Transduction of Neuronal Electric Response to Macromolecular Synthesis: A Theoretical Construct of a Fundamental Unit for Information Storage and Retrieval

TRANSDUCTION OF NEURONAL ELECTRIC RESPONSE TO MACROMOLECULAR SYNTHESIS: A THEORETICAL CONSTRUCT OF A FUNDAMENTAL UNIT FOR INFORMATION STORAGE AND RETRIEVAL G. RICHARD VAN SICKLE* and ROBERT H. McCLUERf I.Macromolecular Synthesis in Neurons Developments in the elucidation of the genetic code strongly suggest that a linear permutation ofthe four nucleotide bases ofDNA molecules provides the information giving rise to the fundamental qualities of life [I]It has been repeatedly postulated since the work ofKatz and Halstead [2] thatjust as DNA molecules store genetic information, there may be a particular class ofmolecules that stores the information ofexperience (memory ) acquired during the life ofan individual [3-7]. There is considerable interest in the construction of models of information storage. The most prevalent concepts envision an RNA or protein storage form and the task ofthe model is to explain the transduction ofthe nerve input into a relatively permanent chemical form which allows information retrieval. Schmitt [8] has summarized theories on the mechanism of the transduction ofsensory input into an RNA engram. In brief, the electrical effect of a sensory input may be exerted upon a biosynthesized active steady-state system either by alteration of the sequence of nucleotides incorporated from a pool ofprecursors at the moment oftransduction, or by alteration ofthe length ofthe macromolecule without changing the residue sequence in the synthesized fragment. II.RNA and Protein Synthesis There is experimental evidence which suggests that both RNA and protein are involved at some stage in the storage ofinformation. Hydén [9] in * Department ofPsychiatry, Ohio State University, Columbus. t Departments ofPsychiatry and Physiological Chemistry, Ohio State University, Columbus. 425 order to study the effects oflearning on RNA metabolism examined nerve cells in the Dieter's nucleus of rats which had been taught to climb and balance on an inclined wire. He found an increase in the adenine/uracil ratio ofneuronal nuclear RNA as compared to non-specifically stimulated animals. Morrell and his coworkers [io] have found that a chemically produced primary cortical epileptogenic focus bombards normal cells in the opposite hemisphere through callosa! fibers. These normal cells then develop a permanent alteration of excitability such that they become capable of selfsustained , paroxysmal epileptiform discharge. This phenomenon has been interpreted to mean that afferent impulses caused the cells to "learn" to be epileptogenic. Cutting ofthe appropriate callosal fibers prior to chemical induction of the primary focus, prevents the secondary lesion from developing . In the induced secondary lesion produced by neuronal impulses, very heavy uptake ofmethyl green pyronin could be demonstrated. Pretreatment oftissue sections with ribonuclease prevented the staining, indicating that the increased dye uptake is a measure ofRNA content within the neurons of the induced epileptogenic focus. Evidence was also obtained that the cells ofthe secondary focus showed a permanent increased excitability. Neuronal isolation ofthe secondary region resulted in disappearance ofspontaneous epileptiform discharge, and such isolated regions remained quiescent for several months. When seizure discharges were elicited in the surrounding normal cortex, independent self-sustained discharge developed in the isolated region after considerable delay. Since such evidence of similar activation does not occur in isolated non-epileptic tissue, the behavior ofthe isolated secondary focus indicated that increased excitability had persisted despite the long period ofinactivity. Chamberlain et al. [??] have studied the acquisition of postural asymmetry . Rats develop postural asymmetry in the legs when a unilateral cerebellar lesion is made. The effect is apparently due to an asymmetric barrage ofimpulses coming down the spinal cord. Ifthe cord is cut, the defect is abolished unless the defect had been present for a period oftime. After 45 minutes the postural defect is not abolished by cord section, leading one to believe that neuronal impulses have provided a permanent change in the spinal motor neurons in a manner analogous to Morrell's work with epilepsy. A compound, 8-azaguanine, which inhibits RNA synthesis, prolongs the time from 45 to 70 minutes during which asymmetry can be 426 G. Richard van Sickle and Robert H. McCluer · Neuronal Electric Response Perspectives in Biology and Medicine · Spring 1966 abolished by cord section. In an opposite manner, U 9189 (Upjohn), a malononitrile dimer which enhances RNA synthesis, shortens fixation time to 25 minutes. Flexner et al. [12] have shown that puromycin, which...