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PubMed1991

mRNA transcripts initiating within the human immunoglobulin mu heavy chain enhancer region contain a non-translatable exon and are extremely heterogeneous at the 5' end.

Transcription events are thought to precede gene rearrangement in the immunoglobulin (Ig) loci and may be the mechanism by which the various gene regions are made accessible for recombination. If this is the case, identification and characterization of transcripts from the Ig loci should permit a better understanding of the gene rearrangement process. We have isolated a 2.3 kb cDNA clone from the human pre-B cell line Nalm-1 that contains enhancer-specific sequences from the Ig heavy (H) chain gene locus. The 2.3 kb transcript initiated within the enhancer region and showed extreme 5' heterogeneity, with more than 50 initiation sites mapping near the Ig-specific octamer ATTTGCGT. Sequencing of the cDNA clone demonstrated that 644 nucleotides from the Ig enhancer region were incorporated as a leader exon spliced to the mu constant (Cmu) region. This leader exon contained many translation termination codons and may function to inhibit the translation of sterile Cmu polypeptides. Using an enhancer-derived probe, we detected two low-abundancy mRNA transcripts with sizes of 2.3 and 12 kb. Northern blot analysis suggested that the 12 kb transcript was the unspliced precursor mRNA of a VDJ rearrangement. The potential role of these enhancer-containing transcripts in the opening of the IgH chain gene for rearrangement and for class switching is discussed.

Amino Acid Sequence↗
PubMed1997

Hyaluronidase enhancement of TNF-mediated cell death is reversed by TGF-beta 1.

Both hyaluronidase and transforming growth factor (TGF)-beta 1 play a significant role in the development of prostate cancer. In this study, the regulation of tumor necrosis factor (TNF)-mediated cell death by hyaluronidase and TGF-beta 1 was investigated. Preexposure of L929 fibroblasts, prostate LNCaP cells, and epithelial Mv 1 Lu cells to hyaluronidase for a minimum of 12 h resulted in significant enhancement of cell death by TNF. Phosphorylation of p42 and p44 mitogen-activated-protein (MAP) kinases was found by stimulation of L929 cells with hyaluronidase for 30 min, indicating that the Raf/MAP kinase-extracellular signal-regulating protein kinase (MEK)/ MAP kinase pathway was activated. However, blocking the activation of upstream MAP kinase kinase (MEK 1 and 2 kinase) by PD-98059 failed to inhibit the hyaluronidase-enhanced TNF killing of cells, suggesting that hyaluronidase-mediated degradation of extracellular matrix and membrane components may elicit multiple signaling pathways. As a potent stimulator of extracellular matrix protein synthesis, TGF-beta 1 blocked the hyaluronidase-enhanced death of L929 and LNCaP cells mediated by TNF. TGF-beta 1 activated protein-tyrosine kinases in L929 cells, in which the tyrosine kinase inhibitors lavendustin A and tyrphostin blocked the activation as well as the TGF-beta 1 inhibition of hyaluronidase effects. Functional antagonism was also observed between hyaluronidase and TGF-beta 1 in cell growth regulation. For example, TGF-beta 1-mediated suppression of epithelial Mv 1 Lu cell growth was abolished by hyaluronidase. Overall, it is demonstrated in this study that hyaluronidase reciprocally antagonized TGF-beta 1 in the modulation of cell proliferation and TNF-mediated death.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Mapping and cloning recombinant breakpoints demarcating the hybrid sterility 6-specific sperm tail assembly defect.

