Pathways in the emergence of developmental neuroethology: Antecedents to current views of neurobehavioral ontogeny

The historical forces that have contributed to our current views of neurobehavioral development (and thus to the fields of developmental psychobiology and neuroethology) are many and varied. Although similar statements might be made about almost any field of science, it is in particular true of this field, which represents a kind of mongrel discipline derived from at least three major sources (psychology, embryology, and neuroscience) and several more minor ones (including developmental psychology and psychiatry, psychoanalysis, education, zoology, ethology, and sociology). Although I attempt to demonstrate here how each of these sources may have influenced the emergence of a unified field of developmental psychobiology or developmental neuroethology, because the present article represents the first attempt of which I am aware to trace the history of these fields I am certain that there is considerable room for improvement, correction, and revision of the views expressed here. Accordingly, I consider this inaugural effort a kind of reconnaissance intended to trace a necessarily imperfect historic path for others to follow and improve upon. In the final analysis, I will be satisfied if this article only serves to underscore two related points: first is the value derived from historical studies of contemporary issues in development, and the second concerns the extent to which our current ideas and concepts about neurobehavioral development, ideas often considered new and contemporary, were already well known to those who came before us. The first point underscores the arguments expressed in the Introduction that the present must always be reconciled with the past, for the past is never entirely past. The second point returns full circle to an important thought expressed in the opening quotation to this article, namely, that even though our historic predecessors lacked much of the empirical facts available to us they were nonetheless able to attain a surprisingly deep understanding of neurobehavioral ontogeny. © 1992 John Wiley & Sons, Inc.     

Calcium-dependent binding of phosphorylated human pre interleukin 1 alpha to phospholipids

The effect of phosphorylation of pre interleukin 1 alpha (IL 1 alpha) on its association with various phospholipids was investigated. We prepared genetically engineered truncated human pre IL 1 alpha (residues 64 to 271) and phosphorylated this pre IL 1 alpha in vitro by using the catalytic subunit of cAMP-dependent protein kinase. Phosphorylated truncated pre IL 1 alpha selectively binds to acidic phospholipids including phosphatidic acid, phosphatidylserine, and phosphatidylinositol, but not to other phospholipids (phosphatidylcholine and phosphatidylethanolamine). This binding required divalent cations: Ca2+ or Mn2+, but not Mg2+. In order to obtain half-maximal binding of pre IL 1 alpha to phosphatidic acid or phosphatidylserine, Ca2+ between 5 and 100 microM was required. Unphosphorylated pre IL 1 alpha did not bind to phosphatidylserine, indicating that phosphorylation is required for this binding. Phosphorylated pre IL 1 alpha did not bind to intact peripheral blood mononuclear cells irrespective of lipopolysaccharide stimulation, but did bind to membrane vesicles prepared from these cells in the presence of calcium. Furthermore, phosphorylated pre IL 1 alpha bound only to inside-out ghosts, but not right-side-out ghosts, prepared from human red blood cells. Taken together, these data suggest that phosphorylated pre IL 1 alpha binds to the inner surface of plasma membrane in a Ca2(+)- and phospholipid-dependent manner.     

Naturally occurring and induced neuronal death in the chick embryo in vivo requires protein and RNA synthesis: evidence for the role of cell death genes.

Treatment of chick embryos in ovo for 10-12 hr with inhibitors of protein and RNA synthesis during the peak time of normal cell death (Embryonic Day 8) for motoneurons and dorsal root ganglion cells markedly reduces the number of degenerating neurons in these populations. The massive neuronal death induced by the early absence of the limbs was also blocked almost completely by these agents. Further, the death of neurons following peripheral axotomy at the end of the normal cell death period (Embryonic Day 10) was reduced significantly by treatment with inhibitors of biosynthetic reactions. These results indicate that, in vivo, naturally occurring neuronal death, neuronal death induced by the absence of peripheral targets, and axotomy-induced neuronal death later in development all require active gene expression and protein and RNA synthesis. Therefore, neuronal death in a variety of situations may reflect the expression of a developmental fate that can normally only be overridden or suppressed by specific environmental signals (e.g., neurotrophic molecules).     

Defective Fc-mediated phagocytosis in C3H/HeJ macrophages. II. Correction by cAMP agonists

Peritoneal macrophages from LPS hyporesponsive C3H/HeJ mice lose the capacity to bind and phagocytose opsonized sheep erythrocytes (EA) over a 48-hr culture period. This loss in Fc receptor capacity is markedly different from the progressive increase in phagocytic ability exhibited by cultured macrophages derived from LPS-responsive C3H/HeN mice. Since dibutyryl-cyclic adenosine monophosphate (DBcAMP) has previously been reported to modulate membrane receptor expression in lymphocytes and certain macrophage-like cell lines, we examined its effects on EA binding and phagocytosis by C3H/HeJ macrophages. DBcAMP not only reverses the binding defect in C3H/HeJ macrophages but also restores EA phagocytosis to the level of control C3H/HeN cultures. 8-Bromo-cAMP, as well as other agents known to elevate intracellular cAMP (i.e., isoproterenol plus isobutylmethylxanthine or prostaglandin E2) also corrected the phagocytic defect. Since the C3H/HeJ macrophage phagocytic defect can also be reversed by in vitro stimulation with a lymphokine-rich culture supernatant, we examined the effect of this treatment on intracellular cAMP levels. Lymphokine treatment produced a 60% increase in the levels of macrophage intracellular cAMP. These findings suggest that the C3H/HeJ differentiation defect may be secondary to some abnormality in a cAMP dependent pathway.     

Repression of ant synthesis early in the lytic cycle of phage P22

Summary Using SDS-polyacrylamide gel electrophoresis to study the early expression of P22 genes we show that early expression of the ant-gene (imm I region) is turned off after 6–8 min, independent of the late acting mnt-repressor. A semi-clear mutant called cir5 is defective for this early ant turn-off. The mutation cir5 maps in the imm I region of P22 between genes mnt and ant. P22 cir5 mutants are defective for a repressor which acts in trans to regulate early ant synthesis. There appears to be no absolute requirement of the cir5 allele for the establishment of lysogeny. The overproduction of ant in the P22 cir5 mutant leads to a marked increase in abortive infections, killing the infected cells. The cir5-phenotype can be suppressed by an ant ^- mutation.     

Analysis of a temperature sensitive mutation in gene cII of bacteriophage lambda

Summary The mutation cIIts612 was found to map outside the immunity region of phage imm21 hybrid. As expected of a cII mutation, cIIts612 is unable to stimulate either cI repressor or Int synthesis during the establishment of lysogeny. These results indicate that part of the cII gene of is homologous to that of imm21 phage.     

Low frequency of (5''-3'') -C-G- connection in 70S RNA from simian sarcoma virus.

The frequency of oligonucleotides obtained from simian sarcoma virus RNA by digestion with ribonuclease T1 was compared with the frequency expected of an RNA molecule in which nucleotides are arranged in random distribution. Oligonucleotides containing C-residue attached to 3'-Gp were found significantly less in simian sarcoma virus 70S RNA than expected by random distribution.