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E Schnell

Publications and source records attributed to E Schnell.

At least 19 recordsLinked to original sources
PubMed2001

Hippocampal synaptic transmission and plasticity are preserved in myosin Va mutant mice.

Recent studies have identified myosin Va as an organelle motor that may have important functions in neurons. Abundantly expressed at the hippocampal postsynaptic density, it interacts with protein complexes involved in synaptic plasticity. It is also located in presynaptic terminals and may function to recruit vesicles in the reserve pool to the active zone. Dilute-lethal mice are spontaneous myosin Va mutants and have severe neurological symptoms. We studied hippocampal physiology at CA3-CA1 excitatory synapses in dilute-lethal mutant mice to test the hypothesis that myosin Va plays a role in pre- or postsynaptic elements of synaptic transmission. In all assays performed, the mutant synapses appeared to be functioning normally, both pre- and postsynaptically. These data suggest that myosin Va is not essential for the synaptic release machinery, postsynaptic receptor composition, or plasticity at this synapse, but does not exclude significant roles for myosin Va in other cell types nor potential compensation by other myosin V isoforms.

Animals↗
PubMed2000

PSD-95 involvement in maturation of excitatory synapses.

PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also enhanced maturation of the presynaptic terminal. These effects required synaptic clustering of PSD-95 but did not rely on its guanylate kinase domain. PSD-95 expression also increased the number and size of dendritic spines. These results demonstrate that PSD-95 can orchestrate synaptic development and are suggestive of roles for PSD-95 in synapse stabilization and plasticity.

Animals↗
PubMed2000

The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB.

The neurotrophin BDNF has been shown to modulate long-term potentiation (LTP) at Schaffer collateral-CA1 hippocampal synapses. Mutants in the BDNF receptor gene trkB and antibodies to its second receptor p75NTR have been used to determine the receptors and cells involved in this response. Inhibition of p75NTR does not detectably reduce LTP or affect presynaptic function, but analyses of newly generated trkB mutants implicate TrkB. One mutant has reduced expression in a normal pattern of TrkB throughout the brain. The second mutant was created by cre-loxP-mediated removal of TrkB in CA1 pyramidal neurons of this mouse. Neither mutant detectably impacts survival or morphology of hippocampal neurons. TrkB reduction, however, affects presynaptic function and reduces the ability of tetanic stimulation to induce LTP. Postsynaptic glutamate receptors are not affected by TrkB reduction, indicating that BDNF does not modulate plasticity through postsynaptic TrkB. Consistent with this, elimination of TrkB in postsynaptic neurons does not affect LTP. Moreover, normal LTP is generated in the mutant with reduced TrkB by a depolarization-low-frequency stimulation pairing protocol that puts minimal demands on presynaptic terminal function. Thus, BDNF appears to act through TrkB presynaptically, but not postsynaptically, to modulate LTP.

Animals↗
PubMed2000

Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering.

Postsynaptic density-95 (PSD-95/SAP-90) is a palmitoylated peripheral membrane protein that scaffolds ion channels at excitatory synapses. To elucidate mechanisms for postsynaptic ion channel clustering, we analyzed the cellular trafficking of PSD-95. We find that PSD-95 transiently associates with a perinuclear membranous compartment and traffics with vesiculotubular structures, which migrate in a microtubule-dependent manner. Trafficking of PSD-95 with these vesiculotubular structures requires dual palmitoylation, which is specified by five consecutive hydrophobic residues at the NH(2) terminus. Mutations that disrupt dual palmitoylation of PSD-95 block both ion channel clustering by PSD-95 and its synaptic targeting. Replacing the palmitoylated NH(2) terminus of PSD-95 with alternative palmitoylation motifs at either the NH(2) or COOH termini restores ion channel clustering also induces postsynaptic targeting, respectively. In brain, we find that PSD-95 occurs not only at PSDs but also in association with intracellular smooth tubular structures in dendrites and spines. These data imply that PSD-95 is an itinerant vesicular protein; initial targeting of PSD-95 to an intracellular membrane compartment may participate in postsynaptic ion channel clustering by PSD-95.

Animals↗
PubMed2000

Biodegradable poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether diblock copolymers: structures and surface properties relevant to their use as biomaterials.

