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PubMed1998

Neurogenesis in the thoracic neuromeres of two crustaceans with different types of metamorphic development

The mode of embryonic and larval development and the ethology of metamorphosis in the spider crab and the American lobster are very different, and we took advantage of this to compare neuronal development in the two species. The goals of this study were to discover whether the differences in the maturation of the neuromuscular system in the pereopods and the metamorphic changes of motor behavior between the two species are reflected at the level of the developing nervous system ('neurometamorphosis'). Furthermore, we wanted to broaden our understanding of the mechanisms that govern neuronal development in arthropods. Proliferation of neuronal stem cells in thoracic neuromeres 4-8 of the lobster Homarus americanus and the crab Hyas araneus was monitored over the course of embryonic and larval development using the in vivo incorporation of bromodeoxyuridine (BrdU). Neuropil structure was visualized using an antibody against Drosophila synapsin. While proliferation of neuronal precursors has ceased when embryogenesis is 80 % complete (E80%) in the lobster thoracic neuromeres, proliferation of neuroblasts in the crab persists throughout embryonic development and into larval life. The divergent temporal patterns of neurogenesis in the two crustacean species can be correlated with differences in larval life style and in the degree of maturation of the thoracic legs during metamorphic development. Several unusual aspects of neurogenesis reported here distinguish these crustaceans from other arthropods. Lobsters apparently lack a postembryonic period of proliferation in the thoracic neuromeres despite the metamorphic remodeling that takes place in the larval stages. In contrast, an increase in mitotic activity towards the end of embryonic development is found in crabs, and neuroblast proliferation persists throughout the process of hatching into the larval stages. In both E20% lobster embryos and mid-embryonic crabs, expression of engrailed was found in a corresponding set of neurons and putative glial cells at the posterior neuromere border, suggesting that these cells have acquired similar specific identities and might, therefore, be homologous. None of the BrdU-labeled neuroblasts (typically 6-8 per hemineuromere over a long period of embryogenesis) was positive for engrailed at this and subsequent stages. Our findings are discussed in relation to the spatial and temporal patterns of neurogenesis in insects.

Journal Article↗
PubMed2002

Glomerular representation of plant volatiles and sex pheromone components in the antennal lobe of the female Spodoptera littoralis.

We studied the projection patterns of antennal lobe (AL) interneurones sensitive to plant volatiles and female-produced sex pheromone components in the female moth, Spodoptera littoralis. Ten compounds (eight plant-derived compounds and two sex pheromone components) were singly applied to the antenna and, using intracellular recording and staining techniques, the physiological and morphological characteristics of responding neurones were investigated. In addition, ALs stained with a synapsin antibody were optically sectioned using confocal microscopy, and a three-dimensional map of glomeruli in the anterior aspect of the AL was reconstructed. We used the map as a reference for identification of glomeruli innervated by projection neurones (PNs) that respond to plant volatiles and/or pheromone components. Nineteen PNs, responding to one to seven compounds of the ten tested stimuli, were stained with neurobiotin. These neurones each arborised in a single glomerulus in the frontal side of the AL. PNs responding to the same compound arborised in different glomeruli and PNs arborising in the same glomerulus responded to different compounds. Accordingly, glomeruli harbouring the dendritic arborisations of PNs responding to each of the tested compounds constituted a unique array of glomeruli that were not necessarily adjacent. It was thus clear that, at the output level, a single plant volatile or a sex pheromone component was not represented within a single glomerulus in the AL. We expect complex patterns of glomeruli to be involved in the coding of plant-derived compounds, as well as sex pheromone components, in female S. littoralis.

Animals↗
PubMed1991

Autophosphorylation of Ca2+/calmodulin-dependent protein kinase II: effects on interaction between enzyme and substrate.

