26 VICTOR E. SHELFORD AND W. C. ALLEE 



oxygen, where respiratory changes have been definitely timed 

 (table 3). Our evidence indicates that peripheral stimulation 

 is not of supreme importance in the regulation of breathing, 

 because the fishes reacted definitely to a change in the water 

 before the breathing was affected. 



Bethe ('03) proposed the hypothesis that the breathing rate 

 of fishes is regulated directly by stimulation from the periphery, 

 particularly by stimulation of the mucous membrane of the mouth 

 and gills. This hypothesis has been widely tested (Baglioni, '10 

 and citations), but the more recent experimentation (Reuss, '10) 

 seems to show that the breathing of fishes is regulated indirectly 

 as in the higher vertebrates, although the suggestion of Kuiper 

 ('07) that both the automatic center and reflex stimulation are 

 concerned has much evidence in its favor. The important thing 

 in the work of the followers of Bethe from the standpoint of this 

 paper is the establishment of quickly working sense perception 

 in the mucous membranes of the gills and mouth. 



The negative reaction and modification of reaction of fishes 

 to acid may be explained in a manner similar to that presented 

 for carbon dioxide. Winterstein ('11), Signorelli ('10) and 

 Quagliarello ('11) and others report that it is the acidity of the 

 blood that affects the respiratory center and similar results are 

 nearly always obtained with carbon dioxide and other acids in 

 reversing reaction to light, etc. (Mast, '11 and citations). Ac- 

 cordingly the increased sensibility in acetic acid and in carbon 

 dioxide probably have a common explanation. 



It is well known that an insufficient supply of oxygen leads 

 to the formation of lactic acid rather than carbon dioxide as the 

 end product of respiration. Fletcher ('98), Fedman and Hill 

 ('11) and Araki ('91) report that lactic acid production bears 

 some inverse relation to oxygen supply. Signorelli ('10) found 

 that lactic acid directly affects the respiration center. 



When the fishes remain long enough in the low oxygen to affect 

 the amount of oxygen in the blood and tissues, the presence of 

 lactic acid probably results and the plasma tends toward acidity 

 just as when acids are used directly. We thus infer that in- 

 creased sensibility and the resulting modifications are due to 

 acidity just as in the other two cases. 



Ammonia is present in the blood of mammals and appears to 

 bear some relation to the carbon dioxide (Hopkins and Dennis, 



