injections of PHA-L into either PrV or SpI produced a focus of fairly dense labeling in VPM and much more diffuse terminal labeling in POm. These anatomical data provide evidence for two separate trigeminothalamic pathways, one originating from PrV and the second originating from SpI. Both of these pathways converge and diverge at the thalamic level. That is, information from the PrV pathway and from the SpI pathway are both provided to VPM in a morphologically restricted fashion and to POm in a morphologically widespread fashion.

Parvalbumin and calbindin immunocytochemistry reveal functionally distinct cell groups and vibrissa-related patterns in the trigeminal brainstem complex of the adult rat.

Immunocytochemistry for calbindin (CA) and parvalbumin (PA) was combined with retrograde tracing from the thalamus, superior colliculus (SC), and cerebellum to define the ascending projections of neurons in the rat's trigeminal (V) brainstem complex that express immunoreactivity for these calcium binding proteins. Many PA-immunoreactive neurons were observed in trigeminal nucleus principalis (PrV). Many of these cells projected to thalamus and a few sent axons to SC. In ventral PrV, PA-immunoreactive neurons were arranged in a vibrissa-related pattern. A very small number of large CA-immunoreactive neurons were observed in dorsomedial PrV. None of these cells were labeled by our tracer deposits. Small neurons in V subnucleus oralis (SpO) were also immunoreactive for PA, but none were retrogradely labeled. A small percentage of the large neurons in SpO were CA-immunoreactive; many of these were retrogradely labeled by tracer injections in the thalamus and/or SC. In V subnucleus interpolaris (SpI), many small to medium sized cells were PA-positive and they were arrayed in a vibrissae-like pattern. None of these neurons were retrogradely labeled from any of the above-listed targets, but many were retrogradely labeled by tracer injections into ipsilateral PrV. SpI also contained many large CA-immunoreactive cells. Many of these projected to the thalamus and/or SC and some were also retrogradely labeled by tracer injections into ipsilateral PrV. In V subnucleus caudalis (SpC), very dark PA-immunoreactive neurons were located in the inner part of lamina II and less often in laminae I. Lightly labeled cells were located in the magnocellular laminae and formed vibrissa-related aggregates. None of these neurons were retrogradely labeled by our tracer injections. CA-immunoreactive cells were located throughout the depth of lamina II in SpC and smaller numbers were also visible in lamina I and layers III-V. A small percentage of the CA-positive cells in lamina I and in the magnocellular layers were retrogradely labeled from the thalamus. These data indicate that PA and CA antisera identify two cell populations in whisker-related regions of the V brainstem complex and that PA cells are somatotopically patterned in PrV, SpI, and SpC. These markers also distinguish two cell groups in superficial laminae of the medullary dorsal horn.

Sensitive period for lesion-induced reorganization of intracortical projections within the vibrissae representation of rat's primary somatosensory cortex.

Previous experiments from this laboratory demonstrated that intracortical connections in lamina IV of the rat primary somatosensory cortex (SI) are most dense outside the patches of cytochrome oxidase (CO) staining that correspond to the mystacial vibrissae. This pattern of intracortical connections becomes apparent on postnatal day 4 (P-4), at least 2 days after the appearance of the vibrissae-related pattern of thalamocortical afferents. Transection of the infraorbital nerve (ION) on the day of birth (P-0) disrupts both the CO and intracortical projection patterns. This series of experiments was undertaken to determine whether the patterning of either thalamocortical afferents or intracortical projections defines the end of the period over which peripheral damage can alter intracortical projections in lamina IV of SI. The infraorbital nerve (ION) was transected in different cohorts of rats on P-1 through P-5, and animals were allowed to survive > or =45 days, at which time biotinylated dextran amine (BDA) injections were made into the SI. After 7 days, animals were killed, and alternate cortical sections were processed for the demonstration of BDA or CO. Transection of the ION on P-1 or P-2 altered the patterning of both CO and intracortical connections in the SI. In contrast, cutting the ION on P-3 left the pattern of CO densities in the SI intact, but significantly altered the patterning of intracortical connections. Transection of the nerve on P-5 resulted in qualitatively and quantitatively normal patterns of both CO densities and BDA-labelled intracortical projections. These results indicate that the establishment of a stable barrel pattern in layer IV of the SI is not sufficient for normal adult patterning of intracortical projections in this lamina. However, once the mature pattern of intracortical projections in layer IV is established, ION lesions can no longer alter it.