INCREASE IN PROPORTION OF HIPPOCAMPAL SPINE SYNAPSES EXPRESSING NEURAL CELL-ADHESION MOLECULE NCAM180 FOLLOWING LONG-TERM POTENTIATION

Neural recognition molecules such as the neural cell adhesion molecule (NCAM) have been implicated in synaptic plasticity, including long-te rm potentiation (LTP), sensitization, and learning and memory, The maj or isoform of NCAM carrying the longest cytoplasmic domain of all NCAM isoforms (NCAM180) is predominantly localized in postsynaptic membran es and postsynaptic densities of hippocampal neurons, with only a prop ortion of synapses carrying detectable levels of NCAM180. To investiga te whether this differential expression of NCAM180 may correlate with distinct states of synaptic activity, LTP was induced by high-frequenc y stimulation of the perforant path and the percentage of NCAM180 immu nopositive spine synapses determined in the outer third of the dentate molecular layer of the dentate gyrus by immunoelectron microscopy, Tw enty-four hours following induction of LTP by high-frequency stimulati on, the percentage of spine synapses expressing NCAM180 increases from 37% (passive control) to 70%. This increase was inhibited by the nonc ompetitive N-methyl-D-aspartate receptor antagonist MK801. Following r epeated LTP induction at 10 consecutive days with one tetanization eac h day, 60% of all spine synapses were NCAM180 immunoreactive. Compared to passive control animals, the percentage of NCAM180 expressing syna pses in low-frequency stimulated animals decreased from 37% to 28%, Sp ine synapses in the inner part of the dentate molecular layer not cont acted by the afferents of the perforant path did not change the percen tage of NCAM180-expressing synapses, The results obtained by the poste mbedding immunogold staining technique confirmed the difference in NCA M180 expression of spine synapses between passive control and potentia ted animals. These observations suggest a role for NCAM180 in synaptic remodeling accompanying LTP, (C) 1998 John Wiley & Sons, Inc.