Characteristics of the autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) from the cytosol and in the postsynaptic densities (PSD) of rat brain were investigated. Several proteins were surveyed for their abilities to serve as a substrate for non-autophosphorylated and autophosphorylated CaM kinase IIs from the cytosol and PSD. The tested substrates were separated into two groups. Autophosphorylation of the kinase slightly decreased or did not change its activities towards substrates of the first group: myosin light chain of chicken gizzard, synapsin I, tau factor and microtubule-associated protein 2. In contrast, autophosphorylation of the enzyme increased its activities towards substrates of the second group: syntide-2, histone H1, calcineurin and myelin basic protein. The Ca2+/calmodulin-independent kinase activity increased by autophosphorylation with any of substrates tested. Similar results were obtained with the cytosolic and PSD CaM kinase II. Trifluoperazine and mastoparan, calmodulin binding antagonists, inhibited the activity of the non-autophosphorylated CaM kinase II, but had no effect or only a slight inhibitory effect on the activity of the autophosphorylated CaM kinase II, indicating that the autophosphorylated kinase has no requirement for calmodulin for Ca(2+)-dependent activity and/or a higher affinity for calmodulin The results suggest that the autophosphorylation of CaM kinase II is a subtle mechanism for regulating the interaction between the enzyme and substrate.

Animals↗
PubMed1996

Prolylendopeptidase inhibitory activity of a glial fibrillary acidic protein fragment and other proline-rich peptides.

The brain prolylendopeptidase (PEP) inhibitory activity of synthetic peptides related to the bovine brain-derived PEP inhibitor, GFAP-(38-55) (MPPPLPARVDFSLAGALN), was investigated. Homologous peptides such as MPPPLPTRVDFSLAGALN (human type) and MTPPLPARVDFSLAGALN (mouse type) also inhibited PEP. Among various synthetic fragments of GFAP-(38-55), only MPPPLP had a Ki essentially the same as that of GFAP-(38-55). Similar synthetic proline-rich peptides such as synapsin fragments and SH3 domain-binding peptides had more or less inhibitory activity.

Amino Acid Sequence↗
PubMed2005

Microarray and real-time PCR analyses of gene expression in the honeybee brain following caffeine treatment.

To test the idea that caffeine might induce changes in gene expression in the honeybee brain, we contrasted the transcriptional profiles of control and caffeine-treated brains using high-throughput cDNA microarrays. Additional quantitative real-time PCR was performed on a subset of eight transcripts to visualize the temporal changes induced by caffeine. Genes that were significantly upregulated in caffeine-treated brains included those involved in synaptic signaling (GABA:Na symporter, dopamine D2R-like receptor, and synapsin), cytoskeletal modifications (kinesin and microtubule motors), protein translation (ribosomal protein RpL4, elongation factors), and calcium-dependent processes (calcium transporter, calmodulin- dependent cyclic nucleotide phosphodiesterase). In addition, our study uncovered a number of novel, caffeine-inducible genes that appear to be unique to the honeybee. Time-dependent profiling of caffeine-sensitive gene expression shows significant upregulation 1 h after treatment followed by moderate downregulation after 4 h with no additional changes occuring after 24 h. Our results provide initial evidence that the dopaminergic system and calcium exchange are the main targets of caffeine in the honeybee brain and suggest that molecular responses to caffeine in an invertebrate brain are similar to those in vertebrate organisms.

Animals↗
PubMed1993

Pathobiochemical aspects of cytoskeleton components.

