We have generated mice deficient in HO-2, the major cerebral isoform of heme oxygenase, in order to assess the potential role of carbon monoxide as a retrograde messenger in hippocampal LTP. Cerebral HO catalytic activity was markedly reduced in the HO-2 mutant mice, yet no differences were found between wild types and mutants in gross neuroanatomical structure, in basal hippocampal synaptic transmission, or in the amount of potentiation produced by various LTP induction protocols. Furthermore, zinc protoporphyrin IX, an inhibitor of HO, had nearly identical inhibitory effects on LTP in wild-type and HO-2 mutant hippocampal slices. Our data indicate that carbon monoxide produced endogenously by HO is unlikely to be a neuromodulator required for LTP in the hippocampus.
Bibliographical noteFunding Information:
We are grateful to Dr. T. Dawson for help with neuroanatomical analysis and for valuable discussions. We thank Dr. S. Snyder for discussions and for allowing work to be done in his laboratory, and Dr. Y. Wang for comments on the manuscript. T. J. O. was supported by a grant from the Esther A. and Joseph Klingenstein Fund. S. T. was supported by grants from the Howard Hughes Medical Institute, the Shionogi Institute for Medical Science, and the National Institutes of Health (RO1-NS32925-02). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.