Key points are not available for this paper at this time.
Polysialic acid (PSA) is a post-translational protein modification that is widely expressed among neural cell types during development. Found predominantly on the neural cell adhesion molecule (NCAM), PSA becomes restricted to regions of neurogenesis and neuroplasticity in the adult. In the mammalian genome, two polysialyltransferases termed ST8Sia-II and ST8Sia-IV have been hypothesized to be responsible for the production of PSA in vivo. Approaches to discover PSA function have involved the application of endoneuraminidase-N to remove PSA and genetic manipulations in the mouse to deplete either NCAM or ST8Sia-IV. Here we report the production and characterization of mice deficient in the ST8Sia-II polysialyltransferase. We observed alterations in brain PSA expression unlike those observed in mice lacking ST8Sia-IV. This included a PSA deficit in regions of neurogenesis but without changes in the frequency of mitotic neural progenitor cells. In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not impair hippocampal synaptic plasticity but instead resulted in the misguidance of infrapyramidal mossy fibers and the formation of ectopic synapses in the hippocampus. Consistent with studies of animal models bearing these morphological changes, ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced behavioral responses to Pavlovian fear conditioning. PSA produced by the ST8Sia-II polysialyltransferase modifies memory and behavior processes that are distinct from the neural roles reported for ST8Sia-IV. This genetic partitioning of PSA formation engenders discrete neurological processes and reveals that this post-translational modification forms the predominant basis for the multiple functions attributed to the NCAM glycoprotein. Polysialic acid (PSA) is a post-translational protein modification that is widely expressed among neural cell types during development. Found predominantly on the neural cell adhesion molecule (NCAM), PSA becomes restricted to regions of neurogenesis and neuroplasticity in the adult. In the mammalian genome, two polysialyltransferases termed ST8Sia-II and ST8Sia-IV have been hypothesized to be responsible for the production of PSA in vivo. Approaches to discover PSA function have involved the application of endoneuraminidase-N to remove PSA and genetic manipulations in the mouse to deplete either NCAM or ST8Sia-IV. Here we report the production and characterization of mice deficient in the ST8Sia-II polysialyltransferase. We observed alterations in brain PSA expression unlike those observed in mice lacking ST8Sia-IV. This included a PSA deficit in regions of neurogenesis but without changes in the frequency of mitotic neural progenitor cells. In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not impair hippocampal synaptic plasticity but instead resulted in the misguidance of infrapyramidal mossy fibers and the formation of ectopic synapses in the hippocampus. Consistent with studies of animal models bearing these morphological changes, ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced behavioral responses to Pavlovian fear conditioning. PSA produced by the ST8Sia-II polysialyltransferase modifies memory and behavior processes that are distinct from the neural roles reported for ST8Sia-IV. This genetic partitioning of PSA formation engenders discrete neurological processes and reveals that this post-translational modification forms the predominant basis for the multiple functions attributed to the NCAM glycoprotein. Polysialic acid (PSA) 1The abbreviations used are: PSA, polysialic acid; NCAM, the neural cell adhesion molecule; endo-N, endoneuraminidase; LTP, long term potentiation; LTD, long term depression; ES, embryonic stem; RT, reverse transcriptase; BrdUrd, 5-bromo-2′-deoxyuridine; ACSF, artificial cerebrospinal fluid; fEPSPs, field excitatory postsynaptic potentials; TBS, θ-burst stimulation; STP, short term potentiation; HFS, high frequency stimulation; PTP, post-tetanic potentiation; CS, conditioned stimulus; ANOVA, analysis of variance; NMDA, N-methyl-d-aspartic acid; BDA, biotinylated dextran amine; wt, wild type. is a post-translational modification consisting of a homopolymer of α2-8-linked sialic acids that participates in neural development (1Schachner M. Martini R. Trends Neurosci. 