This review summarizes pathobiochemical aspects of diseases, in which cytoskeletal components play a crucial role in pathogenesis. An attempt to classify the disorders on the basis of phenotypic changes that occur in microfilaments, intermediate filaments and microtubuli was unsuccessful. Three groups of disorders are presented: 1. cytoplasmic inclusions in specific diseases (merely descriptive); 2. diseases with genetic defects in cytoskeletal proteins (a chain of causality from defect to phenotype, in some cases with large gaps); 3. diseases with suspected involvement of cytoskeleton (hypothetical causal chain). Microfilaments are involved in certain pathogenetic processes on account of defects in their associated proteins; in Duchenne muscular dystrophy, dystrophin is defective, while the defective protein in Rett syndrome is synapsin. Defects in spectrin and membrane anchor proteins lead to disorders of the red cell membrane skeleton (congenital haemolytic anaemias). Intermediate filaments accumulate in some types of cytoplasmic inclusions, together with ubiquitin (Mallory bodies, desmin accumulation in some myopathies and others). A pathogenetic interpretation of this phenomenon is lacking. A genetic defect in certain types of keratin is the cause of epidermolysis bullosa. Interesting preliminary results are reviewed that reveal the crucial role of cytoskeletal components in a further group of diseases (intrahepatic cholestasis, Alzheimer disease, pemphigus). These disorders are currently under investigation, or are of theoretical interest with respect to the cytoskeleton. Specific reactions of cytoskeletal components in serum, which might be used diagnostically, have not been found.

Alzheimer Disease↗
PubMed2006

Separate populations of receptor cells and presynaptic cells in mouse taste buds.

Taste buds are aggregates of 50-100 cells, only a fraction of which express genes for taste receptors and intracellular signaling proteins. We combined functional calcium imaging with single-cell molecular profiling to demonstrate the existence of two distinct cell types in mouse taste buds. Calcium imaging revealed that isolated taste cells responded with a transient elevation of cytoplasmic Ca2+ to either tastants or depolarization with KCl, but never both. Using single-cell reverse transcription (RT)-PCR, we show that individual taste cells express either phospholipase C beta2 (PLCbeta2) (an essential taste transduction effector) or synaptosomal-associated protein 25 (SNAP25) (a key component of calcium-triggered transmitter exocytosis). The two functional classes revealed by calcium imaging mapped onto the two gene expression classes determined by single-cell RT-PCR. Specifically, cells responding to tastants expressed PLCbeta2, whereas cells responding to KCl depolarization expressed SNAP25. We demonstrate this by two methods: first, through sequential calcium imaging and single-cell RT-PCR; second, by performing calcium imaging on taste buds in slices from transgenic mice in which PLCbeta2-expressing taste cells are labeled with green fluorescent protein. To evaluate the significance of the SNAP25-expressing cells, we used RNA amplification from single cells, followed by RT-PCR. We show that SNAP25-positive cells also express typical presynaptic proteins, including a voltage-gated calcium channel (alpha1A), neural cell adhesion molecule, synapsin-II, and the neurotransmitter-synthesizing enzymes glutamic acid decarboxylase and aromatic amino acid decarboxylase. No synaptic markers were detected in PLCbeta2 cells by either amplified RNA profiling or by immunocytochemistry. These data demonstrate the existence of at least two molecularly distinct functional classes of taste cells: receptor cells and synapse-forming cells.

Animals↗
PubMed2005

Differential vesicular targeting and time course of synaptic secretion of the mammalian neurotrophins.

