NKl rophysiology: an integration 



1933 



properties are well known [see for example tempera- 

 ture block (Zotterman), sensitivity to glucose lack 

 (Hillarp), physiological specificity (Lloyd) and chem- 

 ical specificity (Ingram, Ortmann)]. Age differences 

 are striking (260, 288). 



chemical considerations. Most striking differences 

 are in the neurons themselves, in size, structure, 

 composition and metabolism, and physiological 

 properties. Details are scant on the functional side, 

 largely uninterpreted on the morphological one. 

 The clearest evidence is probably at the chemical 

 level, since different regions are differentially and 

 fairly specifically destroyed by different lacks (Brozek) 

 or additions. Ingram adds the case of goldthioglucose, 

 which destroys the ventromedial thalamic nuclei, 

 to many others that have been gathered (8f>, 91, 

 1 1 g) . Poliomyelitis virus attacks anterior horn colls 

 primarily, streptomycin or thiamin lack hits the 

 vestibular nucleus. Carbon disulphide dissects out 

 the caudate nucleus, alcohol demyelinates the mam- 

 millary bodies, carbon dioxide acts on the striatum, 

 hypoglycemia fires the amygdala, and low oxygen 

 blocks the globus pallidus. Various vitamin defi- 

 ciencies initiate degenerations in different portions 

 of the nervous system, even in different portions of a 

 neuron. Dendrites are rich in enzymes and poor in 

 Nissl substance compared to perikarya, and myelin 

 on axons in peripheral nerve ( lipid 1 differs from thai 

 in central axons (lipoprotein) (Tower). Autonomic 

 centers are resistant to oxygen and sugar lack, and 

 rich in catechol amines. Aldosterone secretion ac- 

 tivator is concentrated in the posterior dienccpha- 

 lon (69); specific neurosecretory regions exist (Ort- 

 mann); and different neurons are specifically sensi- 

 tive to changes in blood temperatures, salts, sugar, 

 gases and hormones (Harris) The reticular formation 

 is easilv depressed by hypnotics, and different regions 

 in it are specifically sensitive to the epinephrines or 

 acetylcholine (French); and so on and on. Since the 

 basic metabolic processes are alike, in liver and mus- 

 cle and brain cells, these differences are remarkable 

 and presumably of functional importance. 



With microtechniques for studying potentials and 

 discharges of single cells and for applying drugs di- 

 rectly to them [e.g. Curtis & Watkins (53)], there is 

 increasing evidence for different pharmacological 

 sensitivities of various cells and even cell parts. Single 

 receptor cells of insects respond differentially to 

 different concentrations of sugar and of salt (Pfaff- 

 man), and a retinal receptor can discharge different 

 impulse trains to different colors (125). Only Ren- 

 shaw cells are known to respond to acetylcholine, 



many others clearly do not [but see Marrazzi (193)]; 

 and various cord or cortex cells, motor or inter- 

 neurons, respond differently to GABA and to other 

 amino acids. Strychnine affects potentials of a given 

 cerebellar neuron as produced by impulses over 

 some paths but not others (234), and influences other 

 cells not at all (173). Inhibition in mammalian 

 neurons seems to be associated with an increased 

 membrane conductance to CI - (70), while in crus- 

 tacean cells the conductance change involves rather 

 K + (64). Cord and cortical neurons, and apical 

 and basal dendrites, differ in the locus and kinds of 

 mitochondria and in physiological properties [see 

 Roberts (248)]. In general there is ample evidence 

 that various membrane sites, and internal regions, 

 can differ from cell to cell and from place to place 

 in one cell even with age for a given cell type — as 

 10 structure, composition, and drug and other chem- 

 ical sensitivity, and as to permeability, potential, 

 ion gating and other physiologically important 

 properties (Grundfest, Tasakii. 



Sue h chemical specificities are important in allow- 

 ing generalized messages from the organism to 

 affect the nervous system differentially. Here lie 

 the links between chemical and neural homeostatic 

 mechanisms, engaging the nervous system by dis- 

 placement of the body's physiological constants, as 

 well as by such special endocrine responses as the 

 adrenal steroids and catechols released in stress, the 

 thyroid hormone increase with low temperature, 

 and the gonadal products that trigger behavior. By 

 such chemically receptive neurons the basic bio- 

 logical drives become converted into patterns of 

 appropriate behavior. An interesting suggestion 

 (Pribram, Stellar) relates the highly branched and 

 large-surfaced neurons of the visceral nervous system, 

 and the rich vascularization of these centers, to their 

 sensitiveness to transported signals. Moreover, slow 

 and prolonged potential changes are evoked in them 

 by blood changes (Strom, French). 



The anesthetics seem to depress generally and 

 their differential effects depend on quantitative 

 gradients in the nervous system. The more subtle 

 psychoactive agents must depend more on qualitative 

 differences, as must certain regional disorders as the 

 lenticular degeneration of Wilson's disease or the 

 combined cord degeneration of pernicious anemia. 

 As already indicated, it seems a reasonable hope 

 that functional subsystems of the nervous system are 

 al least somewhat specific chemically, and that the 

 neurotropic and psychotropic drugs will be able to 

 reveal them by a type of chemical rather than of 

 anatomical dissection [e.g. Olds (221-223)]. 