Variants of the mouse t complex known as t haplotypes (t) express factors that perturb sperm differentiation, resulting in the non-Mendelian transmission of t from +/t heterozygous males and the sterility of t/t homozygous males. Previous studies of mice carrying heterospecific combinations of the t complex have revealed a 1-cM candidate locus, Hst6, for the distal-most of these factors, Tcd/Tcs2. Males heterozygous for the M. spretus allele of Hst6 and a t haplotype (Hst6(s)/t) are sterile, expressing an abnormality in sperm flagellar curvature ("curlicue") indistinguishable from one exhibited by sperm from t/t homozygotes. Hst6(s)/Hst6(s) males are also sterile; however, sperm produced by these males are completely immotile owing to the absence of assembled flagella. Recent studies have shown that the complete presentation of "curlicue" derives from expression of at least two factors within the locus, Curlicue a (Ccua) proximally and Curlicue b (Ccub) distally, with a factor affecting sperm-oolemma penetration, Stop1p, mapping between them. In the present report, we have examined expression of the Hst6-specific flagellar assembly phenotype in sperm from mice homozygous for M. spretus-M. m. domesticus recombinant Chr 17 homologs whose breakpoints map within the Hst6 locus. SSLP analysis of these homologs has demonstrated that the flagellar assembly defect maps to less than 0.2 cM between D17Mit61 and D17Mit135, coincident with Ccua. SSR content analysis of 23 BACs mapping to four contigs within the Hst6 locus has resulted in isolation of proximal and distal recombinant breakpoints circumscribing the flagellar assembly phenotype/Ccua factor. In addition, we have provided increased high-resolution mapping of the Stop1p and Ccub factors. These new data enhance our ability to isolate and characterize candidates for Tcd/Tcs2.

Animals↗
PubMed2001

Insulin signal transduction in rat small intestine: role of MAP kinases in expression of mucosal hydrolases.

The postreceptor events regulating the signal of insulin downstream in rat intestinal cells have not yet been analyzed. Our objectives were to identify the nature of receptor substrates and phosphorylated proteins involved in the signaling of insulin and to investigate the mechanism(s) by which insulin enhances intestinal hydrolases. In response to insulin, the following proteins were rapidly phosphorylated on tyrosine residues: 1) insulin receptor substrates-1 (IRS-1), -2, and -4; 2) phospholipase C-isoenzyme-gamma; 3) the Ras-GTPase-activating protein (GAP) associated with Rho GAP and p62(Src); 4) the insulin receptor beta-subunit; 5) the p85 subunits of phosphatidylinositol 3-kinase (PI 3-kinase); 6) the Src homology 2 alpha-collagen protein; 7) protein kinase B; 8) mitogen-activated protein (MAP) kinase-1 and -2; and 9) growth receptor-bound protein-2. Compared with controls, insulin enhanced the intestinal activity of MAP kinase-2 and protein kinase B by two- and fivefold, respectively, but did not enhance p70/S6 ribosomal kinase. Administration of an antireceptor antibody or MAP-kinase inhibitor PD-98059 but not a PI 3-kinase inhibitor (wortmannin) to sucklings inhibited the effects of insulin on mucosal mass and enzyme expression. We conclude that normal rat enterocytes express all of the receptor substrates and mediators involved in different insulin signaling pathways and that receptor binding initiates a signal enhancing brush-border membrane hydrolase, which appears to be regulated by the cascade of MAP kinases but not by PI 3-kinase.

Animals↗
PubMed2005

A model for research on the blood-brain barrier disruption induced by unsaturated fatty acid emulsion.

PURPOSE: The authors investigated whether fatty acid emulsion affects the blood-brain barrier (BBB), whether disrupted BBB is reversible, and whether the fatty acid emulsion technique may be a model for BBB research. MATERIALS AND METHODS: The fat emulsion was made with 0.05 mL of oleic acid or linoleic acid and 20 mL of normal saline. The internal carotid artery in 14 cats was infused with oleic acid emulsion (group 1) and with linoleic acid emulsion in 12 cats (group 2). Gd-enhanced T1-weighted (Gd-T1WI), diffusion-weighted (DWI), and additional apparent diffusion coefficient (ADC) map magnetic resonance imaging (MRI) was obtained at 1 hour, 1 and 4 days, and 1 week after infusion. MRI findings were evaluated qualitatively. Quantitatively, the signal intensity ratio (SIR) of the lesion to the contralateral hemisphere was measured on Gd-T1WIs. The SIRs were statistically analyzed using the student t test. The brain tissue was removed immediately for light and electron microscopy examination if the lesion showed no contrast enhancement and was isointense on DWIs and the ADC maps. RESULTS: The lesions appeared at 1 hour in both groups as contrast enhancement on Gd-T1WIs, as isointensity or mild hyperintensity on DWIs, and as isointensity on the ADC maps. On day 1, these MRI findings were decreased in group 1 and were not seen in group 2. At 1 hour, the SIRs of group 1 were significantly higher than those of group 2 (P = 0.016). On day 1, the SIRs of both groups approximated 1.0. Light microscopy findings revealed minor necrosis and demyelination in one cat from group 1 and in 3 cats from group 2. Electron microscopy examinations showed minimal findings in the cortical lesions in groups 1 and 2. CONCLUSIONS: Infusion of unsaturated fatty acid emulsion into the carotid artery of cats revealed vasogenic edema of the brain and reversible changes as depicted on MRI. This unsaturated fat emulsion technique may be used as a model for research on BBB disruption.