To obtain biodegradable polymers with variable surface properties for tissue culture applications, poly(ethylene glycol) blocks were attached to poly(lactic acid) blocks in a variety of combinations. The resulting poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether (Me.PEG-PLA) diblock copolymers were subject to comprehensive investigations concerning their bulk microstructure and surface properties to evaluate their suitability for drug delivery applications as well as for the manufacture of scaffolds in tissue engineering. Results obtained from 1H-NMR, gel permeation chromatography, wide angle X-ray diffraction and modulated differential scanning calorimetry revealed that the polymer bulk microstructure contains poly(ethylene glycol)-monomethyl ether (Me.PEG) domains segregated from poly(D,L-lactic acid) (PLA) domains varying with the composition of the diblock copolymers. Analysis of the surface of polymer films with atomic force microscopy and X-ray photoelectron spectroscopy indicated that there is a variable amount of Me.PEG chains present on the polymer surface, depending on the polymer composition. It could be shown that the presence of Me.PEG chains in the polymer surface had a suppressive effect on the adsorption of two model peptides (salmon calcitonin and human atrial natriuretic peptide). The possibility to modify polymer bulk microstructure as well as surface properties by variation of the copolymer composition is a prerequisite for their efficient use in the fields of drug delivery and tissue engineering.

Biocompatible Materials↗
PubMed1999

Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release.

Rab3A and rab3C are GTP-binding proteins of synaptic vesicles that regulate vesicle exocytosis. Rabphilin is a candidate rab3 effector at the synapse because it binds to rab3s in a GTP-dependent manner, it is co-localized with rab3s on synaptic vesicles, and it dissociates with rab3s from the vesicles during exocytosis. Rabphilin contains two C(2) domains, which could function as Ca(2+) sensors in exocytosis and is phosphorylated as a function of stimulation. However, it is unknown what essential function, if any, rabphilin performs. One controversial question regards the respective roles of rab3s and rabphilin in localizing each other to synaptic vesicles: although rabphilin is mislocalized in rab3A knock-out mice, purified synaptic vesicles were shown to require rabphilin for binding of rab3A but not rab3A for binding of rabphilin. To test whether rabphilin is involved in localizing rab3s to synaptic vesicles and to explore the functions of rabphilin in regulating exocytosis, we have now analyzed knock-out mice for rabphilin. Mice that lack rabphilin are viable and fertile without obvious physiological impairments. In rabphilin-deficient mice, rab3A is targeted to synaptic vesicles normally, whereas in rab3A-deficient mice, rabphilin transport to synapses is impaired. These results show that rabphilin binds to vesicles via rab3s, consistent with an effector function of rabphilin for a synaptic rab3-signal. Surprisingly, however, no abnormalities in synaptic transmission or plasticity were observed in rabphilin-deficient mice; synaptic properties that are impaired in rab3A knock-out mice were unchanged in rabphilin knock-out mice. Our data thus demonstrate that rabphilin is endowed with the properties of a rab3 effector but is not essential for the regulatory functions of rab3 in synaptic transmission.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Librarians' use of HealthWeb for reference and instruction.

HealthWeb is a selective Internet resource that links users to annotated, evaluated Internet resources in the health sciences. A collaborative effort of librarians from more than twenty academic institutions, it is a valuable tool for librarians at the Reference Desk and during instruction sessions. Contents of the Reference Resources section are highlighted, as well as an example of use of the Nursing page during a typical class.

Academic Medical Centers↗
PubMed1995

Dynamics of learning and recall at excitatory recurrent synapses and cholinergic modulation in rat hippocampal region CA3.

Hippocampal region CA3 contains strong recurrent excitation mediated by synapses of the longitudinal association fibers. These recurrent excitatory connections may play a dominant role in determining the information processing characteristics of this region. However, they result in feedback dynamics that may cause both runaway excitatory activity and runaway synaptic modification. Previous models of recurrent excitation have prevented unbounded activity using biologically unrealistic techniques. Here, the activation of feedback inhibition is shown to prevent unbounded activity, allowing stable activity states during recall and learning. In the model, cholinergic suppression of synaptic transmission at excitatory feedback synapses is shown to determine the extent to which activity depends upon new features of the afferent input versus components of previously stored representations. Experimental work in brain slice preparations of region CA3 demonstrates the cholinergic suppression of synaptic transmission in stratum radiatum, which contains synapses of the longitudinal association fibers.

