Study of data in the literature on rat and mouse brain growth from birth to weaning reveals a stagewise growth in average brain weight. Rapid growth occurs in the intervals between days 0–6, 8–12, and 17–23 after birth. Slow growth periods then lie in the intervals 6–8, 12–17, and after 23 days. The first slow growth period is signalled by events occurring at its end: substantial acceleration of synthesis of RNA, DNA, protein, and myelin. The second slow growth period is characterized by at least a 3-day interval during which there is very little increase in average brain weight compared with what occurs just before and just after that period; the correlation among 12 studies is highly significant. Implications are discussed for cross-species’ extrapolation of findings about brain development.

tham , Massacli use t tsSpurts in the mental age of humans are shown to be recoverable from data giving the average mental age as a function of chronological age. Data from 13 independent studies are shown to give a highly consistent spectrum of ages at which spurts are found; these are 2 4 , 6-8, 10-12. and 14-16, with an especially clear low rate of growth at 12-14 yr. These ages correlate very well with those found for spurts in brain and skull sizes so that an obvious working hypothesis is that mutations for increased brain weight were selected for by virtue of the greater mental ability thus afforded to humans.One of the basic problems in the study of intellectual development in humans is that of ascertaining the existence of so-called critical periods. We focus our investigation on the evidence that mental growth in individuals increases in characteristics periods. We shall use the term phrenoblysis to describe both brain and mind spurts. The criticality of the periods will be considered in the discussion.Measurements of IQ are readily made but their interpretation is not simple. We shall avoid the problem of interpreting IQ by returning to its original functional definition as a parameter whose value indicates the likelihood that its possessor will or will not do well in conventional schools. Thus, we will call this measure the schooling quotient (SQ). The numerator of the SQ gives the comparison number which tells us how far along the individual is in terms of the age (or grade) with whose schooling problems he can readily cope; we will call this numerator the grade age (GA). When the GA is divided by the chronological age (CA) we obtain the SQ. This revised terminology is not being adopted to cater to the sensibilities of those having low IQ's; it is adopted because the argument about intelligence and intelligence quotients is currently an operationally meaningless one. On the other hand, performance in conventional schools is an approximately determinable parameter and lacks the overtones and undercurrents associated by many persons with the term IQ.One of the questions that arises is how to determine the possible periods of spurt in SQ when the tests are standardized precisely so as to give the average child of any CA a G A of the same numerical value. The main reason one can determine spurts may derive from the mechanics of standardizing SQ tests. McNemar (1942) points out that the 1916 Stanford-Binet tests were standardized on about 1000 children with about 50 children at each age, half from each sex, all from California or Nevada. These tests cannot be expected to apply at all rigorously in Maine, Maryland, or Mississippi. For the various

Our studlies wvith Euglena (2, 6, 14, 19, 20) have suggestedl that dark-grown cells containi approximately 30 proplastids whiclh develop into about 10 chloroplasts xvhen the cells are exposed to light. The existence of these proplastids, originally inferred from studlies on ultraviolet inactivation ain(l photoreactivation of chloroplast formiiation (14, 19). was confirimie(I by fluorescence ani(I electron miiicroscopy (2, 6). Other workers have stu(lie(l some of the initial steps invTolved wvhen dlark-groxvn cells are exposed to light, suclh as the conversion of protochlorophyll to chlorophyll (17). Other studies also exist of the related problemii of the physiology of chloroplast development in highler plants (3, 7, 23, 27). Our earlier vork (20) also showed that chloroplast development in Euglena could be separated experimentally into 2 phases: replication of the system which nmanufactures the chloroplast ancI development of the proplastid into the mature chloroplast. In this study x-e correlate the onset and kinetics of pigment formlation., O. evolution and COi. fixation with the developmilenit of the proplastid inito the mature chloroplast. Materials and Methods GroTl/t of Euglenia. Euigleina gracilis var. bacillaris Prinlgslheim (14) xv-as maintained aseptically in the (lark at 250, for 1 year in 250-ml Erlenmeyer flasks containiing 100 ml of Hutner's meclium pH 3.5 (10) xvith 5-ml transfers every 3 days. The starting culture wN-as a dark-grown stock maintainedl in our laboratory for over 2 years (14). The imiiportance of prolonged dark groxvtlh to entirely deplete chlorophyll and chloroplast structures has been repeatedly emlphasized (14, 17); our dark-grown cells contain protochlorophyll ancI proplastids and lack chloroplasts and chlorophyll completely. All manipulations xvere carried out under a green safelight in a (larkroolmi as described I)reviously (14).

Protein synthesis has long been known to be required for associative learning to consolidate into long-term memory. Here we demonstrate that PKC isozyme activation on days before training can induce the synthesis of proteins necessary and sufficient for subsequent long-term memory consolidation. Bryostatin (Bryo), a macrolide lactone with efficacy in subnanomolar concentrations and a potential therapeutic for Alzheimer's disease, is a potent activator of PKC, some of whose isozymes undergo prolonged activation after associative learning. Under normal conditions, two training events with paired visual and vestibular stimuli cause short-term memory of the mollusc Hermissenda that lasts Ϸ7 min. However, after 4-h exposures to Bryo (0.25 ng͞ml) on two preceding days, the same two training events produced long-term conditioning that lasted >1 week and that was not blocked by anisomycin (1 g͞ml). Anisomycin, however, eliminated long-term memory lasting at least 1 week after nine training events. Both the nine training events alone and two Bryo exposures plus two training event regimens caused comparably increased levels of the PKC ␣-isozyme substrate calexcitin in identified type B neurons and enhanced PKC activity in the membrane fractions. Furthermore, Bryo increased overall protein synthesis in cultured mammalian neurons by up to 60% for >3 days. The specific PKC antagonist Ro-32-0432 blocked much of this Bryo-induced protein synthesis as well as the Bryo-induced enhancement of the behavioral conditioning. Thus, Bryo-induced PKC activation produces those proteins necessary and sufficient for long-term memory on days in advance of the training events themselves.bryostatin ͉ PKC isozymes T he requirement of protein synthesis for long-term memory has been demonstrated over several decades for a variety of memory paradigms (1-14). It was originally shown that druginduced inhibition of protein synthesis (e.g., with 5-propyluracil or anisomycin) blocked long-term memory when this inhibition occurred during a critical time interval after the training paradigm (9). It has remained a mystery as to what specific, critical proteins were so essential for memory consolidation and how their molecular regulation was so necessary for long-lasting memory storage.In many species the formation of long-term associative memory has also been shown to depend on translocation, and thus activation, of protein kinase C (PKC) isozymes to neuronal membranes. PKC activation has been shown to occur in single identified type B cells of the mollusc Hermissenda (15) with Pavlovian conditioning and a variety of mammalian associative learning protocols (16)(17)(18). Furthermore, a high-affinity substrate of the ␣-isozyme of PKC, calexcitin (CE) (19), was found within single identified type B cells to show Pavlovianconditioning-dependent increases of phosphorylation and absolute quantity (20).Consistent with these findings, administration of the potent PKC activator bryostatin (Bryo) enhanced rat spatial maze learning (21). Bryo, a macrolide lactone,...