191 2 



ii Winn ii iK ' il I'livsii il <><;v 



NEUROPHYSioi OGY in 



mi'iii pathways is quite literally 'congenital, 9 or 

 'present from the beginning.' 2 Chromosomes are in 

 pan composed of chains of segmented nucleotides 

 and ii is hypothesized that these act as templates for 

 forming cellular proteins and that their molecular 

 configurations provide a highly refined "code" for 

 determining all that is implied by genetic specificity 

 (ii, 16). Precisely how this intricate process of early 

 protein production and the interactions of chemical 

 processes ultimately leads to the formation of an 

 alligator, a chicken, a phenylketonuric idiot or a 

 normal man is only beginning to be understood. The 

 codes normal for a given species can be and are con- 

 stantly changed or 'mutated', the mutation in the 

 chromosome may be thought of as leading to mutated 

 proteins which in turn lead to biological variation or 

 frank abnormality in development, depending on the 

 degree of deviation. That segments of chromosomes, 

 large and small, are ultimately responsible for recog- 

 nizable characteristics or groups of characteristics 

 in the adult organism is unquestioned, hut there is no 

 way of projecting 'straight lines' from genes to organs 

 or to discrete functional units. There is not a gene for 

 the brain, another for an arm, etc. Rather, seemingl) 

 unrelated structures may depend on the integrity of 

 what seems to be a single genetic process. Some groups 

 of structures may possibly depend on a constellation 

 of genes in several chromosomes, a defect in any one 

 of the different parts of the constellation leading to 

 the same or a closely related abnormality. The 

 hereditary ataxias, with their involvement of certain 

 parts of the neuromuscular apparatus, may represent 

 such a process 



Most spontaneous abnormalities arise from primary 

 mutations or as a result of interference from the en- 

 vironment with genetically determined pathways of 

 development. Abnormalities may express themselves 

 at gross structural, biochemical or functional levels. 

 Winn an environmentally triggered abnormality 

 imitates a mutant, it is called a phenocopy. Some 



mutations an- not expressed without the help of an 



environmental factor so that the distinction between 

 the effects ol mutations and phenocopies ma\ not 

 alwavs In- sh.np. A third class of abnormalities, 

 essentially anatomic, ma\ result from frank destruc- 

 tive injury to the embryo (19, 24). The) an- not 

 phe npies in the sense above hut rather reflect 



what happens to an\ 'normal' vertebrate when parts 



of it are destroyed during ontogeny. It might he said 

 r li.it such injuries bring out responses thai reflect 



,ii ,1 !. 1 in this chaptei "ill 11 «'. 1 11 develop- 

 mental ili-ui det 



more the genetic similarities of developmental 

 processes common to vertebrates than subtle mutant 

 differences between individuals. Contrary to some 

 popular medical and lay opinions, few instances of 

 this class of anomalies are known outside of the 

 laboratory. A well-known experimental example is 

 damage to the prechordal mesoderm of embryos of 

 amphibia, birds and mammals which results in 

 degrees of head and brain anomalies, depending on 

 how the experimenter inflicts the damage. Perinatal 

 asphyxia in man and mammals, mechanical injuries 

 (experimental and otherwise I, and ionizing radiation 

 may produce this class of abnormalities mo by de- 

 stroying certain tissues in the embryo. 



In the evolution of the vertebrate nervous system, 

 which seems to have been the supcrimposition of 

 increasingly complex associative devices on a simple 

 receptor-effector axis (18), the patterns of early onto- 

 genesis have remained rather similar among the man) 

 present forms. Cleavage and formation of a blastula 

 lead to a situation where an ectodermal layer or 

 epiblast comes to overlie mesodermal cells and the 

 latter induces the former to become a neural plate 

 (34). This early plate can be shown by experiment to 

 possess potentialities for an anterior brain or arch- 

 encephalon and a posterior part or brain stem and 

 spinal cord. These potentialities are scarcely evident 

 before a much more extensive mosaic of future regions 

 of the nervous system can be anticipated in the plate 

 and its adjacent neural crest As the plate rolls up 

 into a tube, a pattern of successive series of prolifera- 

 tion centers appears in the mitotic cell layer of the 

 tube and from these the whole central nervous system 

 evolves These early patterns are remarkably similar 

 amongst the vertebrates as a whole (8). Each center 

 gives rise to one or several bursts of proliferation and 

 resulting cells migrate out appropriately to form 

 layers of the pallium, the nuclei of the interbrain, the 

 brain stem and the spinal cord. The processes of the 

 neurons form the liber sv stems and nerves. 



Yeiv early in embryonic life a sequence of self- 

 determining processes becomes evident in the func- 

 tional organization of the nervous system that leads 

 to a specificity that almost makes each nerve cell in 

 the bod) different from ever) other. Although one 

 can interchange parts of the early embryonic neu- 

 raxis ami the exchanged parts will rearrange their 

 potentialities so th.it a nearlv normal animal develops, 



this facult) lor structural readjustment is lost as 



differentiation proceeds When a motor nerve first 



mows into its muscle ii takes on a specificity, appar- 

 ently at the molecular level, that identifies il with 



