THE IMPAIRED LONG-TERM POTENTIATION IN THE CA1 FIELD OF THE HIPPOCAMPUS OF COGNITIVE DEFICIENT MICROENCEPHALIC RATS IS RESTORED BY D-SERINE

Rat embryos exposed on gestational day 15 to methyl-azoxymethanol acet ate develop a microencephaly characterized primarily by a hypoplasia o f the neocortex and CA fields of the hippocampus that in adulthood is associated with disturbances in learning. In brain slices prepared fro m microencephalic rats, we have examined the field excitatory postsyna ptic potentials and population spike in the CA1 field of the hippocamp us evoked by stimulation of the stratum radiatum. These parameters did not differ from those obtained in slices from control rats. High freq uency stimulation of the stratum radiatum afferent fibres, which readi ly induced long-term potentiation of the field excitatory postsynaptic potentials and population spike in the CA1 field of the hippocampus o f control rats, failed to induce long-term potentiation in that of mic roencephalic rats. High frequency stimulation of the perforant path re adily elicited long-term potentiation in the dentate gyrus of both con trol and microencephalic rats. Picrotoxin had no apparent effect on fi eld excitatory postsynaptic potentials and population spike in the CA1 field of the microencephalic rats, indicating that little GABAergic i nhibition was present in slices from these rats. D-2-Amino-phosphonova lerate suppressed the field potentials in slices from microencephalic rats by more than 50%, suggesting that N-methyl-D-aspartate receptors contributed markedly to the synaptic responses evoked by single stimul i. D-Serine, but not picrotoxin, restored long-term potentiation in th e CA1 field of the microencephalic rats. The D-serine effect was preve nted by pretreating the slices with either 7-chloro-kynurenate or D-2- amino-phosphonovalerate. The failure to induce long-term potentiation, if also found in vivo, may be among the factors related to the learni ng deficits displayed by these rats.