1995; 18: 183-191Google Scholar, 2Rutishauser U. Landmesser L. Trends Neurosci. 1996; 19: 422-427Google Scholar, 3Kiss J.Z. Troncoso E. Djebbara Z. Vutskits L. Muller D. Brain Res. Rev. 2001; 36: 175-184Google Scholar). Typically attached to N-glycans, PSA is produced in the Golgi apparatus and is found among a limited number of glycoproteins and predominantly on the neural cell adhesion molecule (NCAM). Enzymatic removal of PSA by using endoneuraminidase (endo-N) induces various neurological abnormalities including deficits in hippocampal long term potentiation (LTP) and long term depression (LTD), spatial learning, cell migration, and axonal targeting as observed in NCAM-deficient mice (4Tomasiewicz H. Ono K. Yee D. Thompson C. Goridis C. Rutishauser U. Magnuson T. Neuron. 1993; 11: 1163-1174Google Scholar, 5Cremer H. Lange R. Christoph A. Plomann M. Vopper G. Roes J. Brown R. Baldwin S. Kraemer P. Scheff S. Barthels D. Rajewsky K. Wille W. Nature. 1994; 367: 455-459Google Scholar, 6Muller D. Wang C. Skibo G. Toni N. Cremer H. Calaora V. Rougon G. Kiss J.Z. Neuron. 1996; 17: 413-422Google Scholar, 7Becker C.G. Artola A. Gerardy-Schahn R. Becker T. Welzl H. Schachner M. J. Neurosci. Res. 1996; 45: 143-152Google Scholar, 8Hu H. Tomasiewicz H. Magnuson T. Rutishauser U. Neuron. 1996; 16: 735-743Google Scholar, 9Cremer H. Chazal G. Goridis C. Represa A. Mol. Cell. Neurosci. 1997; 8: 323-335Google Scholar, 10Seki T. Rutishauser U. J. Neurosci. 1998; 18: 3757-3766Google Scholar, 11Cremer H. Chazal G. Carleton A. Goridis C. Vincent J.D. Lledo P.M. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 13242-13247Google Scholar, 12Cremer H. Chazal G. Lledo P.M. Rougon G. Montaron M.F. Mayo W. Le Moal M. Abrous D.N. Int. J. Dev. Neurosci. 2000; 18: 213-220Google Scholar, 13Bruses J.L. Rutishauser U. Biochimie (Paris). 2001; 83: 635-643Google Scholar). PSA may alter the adhesive property of NCAM in mediating these processes and may also influence cell-cell communication involving integrins, cadherins, and members of the immunoglobulin superfamily (14Rutishauser U. J. Cell. Biochem. 1998; 70: 304-312Google Scholar, 15Fujimoto I. Bruses J.L. Rutishauser U. J. Biol. Chem. 2001; 276: 31745-31751Google Scholar). Expression of PSA is high in embryonic brain and generally reduced in the adult. However, PSA is continuously present in some adult regions such as the olfactory bulb, hippocampus, and hypothalamus, coincident to where neurogenesis and neuronal plasticity persist (16Seki T. Arai Y. Neurosci. Res. 1993; 17: 265-290Google Scholar, 17Kuhn H.G. Dickinson-Anson H. Gage F.H. J. Neurosci. 1996; 16: 2027-2033Google Scholar). Two genes encoding polysialyltransferases ST8Sia-II (STX) and ST8Sia-IV (PST) are independently capable of directing PSA synthesis in vitro (18Eckhardt M. Mühlenhoff M. Bethe A. Koopman J. Frosch M. Gerardy-Schahn R. Nature. 1995; 373: 715-718Google Scholar, 19Kojima N. Yoshida Y. Tsuji S. FEBS Lett. 1995; 373: 119-122Google Scholar, 20Nakayama J. Fukuda M.N. Fredette B. Ranscht B. Fukuda M. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 7031-7035Google Scholar, 21Scheidegger E.P. Sternberg L.R. Roth J. Lowe J.B. J. Biol. Chem. 1995; 270: 22685-22688Google Scholar, 22Angata K. Fukuda M. Biochimie (Paris). 2003; 85: 195-206Google Scholar). Although ST8Sia-II and -IV share 59% amino acid identity, they are expressed in different spatial and temporal patterns among neural tissues (23Yoshida Y. Kurosawa N. Kanematsu T. Kojima N. Tsuji S. J. Biol. Chem. 1996; 271: 30167-30173Google Scholar, 24Kurosawa N. Yoshida Y. Kojima N. Tsuji S. J. Neurochem. 1997; 69: 494-503Google Scholar, 25Hildebrandt H. Becker C. Murau M. Gerardy-Schahn R. Rahmann H. J. Neurochem. 1998; 71: 2339-2348Google Scholar, 26Ong E. Nakayama J. Angata K. Reyes L. Katsuyama T. Arai Y. Fukuda M. Glycobiology. 1998; 8: 415-424Google Scholar, 27Eckhardt M. Gerardy-Schahn R. Glycobiology. 