Animals↗
PubMed1998

Transillumination mapping prior to ambulatory phlebectomy.

BACKGROUND: Ambulatory phlebectomy (AP) for removal of varicose and reticular veins has become a very popular and widely used in-office outpatient technique over the past decade. One of the major obstacles of this or any other surgical vein removal technique is the technical difficulty presented to the surgeon by the disappearance of the veins to be removed when the patient is positioned horizontally on an operative table. Preoperative marking is therefore essential. OBJECTIVE: To investigate whether use of transillumination would facilitate and enhance marking of varicose veins prior to AP, we performed a study in which both traditional marking with the patient standing and transillumination marking with the patient horizontal were performed sequentially. METHODS: One hundred patients were sequentially examined prior to AP. The veins to be removed were mapped by the traditional way utilizing visual inspection and palpation in a standing position. They were then mapped in the supine or prone position utilizing a transillumination device specifically designed to enhance visualization of veins prior to venipuncture. RESULTS: In 100 out of 100 patients the markings performed using transillumination mapping most closely correlated with actual vein position during surgery. In addition, transillumination allowed for gauging of vein depth. CONCLUSIONS: Transillumination mapping significantly enhances the technique of ambulatory phlebectomy by more accurately visualizing the course of a varicose vein prior to extraction. Furthermore, sites for incisions or punctures are more accurately guided. As a result of this experience, it is now our routine practice to perform preoperative mapping for AP by transillumination in the horizontal position.

Ambulatory Surgical Procedures↗
PubMed2005

The mammalian formin FHOD1 interacts with the ERK MAP kinase pathway.

Formin homology 2 domain containing protein (FHOD1), a mammalian formin, regulates cytoskeletal architecture, enhances cell migration, and induces gene expression from the serum response element. In this study, we describe co-precipitation of FHOD1 with components of the ERK MAP kinase pathway while co-precipitation of FHOD1 with p38 MAP kinase and JNK was not observed. In addition, FHOD1 co-localized to lamellipodia with Raf-1 and to stress fibers with MEK. FHOD1-induced gene expression from the serum response element was dependent on ERK MAP kinase activation, and the native skeletal actin promoter were activated by FHOD1 through the SRF site. However, FHOD1-induced stress-fiber formation and gene expression from the skeletal actin promoter was independent of ERK activation. These novel data demonstrate that FHOD1-ERK MAP kinase interaction regulates key aspects of FHOD1 biology.

Animals↗
PubMed2002

A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity.

A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance: sek-1, which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase. RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense. These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species.

Animals↗
PubMed1991

Assembly properties of tubulin after carboxyl group modification.

By chemically modifying carboxyl groups we have investigated the role of the highly acidic COOH-terminal domains of alpha- and beta-tubulin in regulating microtubule assembly. Using a carbodiimide-promoted amidation reaction, as many as 25 carboxyl groups were modified by the addition of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and an amine nucleophile, [14C] glycine ethyl ester or [3H]methylamine, to assembled microtubules. Modification occurred primarily in the carboxyl-terminal region as demonstrated by limited proteolysis of modified tubulin by trypsin, chymotrypsin, subtilisin, and carboxypeptidase Y. Modified tubulin polymerized into microtubules with a critical concentration that was 15% of that for unmodified tubulin. Assembly of modified tubulin and microtubules formed from modified tubulin were less sensitive to Ca2+ and high ionic strength. Ca2+ binding studies under low ionic strength conditions indicated that modified tubulin does not contain the high affinity Ca2+ binding site. While assembly of unmodified tubulin was stimulated by Mg2+ up to 10 mM, assembly of the modified protein was inhibited by concentrations greater than 1 mM. When 24 residues were modified, polymerization was no longer stimulated by microtubule-associated proteins (MAPs) or polylysine and incorporation of high molecular weight MAPs into the polymers was reduced by about 70% compared to unmodified tubulin. These studies demonstrate that chemical modification of carboxyl groups in tubulin, most of which are localized in the COOH-terminal region, leads to an enhanced ability to polymerize and a decrease in interaction with MAPs and other positively charged species.