Neurotrophins are a family of secreted neuronal survival and plasticity factors comprising NGF, BDNF, neurotrophin-3 (NT-3), and NT-4. Whereas synaptic secretion of BDNF has been described, the routes of intracellular targeting and secretion of NGF, NT-3, and NT-4 in neurons are poorly understood. To allow for a direct comparison of intracellular targeting and release properties, all four mammalian neurotrophins were expressed as green fluorescent protein fusion proteins in cultured rat hippocampal neurons. We show that BDNF and NT-3 are targeted more efficiently to dendritic secretory granules of the regulated pathway of secretion (BDNF, in 98% of cells; NT-3, 85%) than NGF (46%) and NT-4 (23%). For all NTs, the remaining cells showed targeting to the constitutive secretory pathway. Fusing the BDNF pre-pro sequence to NT-4 directed NT-4 more efficiently to the regulated pathway of secretion. All neurotrophins, once directed to the regulated secretion pathway, were detected near synapsin I-positive presynaptic terminals and colocalized with PSD-95-DsRed (postsynaptic density-95-Discosoma red), suggesting postsynaptic targeting of the neurotrophins to glutamatergic synapses. Depolarization-induced release of all neurotrophins from synaptic secretory granules was slow (delay in onset, 10-30 s; tau = 120-307 s) compared with transmitter release kinetics monitored with FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)hexatrienyl)pyridinium dibromide] destaining (onset, <5 s; tau = 13 +/- 2 s). Among the neurotrophins, NT-4 secretion was most rapid but still proceeded 10 times more slowly than transmitter secretion. Preincubation of neurons with monensin (neutralizing intragranular pH, thus solubilizing the peptide core) increased the speed of secretion of BDNF, NGF, and NT-3 to the value of NT-4. These data suggest that peptide core dissolution in secretory granules is the critical determinant of the speed of synaptic secretion of all mammalian NTs and that the speed of release is not compatible with fast transmitter-like actions of neurotrophins.

Animals↗
PubMed2007

NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination.

Neurons and glia share a mutual dependence in establishing a functional relationship, and none is more evident than the process by which axons control myelination. Here, we identify LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) as a potent axonal inhibitor of oligodendrocyte differentiation and myelination that is regulated by nerve growth factor and its cognate receptor TrkA in a dose-dependent manner. Whereas LINGO-1 expressed by oligodendrocyte progenitor cells was previously identified as an inhibitor of differentiation, we demonstrate that axonal expression of LINGO-1 inhibits differentiation with equal potency. Disruption of LINGO-1 on either cell type is sufficient to overcome the inhibitory action and promote differentiation and myelination, independent of axon diameter. Furthermore, these results were recapitulated in transgenic mice overexpressing the full length LINGO-1 under the neuronal promoter synapsin. Myelination was greatly inhibited in the presence of enforced axonal LINGO-1. The implications of these results relate specifically to the development of potential therapeutics targeting extrinsic growth factors that may regulate the axonal expression of modulators of oligodendrocyte development.

Animals↗
PubMed2005

Spider peripheral mechanosensory neurons are directly innervated and modulated by octopaminergic efferents.

Octopamine is a chemical relative of noradrenaline providing analogous neurohumoral control of diverse invertebrate physiological processes. There is also evidence for direct octopaminergic innervation of some insect peripheral tissues. Here, we show that spider peripheral mechanoreceptors are innervated by octopamine-containing efferents. The mechanosensory neurons have octopamine receptors colocalized with synapsin labeling in the efferent fibers. In addition, octopamine enhances the electrical response of the sensory neurons to mechanical stimulation. Spider peripheral mechanosensilla receive extensive efferent innervation. Many efferent fibers in the legs of Cupiennius salei are GABAergic, providing inhibitory control of sensory neurons, but there is also evidence for other neurotransmitters. We used antibody labeling to show that some efferents contain octopamine and that octopamine receptors are concentrated on the axon hillocks and proximal soma regions of all mechanosensory neurons in the spider leg. Synaptic vesicles in efferent neurons were concentrated in similar areas. Octopamine, or its precursor tyramine, increased responses of mechanically stimulated filiform (trichobothria) leg hairs. This effect was blocked by the octopamine antagonist phentolamine. The octopamine-induced modulation was mimicked by 8-Br-cAMP, a cAMP analog, and blocked by Rp-cAMPS, a protein kinase A inhibitor, indicating that spider octopamine receptors activate adenylate cyclase and increase cAMP concentration. Frequency response analysis showed that octopamine increased the sensitivity of the trichobothria neurons over a broad frequency range. Thus, the major effect of octopamine is to increase its overall sensitivity to wind-borne signals from sources such as flying insect prey or predators.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2005

Does O-GlcNAc play a role in neurodegenerative diseases?