1998; 8: 1165-1172Google Scholar, 28Takashima S. Yoshida Y. Kanematsu T. Kojima N. Tsuji S. J. Biol. Chem. 1998; 273: 7675-7683Google Scholar). To understand how the mammalian neurological system may be modulated in vivo by altered PSA formation, the genetic bases of PSA formation in vivo must be defined. To date this has been explored by analyzing mice lacking the ST8Sia-IV polysialyltransferase. NCAM expression was unaltered by ST8Sia-IV deficiency, whereas specific brain regions exhibited decreased PSA levels, and adult animals bore a restricted phenotype involving an impairment of LTD and LTP in the hippocampal CA1 region (29Eckhardt M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar). However, unlike NCAM deficiency, no decrease in LTP was and hippocampal mossy Here we report the and characterization of ST8Sia-II-deficient mice to the of this polysialyltransferase in neurological and the that PSA formation and NCAM ST8Sia-II ST8Sia-II was from a and used to a targeting was by two as J.D. J. 1996; Scholar). embryonic by and by bearing the ST8Sia-II expression of to ST8Sia-II the mouse for to phenotype was using and by and as E. Nakayama J. Angata K. Reyes L. Katsuyama T. Arai Y. Fukuda M. Glycobiology. 1998; 8: 415-424Google Scholar). used are as and tissues and with was by and with B. J. Biol. Chem. for to with in and with either mouse in or by or and by in and was by ST8Sia-II-deficient and mice an the the mice with and with and in to or was and in the of the hippocampus, for by and To of embryonic neural in was mice embryonic that with from mice and mice and as mice with of by in in the of the was as H. Chazal G. Goridis C. Represa A. Mol. Cell. Neurosci. 1997; 8: 323-335Google Scholar). or was as T. Rutishauser U. J. Neurosci. 1998; 18: 3757-3766Google Scholar, 26Ong E. Nakayama J. Angata K. Reyes L. Katsuyama T. Arai Y. Fukuda M. Glycobiology. 1998; 8: 415-424Google Scholar, M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar). To with for or with to with and with in from to ST8Sia-II-deficient mice and used for and removal of the the with a in in artificial cerebrospinal and in a with ACSF, instead of for the of from A. B. J. Scholar). In the continuously with in the the as for in the CA1 region but with some mice with ACSF, and to Z. Brown 1993; Scholar). of with and was using of from the of the CA1 region in to of by an from the in the of the CA1 and with with a of synaptic was LTP in the CA1 region was by θ-burst to and in the of of of was and to LTP (29Eckhardt M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar). was in the of to with an of of the of was as potentiation STP, short term was as a in the during LTP of LTP as in the of and with with and a of with of was to the of the cell was in the of the mossy responses for of with a and of of and frequency responses no of such as with multiple or of high frequency of of for or with an of To LTP in mossy are to LTP in an the was and during mossy responses of and no changes in the of responses of To that the by the of mossy fibers and not by the an of is to synaptic in mossy synapses 1995; was the of in responses reduced by for synaptic was of was as potentiation was as the in the of of LTP as in the of and by using an and in are reported as was used to using the and was in mice of by biotinylated dextran the the mouse was with and in was by using and the in from G. Brain in Scholar). animals to and to as and using and of mice of and ST8Sia-II-deficient in a behavioral from that used by R. 2001; and as P. E. A. J. Neurosci. Scholar). This included such as and of and that mice in such a influence behavior in and that multiple the of a a of mice was also In the field was in a in an of using a apparatus and and analysis involved a apparatus mouse was in the the animal the a and a of was the of the for the mouse did not the was from the In the the for the mice to the was was used of in a was used for and analysis conditioned was an and the was a during the of the in the for and was as the of and the of high with with and during the was also mouse was to the and responses for to present a different and the mice in this behavior was for and during was to a a during mice from for in a in a that was in a different the used in the was the from the to the was the for to the was of on the This with and a without the mice to the spatial used in the This for mice with deficits and behavioral on the of mice this in from a