Animals↗
PubMed1994

Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology.

ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01-500 microM) on synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus-evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 microM. At 100 microM, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1% in s. l-m. The muscarinic antagonist atropine (1 microM) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations.

Animals↗
PubMed1990

Overexpression of the pseudoautosomal gene MIC2 in Ewing's sarcoma and peripheral primitive neuroectodermal tumor.

Ewing's Sarcoma (ES), the second most frequent bone tumor in childhood and adolescence, and the probably closely related peripheral primitive neuroectodermal tumor (pPNET) share a unique cytogenetic translocation between chromosomes 11 and 22. Both of them expose high amounts of a glycoprotein on their cell surface, which can be specifically detected by the mAb HBA-71. The cDNA coding for the HBA-71 antigen was isolated by screening a cDNA expression library constructed from a pPNET-derived cell line. Nucleotide sequencing revealed the HBA-71 antigen to be the product of the pseudoautosomal gene MIC2 previously identified by the mAb 12E7 in haematopoietic cells. This antigen is a glycoprotein with a molecular weight of about 29,000 and is expressed in low amounts in most human cell lines and probably normal tissues and tumors with only a few exceptions. In T-cells the antigen is involved in cell adhesion processes. In ES- and pPNET-derived cell lines MIC2 expression is significantly enhanced. No gross changes in posttranslational modification could be observed. The high expression results in easy and specific detection of the antigen in immunocytochemical analysis of paraffin embedded tissue sections making HBA-71 a useful tool in tumor diagnosis.

12E7 Antigen↗
PubMed1985

[Benefits of routine automatic blood picture differentiation].

The benefits of automated blood smear differential cell counting as a supplementary laboratory examination have been studied. The investigations focussed on patients of whom hematology requisitions were limited to total leukocyte count and hemoglobin determination. The specimens were derived from patients of departments of surgery and obstetrics and gynecology. For specimen collection the vacutainer system was used. The blood smears were prepared in a Coulter Electronics slide spinner, stained with a Hematek II slide stainer and analyzed in the Coulter Electronics Diff 3-50 cell classifier. A total of 1700 blood smears were examined. Following processing of each sample, the classification of each cell was inspected. Corrections were performed, if necessary, and the number of classification changes performed for each smear was registered. Using the in-house normal ranges, 34.5% were pathological smears. Since this group included a large number of borderline cases, new discrimination limits for clinically relevant pathological findings were set empirically. According to these wider ranges, the fraction of pathological slides amounted to 15.2%. Among these, immature granulocytes, eosinophilia and lymphopenia were the most frequent pathological findings. Microscopic control proved in 57.6% of the total number of smears. This complemental procedure was not found to be time-consuming.

Automation↗
PubMed1983

[Automatic blood smear differentiation using the Coulter Electronics Diff 3-50 system].

The Coulter Electronics Diff 3-50 consists of a slide spinner, a slide stainer and a cell classifier. The cell analyzer is composed of an optical system with a microscope, microprocessor, video camera and printer. The system used in this laboratory is supplemented by a video monitor. The Diff 3-50 analyzes blood cells according to the classical criteria used in hematology. It classifies 11 types of nucleated blood cells and it processes an average of 45 blood smears per hour. It features a visual control of each cell classified with a built-in mechanism for change of classification by the operator if necessary. Moreover, the system estimates leukocyte and platelet count and generates a quantitative estimate of platelet number. Blood smears of 507 blood samples from patients admitted to the hospital were included in the present study. They were analyzed twice, first by the Diff 3-50, and secondly by visual checking of the automatic classification of each cell. The results of the two procedures were then compared. The findings indicate an overall false negative error of 1.4% and an overall false positive error of 4.3%. Major differences were found, though not consistently, only when the classification by the Diff 3-50 of the band neutrophils was compared with the visual classification performed by the operator. Lymphocytes and monocytes correlated well when both procedures were compared. Blasts present in 5 blood smears were recognized by the classifier. The Diff 3-50 identified immature granulocytes in 47 out of 48 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cell Count↗