Animals↗
PubMed2002

A gain-of-function mutation in an Arabidopsis Toll Interleukin1 receptor-nucleotide binding site-leucine-rich repeat type R gene triggers defense responses and results in enhanced disease resistance.

In a screen for suppressors of npr1-5-based salicylic acid (SA) insensitivity, we isolated a semidominant gain-of-function mutation, designated ssi4, that confers constitutive expression of several PR (pathogenesis-related) genes, induces SA accumulation, triggers programmed cell death, and enhances resistance to bacterial and oomycete pathogens. Through map-based cloning, ssi4 was identified and found to encode a putative protein belonging to the TIR-NBS-LRR (Toll Interleukin1 Receptor-Nucleotide Binding Site-Leu-Rich Repeat) class of R (resistance) proteins. Comparison between ssi4 and the corresponding wild-type sequence revealed a single amino acid substitution in the NBS. Epistasis analysis indicated that SA and EDS1 are required for ssi4-induced PR-1 expression and enhanced disease resistance; they also are required for the increased accumulation of SSI4 and EDS1 transcripts detected in the ssi4 mutant. Although high levels of ssi4 transcripts correlate with the appearance of the mutant phenotype, overexpression of the wild-type SSI4 gene failed to induce stunting, spontaneous lesion formation, or increased PR-1 expression associated with the ssi4 mutation. Thus, the ssi4 phenotype does not appear to be caused by overexpression of this R gene; rather, we propose that the NBS substitution generates a constitutively activated R protein. Furthermore, because SA treatment induced the expression of SSI4 and the closely related TIR-NBS-LRR genes RPP1 and RPS4 but had little effect on the expression of the coiled-coil NBS-LRR genes RPM1 and RPS2, we suggest that SA not only functions as a critical signal for downstream resistance events but also upregulates the expression of certain R genes.

Amino Acid Sequence↗
PubMed2005

Enhanced transmission of light through a circularly structured aperture.

Using the differential theory of light diffraction by finite cylindrical objects, we study light transmission through a small circular aperture in a metallic screen with concentric corrugation around the nanohole. Poynting vector maps in the region below the screen show that the field enhancement compared with an unstructured aperture is obtained with corrugation lying on the entrance face of the screen. Corrugation on the exit face leads to a more directional radiation close to the normal to the screen. The spectral dependence of the transmission shows a sharp maximum linked with surface plasmon excitation.

Journal Article↗
PubMed1992

Subchronic methamphetamine treatment enhances ouabain-induced striatal dopamine efflux in vivo.

The effect of manipulation of the Na+ gradient between the intracellular and extracellular media on striatal dopamine (DA) efflux under steady-state conditions after subchronic methamphetamine (MAP) treatment was investigated. Rats were injected with 4 mg/kg MAP or saline (i.p.), once daily for 14 days. Seven days after the last injection, ouabain (10(-4) M), a selective inhibitor of the Na+,K(+)-ATPase, was infused locally through a semi-permeable probe in the striatum. Ouabain induced a significantly greater (P less than 0.01) increase of the DA concentrations in the striatal perfusate in the subchronic MAP than the control group. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) (P less than 0.05) and 5-hydroxyindoleacetic acid (5-HIAA) (P less than 0.05) were significantly higher in the subchronic MAP than in the control group. Reserpine pretreatment (5 mg/kg, i.p.) did not affect the enhanced ouabain-induced DA efflux (P less than 0.01) in the subchronic MAP group, and the levels of DOPAC (P less than 0.01), 5-HIAA (P less than 0.01) and HVA (P less than 0.01) were also significantly higher in the subchronic MAP than in the control group. In contrast, alpha-methyl-p-tyrosine (250 mg/kg, i.p.) pretreatment abolished the ouabain-induced efflux of DA, DOPAC and HVA, but not 5-HIAA, in both groups. Specific striatal [3H]ouabain binding and striatal Na+,K(+)-ATPase activity in the subchronic MAP and control groups did not differ significantly. These results suggest that subchronic MAP treatment facilitates the efflux of newly synthesized DA, which is induced by the ouabain-induced decrease of the Na+ gradient between intracellular and extracellular media.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

The differential regulation of group II(A) and group V low molecular weight phospholipases A(2) in cultured rat astrocytes.

