Dear Dr. ****:

Thank you for your letter dated September 16, 1992. Enclosed please find a 3.5-inch floppy disk and 3 copies of revised version of the paper; "Title (MS #J***-2)." by autors. The 3.5 inch floppy disk was formatted by Apple Macintosh computer, and the application used was Microsoft Word ver. 4.00B.

We believe that the paper has been much improved, Iargely as a result of the referee's many thoughtful comments. I would like to explain below how we have responded to each comment.

ANSWERS TO REFREE'S COMMENTS

TO REVIEWER #1 :

Thank you for your kind comments. We checked references and corrected some of them. Then, English style was also corrected throughout the paper.

TO REVIEWER #2:

1. One must therefore ask for more critical discussion . . . .

We thought that present 5-HT responses were not raised from the artifacts by experimental conditions (i.e. the enzymatic treatments). By using dissociated neurons, we already analyzed many neurotransmitter-induced responses (i.e. glycine, GABA, NMDA) and voltage-operated channels (*** and ***, J. Neurophysiol. 62,1400-1409,1989; *** et al., Am. J. Physiol. 256, C1153-C1159,1989; **** et al., J. Physiol. 412, 181-195, 1989; *** et al., J. Physiol. 447, 309-327, 1992; *** et al., J. Neurophysiol. 66, 497-504, 1991, *** et al., Neurosci Res. 8, 114-123, 1990). Based on these results, we successfully explained previous phenomena in brain slices using microelectrode technique. A more critical discussion of the present experimental conditions can be find in the previous paper (*** et al., Neuroreport, 1992). Please refer to the enclosed reprint of the paper.

Yakel did failed to see our present response in cultured mouse embryonic hippocampal neurons. We thought that the characters of cells were changed with the process in culture conditions. It is, therefore, not surprizing that the 5-HT responses of acutely dissociated neurons were different from those of the cultured neurons. On this point, we added further discussion in p.15, Iines 7-13.

2. The concem is amplified by the fact that. . . .

Indeed, some papers suggest that 5-HT2-induced responses were mediated by intracellular cAMP (e.g. Yakel et al., J. Neurosci. 8, 1273-1285, 1988). However, many lines of evidence suggest that 5-HTI family receptors were coupled to adenylate cyclase and 5-HT2 family receptor was to PLC via G-proteins (Reviews in Peroutka, TIPS, 496-500, 1988 and Hartig, TIPS, 64-69, 1989). We cited the biochemical studies mentioned 5-HT2 responses coupled to PLC and discussed about it in p. 16, Iines 22-27.

3. The pharmacology showing that the authors are studying....

This paper was already published in NeuroReport (1992; 3, 633-636). We enclosed a reprint of the paper.

4. The biphasic response in Fig.6C is. . . ?

Such biphasic response was sometimes observed. The biphasic K+ current was also sometimes observed when Ca2+-activated K+ current was induced by externally applied caffeine. Caffeine is known to recruit intracellular Ca2+ directly from the Ca2+ store. We thought that the releasing of Ca2+ from the store was influenced by the slight differences among experimental conditions (e.g., difference in cell viability).

5. While the transduction mechanism described here is novel for 5-HT, . . .

We mentioned and cited the paper (Higashida and Brown, Nature 323, 333, 1986) such as p. 14, Iines 12-14.

6. Thanks for your kind comments. We corrected the English language, according to your suggestions.

I hope our responses are satisfactory, and we look forward to hearing from you again. Thank you for your attention and consideratior in this matter.

Sincerely yours,