a was with the of was the of the and a system was used to mouse and during and mouse was a in two of for animal was a the the was and was the mice to a was a attached to a that was the of the the was in of the in of and the to the was for termed including of produced of and in in and of and and two and as with the of and to the during function was by of the of the in a the mouse to a of with was also animal was was by a system that in to and changes in and mice in a and on the and the was to to the and the for for to of on the was reported and by the ST8Sia-II in the ST8Sia-II is among and multiple that the E.P. Sternberg L.R. Roth J. Lowe J.B. J. Biol. Chem. 1995; 270: 22685-22688Google Scholar). a of the a that is for J. Biol. Chem. 1995; 270: Scholar). encoding of the ST8Sia-II was for from the mouse that bore the to was the and the for the ST8Sia-II produced by to in or brain the that expression of ST8Sia-II in of ST8Sia-II of of was by and that the of ST8Sia-II lacking was produced in and the ST8Sia-II mice ST8Sia-II was and found to polysialyltransferase not by various further that the of ST8Sia-II not the of ST8Sia-IV PSA Expression and expression was reduced in the olfactory and of adult ST8Sia-II-deficient mice was no of PSA among the hypothalamus, hippocampus, and in contrast to the of PSA found among mice lacking ST8Sia-IV (29Eckhardt M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar). However, of the of ST8Sia-II-deficient mice a PSA deficit in the in the and progenitor that the cell high of is also an of neuronal and PSA expression with regions neurogenesis in the adult including the PSA in the reduced and in ST8Sia-II-deficient mice and In the was no in PSA expression in the PSA expression was reduced among neural the acid in the and of and ST8Sia-II-deficient of from mice and ST8Sia-II-deficient with neural are not in the of ST8Sia-II PSA expression in the of and brain are by and and are of regions in and as of are in the region of the in and However, high of PSA in the region of the with wild ST8Sia-II also in neural with PSA expression in the of the in To mitotic in embryonic and adult was a mouse embryonic and and adult mice and by and with number of in the adult of ST8Sia-II-deficient mice was not different from that of mice cell of PSA formation in the of neurogenesis was further by of neural embryonic these are in the as as the cell and patterns in the and the cell not and ST8Sia-II-deficient number of in the adult of ST8Sia-II-deficient mice was not different from that of mice that ST8Sia-II not the frequency of mitotic neuronal and of brain of the olfactory and among ST8Sia-II-deficient However, hippocampal infrapyramidal mossy was mossy fibers from in the and to the hippocampal to a that forms synapses in the of In fibers from the a infrapyramidal mossy the the cell and infrapyramidal mossy is the mossy and or with the to H. Chazal G. Goridis C. Represa A. Mol. Cell. Neurosci. 1997; 8: 323-335Google Scholar, 10Seki T. Rutishauser U. J. Neurosci. 1998; 18: 3757-3766Google Scholar, Brain Res. Scholar). ST8Sia-II-deficient the infrapyramidal mossy fibers to the region from adult further mossy fibers in ST8Sia-II cell in the and a these two mossy protein is a of in the as as and mossy fibers in the L. I. T. E. J. 1993; Scholar). and NCAM expression among the infrapyramidal mossy fibers in ST8Sia-II-deficient mice with the that these function mossy fibers to PSA in ST8Sia-II-deficient PSA expression was present on infrapyramidal mossy fibers to of these infrapyramidal mossy fibers was with the of ectopic synapses in where the in This is with the that mossy fibers and T. Rutishauser U. J. Neurosci. 1998; 18: 3757-3766Google Scholar). such synapses are in the of mice infrapyramidal mossy fibers not this hippocampal region in fibers the of the cell also observed in with ectopic synapses in ST8Sia-II-deficient mice ectopic synapses are also NCAM, and are among those fibers in and and of infrapyramidal mossy in ST8Sia-II was not to a in PSA expression on mossy fibers or changes in the or spatial of and in the region not widely of LTP in the CA1 region of the hippocampus, has been reported to be in NCAM and ST8Sia-IV deficient mice D. Wang C. Skibo G. Toni N. Cremer H. Calaora V. Rougon G. Kiss J.Z. Neuron. 