CHRONIC NMDA RECEPTOR ANTAGONISM DURING RETINOTOPIC MAP FORMATION DEPRESSES CAM KINASE-II DIFFERENTIATION IN RAT SUPERIOR COLLICULUS

We examined the effects of chronic NMDA receptor antagonism on the nor mal postnatal differentiation of calcium- and calmodulin-dependent kin ase II (CaM kinase II) in the rat superior colliculus, At postnatal da y (P) zero, most CaM kinase II protein, as well as CaM kinase II activ ity, was detected in the soluble fraction. In vitro phosphorylation of PO superior colliculus revealed several prominent substrates in both the particulate and soluble fractions. At P19 there was more particula te enzyme than soluble enzyme, and CaM kinase II activity in the parti culate fraction was higher than in PO particulate tissue. Additionally , in vitro phosphorylation of P19 superior colliculus revealed many mo re CaM kinase II substrates. Chronic NMDA receptor antagonism with 2-a mino-5-phosphonovalerate (DL-AP5) caused CaM kinase II to retain many of the characteristics of the enzyme found in PO untreated superior co lliculus. In P19 superior colliculus treated with DL-AP5 from birth, m ost of the protein was in the soluble fraction, CaM kinase II activity was largely restricted to the soluble fraction, and only a few substr ates were observed by in vitro phosphorylation. These effects were not observed in tissue treated with the inactive isomer, L-AP5. These res ults suggest that synaptic maturation is slowed by antagonism of NMDA receptors during retinotopic map formation.