Nervous System 



365 



The caliber of a nerve fiber is thus deter- 

 mined essentially by three factors: (1) the 

 amount of synthesis of new axoplasm in the 

 cell body; (2) the rate of its centrifugal 

 movement; and (3) the rate of its peripheral 

 breakdown. Since' the rate of movement is 

 limited by the width of the channel in which 

 it occvxrs, large nerve fibers regenerating into 

 narrower tvibes fail to gain full normal width 

 (Holmes and Young, '42; Sanders and 

 Young, '44; Simpson and Young, '45; Ham- 

 mond and Hinsey, '45). However, no such 

 limitation is to be expected during embryonic 

 growth, before firm neurilemmal tubes have 

 formed. Assuming, furthermore, rather uni- 

 form rates of catabolism, we are left with 

 the rate of central synthesis as the main 

 variable in the determination of fiber caliber, 

 which, in turn, is rather closely correlated 

 with the size of the nerve cell body. 



Factors Controlling Neuron Growth. Early 

 in development different neuron groups seem 

 to acquire constitutional growth differentials 

 which place them in different size classes. 

 Within each class itself, however, growth 

 rate and size are subject to further modifica- 

 tions which are due to extraneous conditions, 

 as illustrated in the following. 



When a nerve fiber is severed, hence dis- 

 connected from its terminal organ, the whole 

 neuron begins to atrophy (Weiss, Edds and 

 Cavanaugh, '45; Sanders and Young, '46; 

 Aitken, Sharman and Young, '47). If we 

 disregard certain acute traumatic changes 

 ("ascending degeneration," "axon reaction") 

 referable to the injury as such, the main 

 long-range effect of the loss consists of a 

 progressive reduction of the dimensions of 

 the neviron, beginning with the nucleolus and 

 spreading to the nucleus, the cell body, and 

 finally the diameter of the axon (Cavanaugh, 

 '51). Conversely, upon reconnection with a 

 peripheral organ, the dimensions enlarge 

 again. Moreover, when a neuron is "over- 

 loaded," that is, made to innervate a larger 

 volume of peripheral tissue than originally 

 (e.g., by collateral branching into a dener- 

 vated field), nuclevis and cell body enlarge 

 above their normal dimensions (Terni, '20; 

 Edds, '49; Cavanaugh, '51). The production 

 center of neuronal synthesis thus adapts 

 itself sensitively to the demands of the 

 peripheral innervation volume. 



Variations of functional activity have simi- 

 lar effects. Not only do neurons tend to 

 atrophy, when they are chronically de- 

 prived of excitation (e.g., Edds, '51), but 

 they hypertrophy, again starting from thp 

 nucleus, in response to intensified physio- 



logical demands (Hamberger and Hyden, 

 '49). Enlargement of the nuclei and nucleoli 

 of the cells in certain brain centers following 

 induced hyperfunction of these centers (e.g., 

 antidiuretic center in the hypothalamus) 

 has also been recorded (Ortmann, '51). The 

 interpretation of all these facts requires cau- 

 tion, because nuclear enlargement may sig- 

 nify either true protoplasmic growth gener- 

 ally associated with increase in desoxyribo- 

 nucleic acids (Hyden, '50), or merely water 

 uptake, accumulation of functional products 

 and other transitory changes subserving 

 functional activity rather than true growth 

 (see Leuchtenberger and Schrader, '52). 



At any rate, the realization that the size 

 of a neuron is subject to continual upward 

 or downward regulations in accordance with 

 extraneous influences received from both 

 its afferent and (ascendingly) efferent ends, 

 certainly controverts the classic view which 

 has endowed the central nervous system, at 

 least in morphological regards, with a nim- 

 bus of static and rigid fixity. 



The significance of this demonstrated plas- 

 ticity for our concepts of central activity is 

 evident. The backward projection of periph- 

 eral conditions into the centers, which we 

 encounter here for the first time in our 

 discussion and which will be amplified be- 

 low, is particularly noteworthy. This makes 

 it all the more important to stress the fact 

 that the reported influences do not "deter- 

 mine" activity, growth, or size, of a neuron 

 in any absolute sense, but simply enhance 

 or depress its inherent activities, and within 

 relatively narrow limits at that (for in- 

 stance, even the chronically disconnected 

 ganglion cell still retains about 60 per cent 

 of its normal mass). 



Biochemistrv of Neuron Growth. The 

 morphological evidence for the localized 

 growth of the neuron from the nuclear ter- 

 ritory (Weiss and Hiscoe, '48) is supported 

 by the cytochemical demonstration of abun- 

 dance of desoxyribonucleic acids and a high 

 rate of protein synthesis in the nuclear 

 territory (Caspersson, '50; Hyden, '50), with 

 fluctuations that closely narallel the growth 

 activity of the neuron. Thus, the intensity 

 of these syntheses increases during the re- 

 generative nhase following nerve section 

 (Bodian, '47), during the growth reaction 

 resulting from hyneractivity (Hamberger 

 and Hyden, '45) and, embryonically, during 

 the phase of the fTmctional alerting of brain 

 cells (Flexner, '50). 



In agreement with this monopoly of the 

 nuclear territory as the growth center of 



