SUPPRESSION OF SYNAPSIN-II INHIBITS THE FORMATION AND MAINTENANCE OF SYNAPSES IN HIPPOCAMPAL CULTURE

Numerous synaptic proteins, including several integral membrane protei ns, have been assigned roles in synaptic vesicle fusion with or retrie val from the presynaptic plasma membrane. In contrast, the synapsins, neuron-specific phosphoproteins associated with the cytoplasmic surfac e of synaptic vesicles, appear to play a much broader role, being invo lved in the regulation of neurotransmitter release and in the organiza tion of the nerve terminal, Here we have administered antisense synaps in II oligonucleotides to dissociated hippocampal neurons, either befo re the onset of synaptogenesis or 1 week after the onset of synaptogen esis, In both cases, synapsin II was no longer detectable within 24-48 h of treatment, After 5 days of treatment, cultures were analyzed for the presence of synapses by synapsin I and synaptophysin antibody lab eling and by electron microscopy, Cultures in which synapsin II was su ppressed after axon elongation, but before synapse formation, did not develop synapses, Cultures in which synapsin II was suppressed after t he development of synapses lost most of their synapses. Remarkably, wi th the removal of the antisense oligonucleotides, neurons and their sy naptic connections recovered, These studies lead us to conclude that s ynapsin II is involved in the formation and maintenance of synapses in hippocampal neurons.