There are several lines of evidence that the modification of proteins by cytosolic- and nuclear-specific O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is closely related to neuropathologies, particularly Alzheimer's disease. Several neuronal proteins have been identified as being modified with O-GlcNAc; these proteins could form part of the inclusion bodies found, for example, in the most frequently observed neurologic disorder (i.e., Alzheimer's disease; Tau protein and beta-amyloid peptide are the well known aggregated proteins). O-GlcNAc proteins are also implicated in synaptosomal transport (e.g., synapsins and clathrin-assembly proteins). Inclusion bodies are partly characterized by a deficiency in the ubiquitin-proteasome system, avoiding the degradation of aggregated proteins. From this perspective, it appears interesting that substrate proteins could be protected against proteasomal degradation by being covalently modified with single N-acetylglucosamine on serine or threonine, and that the proteasome itself is modified and regulated by O-GlcNAc (in this case the turnover of neuronal proteins correlates with extracellular glucose). Interestingly, glucose uptake and metabolism are impaired in neuronal disorders, and this phenomenon is linked to increased phosphorylation. In view of the existence of the dynamic interplay between O-GlcNAc and phosphorylation, it is tempting to draw a parallel between the use of glucose, O-GlcNAc glycosylation and phosphorylation. Lastly, the two enzymes responsible for O-GlcNAc dynamism (i.e., O-GlcNAc transferase and glucosaminidase) are both enriched in the brain and genes that encode the two enzymes are located in two regions that are found to be frequently mutated in neurologic disorders. The data presented in this review strongly suggest that O-GlcNAc could play an active role in neurodegenerative diseases.

Acetylglucosamine↗
PubMed2005

Expression of neurodevelopmental markers by cultured porcine neural precursor cells.

Despite the increasing importance of the pig as a large animal model, little is known about porcine neural precursor cells. To evaluate the markers expressed by these cells, brains were dissected from 60-day fetuses, enzymatically dissociated, and grown in the presence of epidermal growth factor, basic fibroblast growth factor, and platelet-derived growth factor. Porcine neural precursors could be grown as suspended spheres or adherent monolayers, depending on culture conditions. Expanded populations were banked or harvested for analysis using reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, microarrays, and flow cytometry, and results compared with data from analogous human forebrain progenitor cells. Cultured porcine neural precursors widely expressed neural cell adhesion molecule (NCAM), polysialic acid (PSA)-NCAM, vimentin, Ki-67, and Sox2. Minority subpopulations of cells expressed doublecortin, beta-III tubulin, synapsin I, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) consistent with increased lineage restriction. A human microarray detected porcine transcripts for nogoA (RTN4) and stromal cell-derived factor 1 (SDF1), possibly cyclin D2 and Pbx1, but not CD133, Ki-67, nestin, or nucleostemin. Subsequent RT-PCR showed pig forebrain precursors to be positive for cyclin D2, nucleostemin, nogoA, Pbx1, vimentin, and a faint band for SDF1, whereas no signal was detected for CD133, fatty acid binding protein 7 (FABP7), or Ki-67. Human forebrain progenitor cells were positive for all the genes mentioned. This study shows that porcine neural precursors share many characteristics with their human counterparts and, thus, may be useful in porcine cell transplantation studies potentially leading to the application of this strategy in the setting of nervous system disease and injury.

Animals↗
PubMed1992

Cytoskeletal architecture of the matrix cell and neuroblast in the neural tube of the chick embryo.

