LONG-TERM BUT NOT SHORT-TERM PLASTICITY AT MOSSY FIBER SYNAPSES IS IMPAIRED IN NEURAL CELL-ADHESION MOLECULE-DEFICIENT MICE

Cell adhesion molecules (CAMs) are known to be involved in a variety o f developmental processes that play key roles in the establishment of synaptic connectivity during embryonic development, but recent evidenc e implicates the same molecules in synaptic plasticity of the adult. I n the present study, we have used neural CAM (NCAM)-deficient mice, wh ich have learning and behavioral deficits, to evaluate NCAM function i n the hippocampal mossy fiber system. Morphological studies demonstrat ed that fasciculation and laminar growth of mossy fibers were strongly affected, leading to innervation of CA3 pyramidal cells at ectopic si tes, whereas individual mossy fiber boutons appeared normal. Electroph ysiological recordings performed in hippocampal slice preparations rev ealed that both basal synaptic transmission and two forms of short-ter m plasticity, i,e,, paired-pulse facilitation and frequency facilitati on, were normal in mice lacking all forms of NCAM, However, long-term potentiation of glutamatergic excitatory synapses after brief trains o f repetitive stimulation was abolished. Taken together, these results strongly suggest that in the hippocampal mossy fiber system, NCAM is e ssential both for correct axonal growth and synaptogenesis and for lon g term changes in synaptic strength.