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

Abstract

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 j. j. rodri 'guez 1,2 * , g. m. dalle ' rac 3 * , m. tabuchi 1 , h. a. davies 4 , f. m. colyer 4 , m. g. stewart 4 and v. doye ' re 3 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.

Sacral nerve stimulation increases activation of the primary somatosensory cortex by anal canal stimulation in an experimental model

“…They suggested that this rapid response resulted from release from large dense‐core vesicles rich in PSA‐NCAM. An alternative explanation can be found in the work of Rodríguez and co‐workers41, who reported a rapid increase (within 10 min) of mRNA levels encoding the sialyltransferase enzymes in rat dentate gyrus following LTP induction.…”

The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

“…Previous studies have shown PSA-NCAM is essential in the activity-dependent induction of hippocampal LTP and LTD [35], where the polysialylation of NCAM is positively correlated with neural activity of glutamatergic neurons [120, 121]. Moreover, inhibiting the polysialylation of NCAM reduces the rate of dendritic spine formation and decreases the stability of these spines [122].…”

Frizzled-5, a receptor for the synaptic organizer Wnt7a, regulates activity-mediated synaptogenesis

“…To further investigate the role of neuronal activity on Fz5 localization, we examined the effect of patterned electrical stimulation, shown to regulate the distribution of a number of receptors (Du et al, 2000;Hayashi et al, 2000;Rodriguez et al, 2008;Shi et al, 1999). We used two different electrical stimuli to induce neuronal activity.…”