Cytoskeletal architecture of the matrix cell and neuroblast in the wall of midbrain of 4-6 day-old chick embryos was examined by electron microscopy and immunohistochemistry. The matrix cell, the undifferentiated stem cell later producing neurons and glial cells in the central nervous system, is characterized ultrastructurally by abundant free ribosomes and a poorly developed cytomembrane system. A few microtubules running in random directions are observed in the matrix cell body. In the cell processes, microtubules are oriented longitudinally, and linked with each other by cross-bridges, presumably composed of microtubule-associated proteins (MAPs). The cell processes contain abundant cytoplasmic filaments including a large amount of actin filaments which adhere to the plasma membrane of junctional complexes located immediately below the inner surface of the neural tube. In the neuroblast which has been differentiated from the matrix cell, the cytomembranous organelles, especially rough endoplasmic reticulum are markedly better developed than in the matrix cell; microtubules are more numerous in the cell body. The cell process contains many microtubules with cross-bridges and a few intermediate filaments, which are relatively characteristic of the cytoskeleton of the neuroblast. Phalloidin-staining and immunohistochemistry showed that the neuroblast was richer in F-actin, beta-tubulin, MAP1, MAP2, tau, calspectin, and synapsin I than the matrix cell. As the matrix cell differentiates into the neuroblast, both the cytoskeletal and cytomembranous systems proved to develop features, characteristic of a neuron.

Animals↗
PubMed1999

CaM kinase II: a protein kinase with extraordinary talents germane to insulin exocytosis.

CaM kinase II, a multifunctional Ca2+/calmodulin-dependent protein kinase, is expressed in the pancreatic beta-cell and is activated by glucose and other secretagogues in a manner correlating with insulin secretion. It is proposed that the activation of CaM kinase II mediates some of the actions of Ca2+ on the exocytosis of insulin secretory granules. This suggestion is supported by the localization of CaM kinase II to the insulin secretory granule and by the identification of two secretory-relevant proteins, MAP-2 and synapsin I, as endogenous substrates in the beta-cell. Mechanistically, CaM kinase II appears to be involved in secretory steps proximal to granule fusion at the plasmalemma, and may facilitate protracted secretion through control of the interaction of granules with the cell cytoskeleton and their mobilization from intracellular synthesis sites. Through its unique regulatory properties, however, CaM kinase II is predicted to serve in more specialized aspects of the secretory process. In particular, the ability of CaM kinase II to remain active after cell stimulation is suggested to represent a mechanism by which releasable pools of granules are replenished between stimuli.

Animals↗
PubMed1988

Spectrin and related molecules.

This review begins with a complete discussion of the erythrocyte spectrin membrane skeleton. Particular attention is given to our current knowledge of the structure of the RBC spectrin molecule, its synthesis, assembly, and turnover, and its interactions with spectrin-binding proteins (ankyrin, protein 4.1, and actin). We then give a historical account of the discovery of nonerythroid spectrin. Since the chicken intestinal form of spectrin (TW260/240) and the brain form of spectrin (fodrin) are the best characterized of the nonerythroid spectrins, we compare these molecules to RBC spectrin. Studies establishing the existence of two brain spectrin isoforms are discussed, including a description of the location of these spectrin isoforms at the light- and electron-microscope level of resolution; a comparison of their structure and interactions with spectrin-binding proteins (ankyrin, actin, synapsin I, amelin, and calmodulin); a description of their expression during brain development; and hypotheses concerning their potential roles in axonal transport and synaptic transmission.

Animals↗
PubMed2006

The receptor tyrosine kinase Met and its ligand hepatocyte growth factor are clustered at excitatory synapses and can enhance clustering of synaptic proteins.

The receptor protein tyrosine kinase Met and its ligand, hepatocyte growth factor, regulate cellular morphology, intercellular adhesion, and interactions among junctional proteins in numerous cell types. However, they have not been extensively studied in the central nervous system. We report that Met is clustered at excitatory synapses and that treatment of neurons with hepatocyte growth factor can enhance expression and clustering of synaptic proteins. We demonstrate that Met is present in clusters that strongly colocalize with the NR2B subunit of the N-methyl-D-aspartate receptor, PSD-95 and synapsin at excitatory synapses of hippocampal neurons in vitro. We also show that Met is clustered at the postsynaptic density of excitatory synapses in the CA1 region of the hippocampus with the use of immuno-electron microscopy. Hepatocyte growth factor also forms clusters that partially colocalize with PSD-95. Treatment of cultured neurons with exogenous hepatocyte growth factor increased expression of the NR2B subunit of the N-methyl-D-aspartate receptor, calcium/calmodulin-dependent protein kinase II, and the GluR1 subunit of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor. The size and number of clusters of these proteins were also increased at sites along dendrites in response to hepatocyte growth factor. These results suggest a novel role for Met and hepatocyte growth factor in regulating synapses.