In astrocytes, cytokines stimulate the release of secretory phospholipase A(2) (sPLA(2)) activity and group II(A) sPLA(2) expression. This paper reports that two sPLA(2) isoforms, group II(A) and group V, are in fact expressed by astrocytes. Our studies showed that tumor necrosis factor alpha (TNFalpha) enhanced the mRNA of both isoforms, but the time courses of enhancement differed; group V was induced much faster than group II(A). Moreover, TNFalpha stimulated both the NF-kappaB and mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase, c-Jun NH(2)-terminal kinase, and p38 MAP kinase) signaling pathways in astrocytes. Interestingly, PI 3-kinase activity also was enhanced by TNFalpha, and NF-kappaB pathway was involved in mediating its effect. Specific inhibitors were used to show that both extracellular signal-regulated kinase and p38 MAP kinase may contribute to the effect of TNFalpha and that blocking phosphatidylinositol 3-kinase activity fully reversed the effect of TNFalpha. Furthermore, in astrocytes, TNFalpha-induced release of sPLA(2) activity was partially reversed by thyroid hormone and almost abolished by growth factors. This phenomenon was accompanied by a less marked increase in both group II(A) and group V sPLA(2) mRNA. In the presence of growth factors, the increase in group V mRNA was inhibited early and transiently, in contrast to what was observed with group II(A), which was more persistently inhibited. Although a transcriptional effect of thyroid hormone or growth factors in astrocytes cannot be definitively excluded, both types of factor interfered with sPLA(2) expression in a manner suggesting the existence of regulation of post-transcriptional events.

Animals↗
PubMed1997

Cardiovascular and renal actions of the endothelin(B) receptor in pigs.

Previously we showed that blocking the endothelin (ET)A receptor subtype with BQ-153 inhibited the vasoconstrictor effects of intravenously administered ET-1. In the presence of the ET(A) antagonist, ET-1 produced marked reductions in myocardial contractility and renal blood flow. We postulated that either the ET(B) receptor, or some other, as yet unidentified, ET-receptor subtype mediated the observed hemodynamic changes. In anesthetized pigs, this hypothesis was tested by using a recently developed selective, high-affinity antagonist to the ET(B) receptor, BQ-788, and sarafotoxin S6c, a selective ET(B) agonist, to determine the contribution of this receptor subtype to cardiovascular function. Endothelin-1 (0.4 nmol/kg, i.v.) produced the characteristic biphasic hemodynamic responses, consisting of an initial transient reduction in mean arterial pressure (MAP; 83 +/- 3 to 72 +/- 4 mm Hg; n = 9) followed by a prolonged increase (112 +/- 4 mm Hg; p < 0.01). As well, cardiac output (-58%; p < 0.05), myocardial contractility (-19%; p < 0.01), and renal blood flow (63%; p < 0.05) decreased. Sarafotoxin S6c produced marked but transient reductions in MAP (p < 0.001), cardiac output (p < 0.01), myocardial contractility (p < 0.001), and renal blood flow (p < 0.05). BQ-788 (1.0 mg/kg, i.v.), administered 3 min before sarafotoxin S6c, inhibited its effects. BQ-788 also inhibited the initial transient reduction in MAP seen after the injection of ET-1, but the subsequent sustained pressor responses were enhanced as reflected in the greater increases in left ventricular pressure (p < 0.02), myocardial contractility (p < 0.05), MAP (p < 0.01), and a larger reduction in cardiac output (p < 0.05). The heart rate was not changed after the initial ET injection, but it increased 54% when the peptide was administered in the presence of BQ-788. The reduction in renal blood flow was still evident, and its magnitude (64%) remained the same (p < 0.01) after treatment with BQ-788. Only the combined administration of both the ET(A) (BQ-123) and ET(B) (BQ-788) receptor antagonists blocked the effects of ET-1 on renal blood flow (p < 0.05). These data confirm that BQ-788 is a selective and effective antagonist of the ET(B) receptor and show that activation of this receptor subtype is involved in the transient vasodilation provoked by ET-1. Additionally, the ET(B) receptor appears to oppose the vasoconstrictor effects of the ET(A) receptor, which clearly mediates vasoconstriction. Combined treatment with BQ-123 and BQ-788 attenuated the reductions in renal blood flow produced by ET-1. Furthermore, some actions of ET-1 were not blocked by these antagonists and cannot be attributed to either the ET(A) or ET(B) receptors. We hypothesize the existence of an additional ET receptor or a subtype of the ET(B) receptor that is insensitive to BQ-788.

