26 BRAIN MECHANISMS AND LEARNING 



chemical, electrical, structural; and how does fixation occur, at the 

 molecular and at the cellular levels? Some attention will be given to the 

 nature and the locus of the material record, but most attention will be 

 given to the mechanism of fixation. 



A neurone, at least in tissue culture, is a restless entity. It shows the usual 

 swellings and churnings of other cells and its processes thrust out and 

 retract pseudopodial branches and terminations unceasingly. The neurone 

 has an unusually high rate of metabolism and, judging by the rate of 

 regeneration and of peripheral flow in axons, a neurone may renew its 

 entire mass of protoplasm three times daily. It is hard to see, therefore, 

 how an enduring modification can be left at the cellular level. Experience 

 must presumably alter some macromolecule, DNA or RNA or protein, 

 which can continue to reproduce itself in the altered form, much as a 

 mutated gene. But then other formidable problems arise. How docs 

 neural activity, and the particular pattern of electric currents and attendant 

 change in position and concentration of ions and polar molecules which 

 activity engenders, lead to an altered array of nucleotides or amino-acid 

 moieties in a macromolecule? How does such an altered complement of 

 macromolecules in a neurone come, in turn, to modify its future physio- 

 logical activity so as to give a new and appropriate pattern of discharges? 

 How is the specificity of the molecular change related to the specific 

 functional past and functional future in an adaptive fashion? Is a sort of 

 natural selection process in a neurone population involved; if not, we 

 again face the sort of problem raised by Lamarck. 



Whatever the answer at the molecular level, there are certainly morpho- 

 logical changes with neural activity at the levels of organelle and of cell, 

 and some of these endure for a relatively long time. The chromatolysis of 

 fatigue, with diminished Nissl substance, swollen and rounded cytoplasm, 

 and eccentric nucleus, has long been known. More recently, a change in 

 microsome number and locus arouiid the nucleus has been shown to 

 accompany changes in activity of neurones in tissue culture (Geiger, 1957). 

 The apical dendrite of pyramidal neurones becomes thicker and more 

 twisted with continuing activity. Nerve fibres swell when active (Hill, 

 1950; Tc^bias, 1952), sprout additional branches, as seen in the spinal cord 

 (McCouch ct (iL, 1958), and presumably increase the size and number of 

 their terminal knobs. New fibre branches and ccMincctions, at least, might 

 endure long enough to constitute a morphological engram. 



It is highly doubtful, both from the total number of bits remembered 

 and from the survival of memories despite extensive brain lesions, that 

 each remembered item is located at a particular neurone or synapse. Some 