Animals↗
PubMed1999

Chronic ethanol upregulates NMDA and AMPA, but not kainate receptor subunit proteins in rat primary cortical cultures.

The present study examined the effects of chronic ethanol exposure on the expression of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxalone (AMPA) and kainate receptor subunit proteins in rat cortical neuronal cultures grown in media containing 2 mM (high) or 0.1 mM (low) glutamine. Immunoblot analysis of NMDA (NR1, NR2A, NR2B, and NR2D), AMPA (GluR1 and GluR2/3), and kainate (GluR6/7) subunit polypeptides in 3-, 5-, 8-, 10-, and 12 day-old-cultures showed that NMDA receptor subunits NR1, NR2A, and NR2B and AMPA receptor subunits GluR2/3 progressively increased as a function of time, whereas levels of NMDA subunit NR2D were high at day 3 and progressively declined to barely detectable levels by day 12. Levels of AMPA subunit GluR1 and the kainate subunit GluR6/7 remained stable throughout the time course. Replacing the culture media with low glutamine media at culture day 5 did not alter the levels of subunit proteins measured at culture days 9 and 13. However, exposure of low glutamine cultures to 100 mM ethanol for 4 days (starting at culture day 9) significantly increased the levels of NMDA receptor subunits (NR1, NR2A, and NR2B) and AMPA receptor subunits (GluR1 and GluR2/3), but had no effect upon kainate receptor subunits (GluR6/7) or the synapse-associated proteins synapsin I and PSD-95. In contrast, chronic ethanol did not alter the levels of any of these subunit proteins in cells grown in high glutamine. These data demonstrate that under certain experimental conditions, prolonged exposure to ethanol upregulates NMDA and AMPA receptor subunit proteins, but has no effect upon kainate receptor subunit proteins. Because we have previously shown that acute ethanol can inhibit NMDA and AMPA, but not kainate, receptor function in these cultures, the increase in subunit expression likely reflects an adaptive response to the inhibitory effects of ethanol and suggests that both NMDA and AMPA receptors may play an important role in adaptation of the CNS to chronic ethanol.

Animals↗
PubMedDate not supplied

Neuronal NT-3 is not required for synaptic transmission or long-term potentiation in area CA1 of the adult rat hippocampus.

Neurotrophic factors, including BDNF and NT-3, have been implicated in the regulation of synaptic transmission and plasticity. Previous attempts to analyze synaptic transmission and plasticity in mice lacking the NT-3 gene have been hampered by the early death of the NT-3 homozygous knockout animals. We have bypassed this problem by examining synaptic transmission in mice in which the NT-3 gene is deleted in neurons later in development, by crossing animals expressing the CRE recombinase driven by the synapsin I promoter to animals in which the NT-3 gene is floxed. We conducted blind field potential recordings at the Schaffer collateral-CA1 synapse in hippocampal slices from homozygous knockout and wild-type mice. We examined the following indices of synaptic transmission: (1) input-output relationship; (2) paired-pulse facilitation; (3) post-tetanic potentiation; and (4) long-term potentiation: induced by two different protocols: (a) two trains of 100-Hz stimulation and (b) theta burst stimulation. We found no difference between the knockout and wild-type mice in any of the above measurements. These results suggest that neuronal NT-3 does not play an essential role in normal synaptic transmission and some forms of plasticity in the mouse hippocampus.

Animals↗