Animals↗
PubMed2004

Glucocorticoids synergize with IL-1beta to induce TLR2 expression via MAP Kinase Phosphatase-1-dependent dual Inhibition of MAPK JNK and p38 in epithelial cells.

BACKGROUND: Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, their role in enhancing host immune and defense response against invading bacteria is poorly understood. Toll-like receptor 2 (TLR2) has recently gained importance as one of the major host defense receptors. The increased expression of TLR2 in response to bacteria-induced cytokines has been thought to be crucial for the accelerated immune response and resensitization of epithelial cells to invading pathogens. RESULTS: We show that IL-1beta, a key proinflammatory cytokine, greatly up-regulates TLR2 expression in human epithelial cells via a positive IKKbeta-IkappaBalpha-dependent NF-kappaB pathway and negative MEKK1-MKK4/7-JNK1/2 and MKK3/6-p38 alpha/beta pathways. Glucocorticoids synergistically enhance IL-1beta-induced TLR2 expression via specific up-regulation of the MAP kinase phosphatase-1 that, in turn, leads to dephosphorylation and inactivation of both MAPK JNK and p38, the negative regulators for TLR2 induction. CONCLUSION: These results indicate that glucocorticoids not only suppress immune and inflammatory response, but also enhance the expression of the host defense receptor, TLR2. Thus, our studies may bring new insights into the novel role of glucocorticoids in orchestrating and optimizing host immune and defense responses during bacterial infections and enhance our understanding of the signaling mechanisms underlying the glucocorticoid-mediated attenuation of MAPK.

Blotting, Western↗
PubMed2000

fMRI of visual system activation in the conscious rabbit.

A conscious rabbit preparation developed for fMRI, and the results from visual stimulation studies at a 4.7T magnetic field are described. The rabbit is ideal for these experiments because of its natural tolerance for restraint. High spatial and temporal resolution magnetic resonance images, without movement artifacts, were obtained during long periods of restraint. Functional activation in primary visual cortex and lateral geniculate nucleus (LGN) were reproducibly observed in response to light stimulus. In comparison to existing anesthetized animal models, a functional response free of the anesthetic modulation can be recorded with the new approach. The conscious animal model can be applied to functional studies of sensory systems, learning and memory, and drug-induced cerebral activation.

Animals↗
PubMed1990

Single fiber studies of ascending input to the cuneate nucleus of cats: I. Morphometry of primary afferent fibers.

The morphology of afferent fibers ascending to the cuneate nucleus has been examined in this and the subsequent paper in order to quantify the pattern of arborization and bouton arrangement of selected classes of primary afferents and to compare these data with data from postsynaptic fibers ascending to the cuneate nucleus. Electrophysiologically identified G hair and Ia muscle afferent fibers in the cuneate fasciculus were intraaxonally injected with horseradish peroxidase. Cutaneous afferents terminated dorsal to proprioceptive afferents, especially at middle levels of the cuneate nucleus. The spacing of collaterals along G hair fibers was variable, but averaged 1.46 collaterals per mm; collateral density was higher at middle cuneate levels than in the rest of the nucleus. Collateral density of Ia fibers was lower than for G hair fibers and was lowest at caudal levels of the nucleus. Branches of G hair collaterals, though often initially diverging, usually converged to terminate in a single focus in the dorsal part of the nucleus. The probability of bifurcation of Ia collaterals decreased steadily at successive branch points. These collaterals branched less symmetrically than G hair collaterals, and terminated in the ventral cuneate with less dense arbors, stretched mediolaterally, but of comparable cross-sectional area. Individual G hair collaterals gave rise to more boutons than Ia collaterals; in both cases they were mostly of the en passant type. Boutons were restricted to distal branches of G hair collaterals, whereas boutons of Ia collaterals were also located on proximal branches. Bouton size was similar for the two classes of collaterals. The data reported here, in combination with the published literature, suggest that the collaterals of roughly 300 G hair fibers overlap at any given point at middle levels of the cuneate nucleus. This high degree of anatomical convergence is not predicted by the functional segregation described with electrophysiological mapping, implying the presence of intrinsic nuclear mechanisms enhancing response specificity.

Afferent Pathways↗