HIPPOCAMPAL LONG-TERM POTENTIATION IS NORMAL IN HEME OXYGENASE-2 MUTANT MICE

We have generated mice deficient in HO-2, the major cerebral isoform o f heme oxygenase, in order to assess the potential role of carbon mono xide as a retrograde messenger in hippocampal LTP. Cerebral HO catalyt ic activity was markedly reduced in the HO-2 mutant mice, yet no diffe rences were found between wild types and mutants in gross neuroanatomi cal structure, in basal hippocampal synaptic transmission, or in the a mount of potentiation produced by various LTP induction protocols. Fur thermore, zinc protoporphyrin IX, an inhibitor of HO, had nearly ident ical inhibitory effects on LTP in wild-type and HO-2 mutant hippocampa l slices. Our data indicate that carbon monoxide produced endogenously by HO is unlikely to be a neuromodulator required for LTP in the hipp ocampus.