Abstract
Little is known about factors to control critical period for developmental plasticity. In vitro model of critical period for activity-dependent plasticity would be expected to make a substantial contribution to elucidate this problem. Corticospinal synapses were reconstructed in vitro by co-culturing the sensorimotor cortex and spinal cord slices of P0 Wister rats. Recordings of field EPSPs along 100μm-interval lattice in the spinal gray matter evoked by the stimulation of deep cortical layer allowed evaluation of spatial distribution of synapse formation quantitatively. Corticospinal synapses are formed diffusely throughout the spinal gray matter, but later the synapses in the ventral side are eliminated. This synapse elimination was blocked by APV, suggesting that this process is NMDA-dependent. Using this in vitro system, we made a detailed quantitative analysis on the time course of the sensitivity to APV. By changing the application period of APV, we found that 6-11DIV application is necessary and sufficient for a full and irreversible block of synapse elimination. Application of a specific blocker of NR2B containing NMDA-R, ifenprodil (10μM) during the critical period blocked the synapse elimination. However, a blocker of NR2A containing NMDA-R, NVP-AAM077 (0.4μM) showed no effect. These suggest that NMDA-dependent corticospinal synapse elimination depends on NR2B containing NMDA-R. It is possible that there is a shift of glutamate receptor subtype from NR2B to 2A or NR2B-NMDA-R to AMPA-R. This shift may explain the end of the critical period. [Jpn J Physiol 55 Suppl:S144 (2005)]