1996; 17: 413-422Google Scholar, M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar). removal of PSA from hippocampal of mice by LTP and LTD D. Wang C. Skibo G. Toni N. Cremer H. Calaora V. Rougon G. Kiss J.Z. Neuron. 1996; 17: 413-422Google Scholar, 7Becker C.G. Artola A. Gerardy-Schahn R. Becker T. Welzl H. Schachner M. J. Neurosci. Res. 1996; 45: 143-152Google Scholar). In of produced and LTP in from animals of as potentiation during was and the of LTP was of number of mice of and LTP in ST8Sia-II-deficient mice and not different from for by of and the of responses of the not different ST8Sia-II-deficient mice and of excitatory not LTP mossy synapses with cell has been reported to be in NCAM-deficient mice H. Chazal G. Carleton A. Goridis C. Vincent J.D. Lledo P.M. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 13242-13247Google Scholar). synapses are for hippocampal and memory formation Neuron. Scholar, G. 2000; Scholar). LTP has distinct from CA1 LTP, of postsynaptic but by an in and of and protein 1994; Scholar). in by mossy using a number of and for mossy responses as frequency to in and ST8Sia-II-deficient of reduced the of in by did not the of in either or ST8Sia-II-deficient of high frequency HFS, in the of and LTP in from mice and of and LTP in ST8Sia-II-deficient mice and This was not different from among of LTP those observed in studies (29Eckhardt M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar, B. Bukalo O. A. U. Dityatev A. Schachner M. J. Neurosci. and by G. K. 1998; Scholar, M.F. A. D. Neurosci. Scholar). by a was in and in ST8Sia-II-deficient of LTP in and ST8Sia-II-deficient mice and not LTP in mossy synapses was not by ST8Sia-II and of ST8Sia-II mice in and of and In with that LTP in hippocampal regions CA1 and ST8Sia-II-deficient mice not in spatial using the However, and in exploratory and of and to of to in to in a field and in a ST8Sia-II-deficient mice in the field and in the of the the in the to the a of in the of exploratory behavior in the termed was among ST8Sia-II-deficient alterations from ST8Sia-II of behavior in a In the the ST8Sia-II-deficient mice also to to the in and that the animals be to ST8Sia-II-deficient mice they in these without in fear We and multiple and in a ST8Sia-II-deficient mice to and of and of and responses to also in ST8Sia-II-deficient mice of a a with an is and neural in the but not the hippocampus. In and the with the is and neural in and Neuron. Scholar). ST8Sia-II-deficient mice in the and of the as ST8Sia-II-deficient mice did not in the that the deficit in fear to was not to an to or to the ST8Sia-II polysialyltransferase to PSA formation in vivo and participates in distinct neurological processes that hippocampal axonal exploratory and responses to fear conditioning. PSA expression in some regions of neurogenesis was found to mitotic neuronal cell ST8Sia-II resulted in an of axonal targeting involving hippocampal infrapyramidal mossy fibers in with ectopic synapses where these fibers different by ST8Sia-II and ST8Sia-IV in PSA formation and discrete neurological functions that be attributed to these two ST8Sia-II and PSA in and of infrapyramidal mossy targeting have been with and fear G. 2000; Scholar, H. Brain Res. Scholar). In the field mouse with and infrapyramidal mossy to a and have reduced fear behavior Brain Res. 2001; Scholar). mice bearing a a of in have a in mossy and reduced to conditioned fear in and P. E. A. J. Neurosci. Scholar). behavioral changes are in mice that also have and infrapyramidal mossy M. Schachner M. D. Mol. Cell. Biol. Scholar). the infrapyramidal mossy fibers with reduced and high whereas with infrapyramidal mossy fibers and H. H. G. Brain Res. 1997; Scholar). is also involved in fear behavior and PSA Rev. Neurosci. 2000; Scholar, S. Rev. Neurosci. 2001; Scholar, J. E. Scholar). We PSA expression in the hypothalamus, and of adult ST8Sia-II-deficient and with the a in the not with a with the but not the hippocampus. However, fear the with the and Rev. Neurosci. 2000; Scholar, S. Rev. Neurosci. 2001; Scholar, 2001; 11: Scholar). multiple the brain including the and M. C. J.L. Brain Res. Scholar). ST8Sia-II fear responses by the and and have been in and to the and involving processes in the T. R. Trends Neurosci. 