102 INTRODUCTION TO NEUROLOGY 



nerve-cells, (5) fatigue of the synapses between the nerve-cells, 

 (0) fatigue of the sense organs and afferent apparatus, (7) fatigue 

 of the centers of voluntary control. The first, second, fourth, 

 and fifth types commonly play a part in ordinary fatigue, the 

 third is insignificant, and the sixth and seventh may be present. 

 The synapses and the motor end-plates are probably especially 

 susceptible to fatigue of depression by toxic substances, and the 

 muscle-fibers and nerve-cell bodies to fatigue of excitation by 

 consumption of their material. 



A resting neuron when excited to activity at first increases in 

 size by reason of the stimulus given to general metabolic activ- 

 ity. The first signs of fatigue result from the exhaustion of the 

 oxygen supply of the cells; then follows the consumption of the 

 reserve food materials, chiefly those represented in the chromo- 

 philic substance, with consequent shrinkage of the Nissl bodies. 

 In extreme fatigue the ultimate dissolution and death of the cell 

 may be hastened by the accumulation of toxic products of cell 

 metabolism. 



It appears to be well established by numerous experimental studies that 

 at the beginning of functional activity both the nucleus and the cytoplasm 

 of the resting neuron are enlarged, and that with the onset of fatigue 

 there is a shrinkage, especially of the nucleus, with vacuolation of the 

 cytoplasm and solution of the Nissl bodies due to the consumption of the 

 chromophilic substance during activity. The neurofibrils are also said to 

 be modified during functional activity. After excessive activity they be- 

 come more slender and apparently increase in number, while during rest and 

 after hibernation of those animals which have this habit the neurofibrils 

 become thicker and less numerous. 



Cells whose chromophilic substance has been consumed by active 

 function may after rest return to the normal form; but if the excitation be 

 carried beyond the stage of normal fatigue, recovery of the neuron is im- 

 possible and it gradually disintegrates, resulting in the permanent enfeeble- 

 ment of the nervous system. 



The observations of Dollcy have suggested to him that the volume of the 

 nucleus bears a constant relation to the volume of the cytoplasm in all 

 resting nerve-cells of the same type. In varying functional states of excita- 

 tion and depression this mass relation is disturbed in accordance with the 

 formula: Activity finally results in a disturbance of the normal nucleus- 

 cytoplasmic relation in favor of the cytoplasm (fatigue of excitation), while 

 depression resulting from accumulated toxins finally results in a disturbance 

 of this relation in favor of the nucleus. In short, the depression of the 

 neuron by any form of intoxication or otherwise gives the converse picture 

 of structural changes from that presented by fatigue of excitation. 



Most of the physiological work which has been (lone upon fatigue has been 

 directed toward the isolation of special toxic substances such as in Dolley's 

 scheme would produce "fatigue of depression." It has been shown that 



