Insulin promotes functional induction of silent synapses in differentiating rat neocortical neurons

Long-term synaptic plasticity is thought to underlie synaptic reorganizatio n phenomena that occur during neocortical development. Recently, it has bee n proposed, that the functional induction of AMPA receptors at silent gluta matergic synapses is of major importance in activity-dependent, development al plasticity. To investigate the mechanisms involved in the developmental regulation of silent synapses, we analysed the functional maturation of the thalamocortical projection in culture. A large proportion of the thalamoco rtical synapses were functionally silent at an early stage in vitro. During further differentiation, the incidence of silent synapses decreased drasti cally, indicating a conversion of silent into functional synapses. Chronic blockade of spontaneous network activity by addition of tetrodotoxin to the culture medium strongly impaired this developmental maturation. Moreover, the developmental decline in the proportion of silent synapses was dramatic ally accelerated by chronic addition of the neurotrophic factor, insulin. T his effect of insulin was partly dependent on spontaneous activity. Thus, i nsulin appears to be involved in the modulation of long-term developmental plasticity at immature glutamatergic synapses.