2001; Scholar, 2003; Scholar). the for the to mossy H. A. A. E. M. Neuron. 2001; Scholar, A. H. A. M. Cell. 2003; Scholar). is not PSA is to of the a with this has been of PSA and NCAM the characterization of mice deficient in or NCAM, we the of to PSA expression and neurological functions ST8Sia-II and ST8Sia-IV in PSA formation is in some brain However, in the PSA in the of either ST8Sia-II or ST8Sia-IV that in some polysialyltransferases forms of hippocampal synaptic LTP and LTD in the hippocampal CA1 region are PSA, and PSA produced by ST8Sia-IV. LTP a function of the NCAM protein of PSA of polysialic acid and NCAM function in neural development and synaptic of of neural NCAM in and NCAM in in adult NCAM of mossy and NCAM In in adult in a NCAM to multiple neurological abnormalities (4Tomasiewicz H. Ono K. Yee D. Thompson C. Goridis C. Rutishauser U. Magnuson T. Neuron. 1993; 11: 1163-1174Google Scholar, 5Cremer H. Lange R. Christoph A. Plomann M. Vopper G. Roes J. Brown R. Baldwin S. Kraemer P. Scheff S. Barthels D. Rajewsky K. Wille W. Nature. 1994; 367: 455-459Google Scholar, 6Muller D. Wang C. Skibo G. Toni N. Cremer H. Calaora V. Rougon G. Kiss J.Z. Neuron. 1996; 17: 413-422Google Scholar, 7Becker C.G. Artola A. Gerardy-Schahn R. Becker T. Welzl H. Schachner M. J. Neurosci. Res. 1996; 45: 143-152Google Scholar, 8Hu H. Tomasiewicz H. Magnuson T. Rutishauser U. Neuron. 1996; 16: 735-743Google Scholar, 9Cremer H. Chazal G. Goridis C. Represa A. Mol. Cell. Neurosci. 1997; 8: 323-335Google Scholar, 10Seki T. Rutishauser U. J. Neurosci. 1998; 18: 3757-3766Google Scholar, 11Cremer H. Chazal G. Carleton A. Goridis C. Vincent J.D. Lledo P.M. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 13242-13247Google Scholar). We that the of observed are present in mice with either ST8Sia-II or ST8Sia-IV mice exhibited a in infrapyramidal mossy axonal targeting T. Rutishauser U. J. Neurosci. 1998; 18: 3757-3766Google Scholar, O. Welzl H. D. T. N. S. D. H. K. Schachner M. J. Neurosci. 2000; Scholar). This was not observed among mice (29Eckhardt M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google that targeting of infrapyramidal mossy a function of PSA that is NCAM and NCAM also LTP in of the CA1 a function involving ST8Sia-IV D. Wang C. Skibo G. Toni N. Cremer H. Calaora V. Rougon G. Kiss J.Z. Neuron. 1996; 17: 413-422Google Scholar, M. Bukalo O. Chazal G. Wang L. Goridis C. Schachner M. Gerardy-Schahn R. Cremer H. Dityatev A. J. Neurosci. 2000; 20: 5234-5244Google Scholar). However, NCAM-deficient as as mice with to remove PSA, have a and a olfactory bulb, to of H. Tomasiewicz H. Magnuson T. Rutishauser U. Neuron. 1996; 16: 735-743Google whereas mice lacking either ST8Sia-II or ST8Sia-IV have a and olfactory This involving the two an polysialyltransferase may among these cells. and mice deficient in ST8Sia-II and ST8Sia-IV this Although of PSA formation and function in vivo is the basis for the observed in PSA studies of ST8Sia-II the of in PSA in of this a in among mossy fibers and cells. We also the that PSA on infrapyramidal mossy fibers to with mossy fibers in the hippocampus. In ST8Sia-II are expressed in this region K. Nakayama J. Fredette B. K. Ranscht B. Fukuda M. J. Biol. Chem. 1997; Scholar). reduced of PSA on in ST8Sia-II-deficient mice may the of infrapyramidal mossy fibers to and plasticity by PSA may also be by the of and in adult M. Rutishauser U. M. 2001; Scholar). In the adult hippocampus, as as with hippocampal PSA and NCAM expression with changes in neural plasticity involving mossy and Montaron M.F. C. M. S. Rougon G. Le Moal M. Abrous D.N. J. Neurosci. 1998; Scholar, C. K. C. 2001; Scholar, C. Biol. 2003; Scholar). ST8Sia-II polysialyltransferase to exploratory and fear that are by in contrast to the neurological processes by ST8Sia-IV that in these that PSA is a post-translational modification by multiple that discrete functions in vivo and the basis for the of the neurological roles attributed to the NCAM glycoprotein. We M. for of mice bearing the ST8Sia-II and and Ranscht for We the for of of for to and behavioral
Angata et al. (Thu,) studied this question.