N-methyl-D-aspartate receptor independent changes in expression of polysialic acid-neural cell adhesion molecule despite blockade of homosynaptic long-term potentiation and heterosynaptic long-term depression in the awake freely behaving rat dentate gyrus.
Investigations examining the role of polysialic acid (PSA) on the neural cell adhesion molecule (NCAM) in synaptic plasticity have yielded inconsistent data. Here, we addressed this issue by determining whether homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) induce changes in the distribution of PSA-NCAM in the dentate gyrus (DG) of rats in vivo. In addition, we also examined whether the observed modifications were initiated via the activation of N-methyl-D-aspartate (NMDA) receptors. Immunocytochemical analysis showed an increase in PSA-NCAM positive cells both at 2 and 24 h following high-frequency stimulation of either medial or lateral perforant paths, leading to homosynaptic LTP and heterosynaptic LTD, respectively, in the medial molecular layer of the DG. Analysis of sub-cellular distribution of PSA-NCAM by electron microscopy showed decreased PSA dendritic labelling in LTD rats and a sub-cellular relocation towards the spines in LTP rats. Importantly, these modifications were found to be independent of the activation of NMDA receptors. Our findings suggest that strong activation of the granule cells up-regulates PSA-NCAM synthesis which then incorporates into activated synapses, representing NMDA-independent plastic processes that act synergistically on LTP/LTD mechanisms without participating in their expression.
Rodríguez
Jose J
JJ
Faculty of Life Sciences, The University of Manchester, Manchester, UK. Jose.Rodriguez-arellano@manchester.ac.uk
Dallérac
Glenn M
GM
Tabuchi
Masashi
M
Davies
Heather A
HA
Colyer
Frances M
FM
Stewart
Michael G
MG
Doyère
Valérie
V
D000818:Animals; D001703:Biophysics; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012794:Sialic Acids / Q000378:metabolism*; D013569:Synapses / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors; D014851:Wakefulness
D018691:Excitatory Amino Acid Antagonists; D039842:Neural Cell Adhesion Molecule L1; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid