Olfactory bulb removal eliminates maternal behavior in the mouse.

Olfactory bulb removal eliminated maternal behavior in lactating and in virgin mice. The results are in contrast to the generally accepted concept of multisensory control of mammalian maternal behavior.

Infantile stimulation induces brain lateralization in rats.

The hypothesis tested was that the effects of early experiences are asymmetrically distributed in the two brain hemispheres. Litters were either handled or not handled between birth and weaning, and the weanlings were reared in either laboratory cages or enriched environments between 21 and 50 days. When approximately 135 days old, animals within each of the four treatment groups had a right neocortical ablation, a left neocortical ablation, a sham operation, or no surgery. About 1 month later, all animals were given the open-field test for emotionality and exploratory behavior. Ablating either the right or left neocortex increased the activity scores of nonhandled controls, but there was no evidence of lateralization. However, the groups handled in infancy did show lateralization. Ablating the left brain did not significantly increase activity, but ablating the right brain caused extreme scores: handled rats without enrichment experience were the most active, and handled rats also placed into the enriched environment had near-zero scores in the open field.

Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. N-terminal asparagine and glutamine are tertiary destabilizing residues, in that they are enzymatically deamidated to yield secondary destabilizing residues aspartate and glutamate, which are conjugated to arginine, a primary destabilizing residue. N-terminal arginine of a substrate protein is bound by the Ubr1-encoded E3alpha, the E3 component of the ubiquitin-proteasome-dependent N-end rule pathway. We describe the construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (Nt(N)-amidase), encoded by the Ntan1 gene. In wild-type embryos, Ntan1 was strongly expressed in the branchial arches and in the tail and limb buds. The Ntan1(-/-) mouse strains lacked the Nt(N)-amidase activity but retained glutamine-specific Nt(Q)-amidase, indicating that the two enzymes are encoded by different genes. Among the normally short-lived N-end rule substrates, only those bearing N-terminal asparagine became long-lived in Ntan1(-/-) fibroblasts. The Ntan1(-/-) mice were fertile and outwardly normal but differed from their congenic wild-type counterparts in spontaneous activity, spatial memory, and a socially conditioned exploratory phenotype that has not been previously described with other mouse strains.

Behavioral characterization of mice lacking the ubiquitin ligase UBR1 of the N-end rule pathway.

The N-end rule pathway, a subset of the ubiquitin pathway, relates the in vivo half-life of a protein to the identity of its N-terminal residue. Mice lacking NTAN1, a component of the N-end rule pathway, showed altered learning and memory, and socially conditioned behavioral alteration (Balogh, Kwon, & Denenberg 1999, 2000; Kwon, Balogh et al. 2000; Balogh et al. 2001). Mice lacking UBR1 (E3alpha), one of at least three recognition components of the N-end rule pathway, are viable and outwardly normal. Here we describe behavioral characterizations of UBR1 knockout (UBR1-/-) mice. Compared to congenic littermates, UBR1-/- mice exhibited less spontaneous activity in an open field and took longer to locate the hidden platform during eight-week Morris water maze retention. In contrast, they performed better in horizontal-vertical discrimination and Lashley III maze testing. No statistically significant differences in inhibitory learning were observed. With the exception of enhanced Lashley III maze performance, these data parallel findings with NTAN1-/- mice lacking the upstream component of UBR1. These results suggest that, like NTAN1, UBR1 is involved in learning and memory.

Multiple dimensions of handedness and the human corpus callosum.

Consistency of right-hand preference correlates with callosal isthmus size. Anterior corpus callosum (CC) regions vary as a function of sex and right- versus left-hand preference. We analyzed regional CC anatomy in a sample of right- and left-handed men and women on the basis of both degree ("Consistency") and direction ("Hand") of hand preference scores. Significant Hand x Consistency effects indicated that both are important factors in CC organization. These data also suggested that a single continuum of hand preference and regional CC size may not be applicable across all subjects.

Effects of the non-pseudoautosomal region of the Y-chromosome on behavior in female offspring of two congenic strains of mice.

The learning behavior of female offspring of two strains of mice congenic for the Y-chromosome, BXSX/MpJ-Yaa and BXSB/MpJ-Yaa+, was examined. Significant differences were found in the Morris water maze and the Lashley III maze, demonstrating that the fathers' Y-chromosome can indirectly affect their daughters' behavior. Approximately half the mice had neocortical ectopias, and females from the two paternal groups reacted differently to the presence or absence of ectopias. Since females do not have a Y-chromosome, these effects must be through non-genetic mechanisms. Prenatal factors that could have played a role include possible differences in gonadal growth and the presence of different H-Y antigens. Postnatally, the sires and male siblings of the two strains may not have behaved the same toward the female offspring and/or the dams, creating differences in behavior. In summary, the behavior of female offspring of two groups of males, genetically the same except for their Y-chromosomes, was examined. Since females do not receive a Y-chromosome from their fathers, in theory their behavior should not differ. Significant differences were found, indicating that the Y-chromosome, through some indirect mechanism, can affect females of the next generation.

Evidence for a functional role for active (REM) sleep in infancy.

Roffwarg et al. have proposed two complementary hypotheses to account for the finding that rapid eye movement (REM), or Active, Sleep occurs in large quantities in infancy and then drops off as the organism matures. The first assumes that the immature nervous system lacks inhibitory control and that the diminution of REM sleep reflects the maturation of the CNS. The second hypothesis postulates that REM sleep also serves a functional role, namely, to stimulate the central nervous system, thereby facilitating growth and maturation. A set of deductions, derived from the second hypothesis, was tested by analyzing the sleep-wake data of 22 normal infants. These were confirmed. The key findings were that the behavioral state of Quiet Alert correlated -0.82 with the state of Active Sleep and that this correlation was independent of maturational changes in the infants.

Estradiol facilitates performance as working memory load increases.

A water-escape version of the radial-arm maze was used to assess rat spatial working memory performance. Intact females and ovariectomized females receiving a physiologically low dose, physiologically moderate dose or no estradiol replacement were studied. Subjects were given seven trials a day for 12 days. Females receiving moderate dose estradiol made fewer errors than the other three groups during the latter portion of testing. As trials progressed within a session, the elements of information to be remembered increased. Assessment of individual trials revealed that when the demand on an animal's working memory system was limited to one to four elements of information, the three groups with estrogen (including intact females) maintained successful performance, whereas the ovariectomized females made more errors. However, when the demand on an animal's working memory system was increased to six elements of information, only the moderate dose estradiol females maintained successful performance. These data suggest that, although moderate levels of estradiol replacement are the most beneficial for working memory function, even low-dose estradiol replacement can act to protect working memory systems from the decline seen with the removal of ovarian hormones.

Corpus callosum: interactive effects of infantile handling and testosterone in the rat.

Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level.

The uterine environment enhances cognitive competence.

Genetically identical mouse embryos were transferred into same-strain uteri (transfer controls) or into hybrid uteri. A third group was not transferred. When adult, the mice were given a series of behavioral tests. In-strain transfer controls differed from non-transfer mice only on two activity measures, and did not differ on any cognitive variable. In contrast, mice reared in hybrid uteri were found to be superior to in-strain transfer mice on discrimination learning, Lashley maze learning and Morris maze learning; they also showed better adaptation in an avoidance learning shuttlebox. To our knowledge this is the first study showing that the uterine environment can have a general enhancing effect upon cognitive competence across a broad range of behaviors.

The uterine environment enhances cognitive competence.

Genetically identical mouse embryos were transferred into same-strain uteri (transfer controls) or into hybrid uteri. A third group was not transferred. When adult, the mice were given a series of behavioral tests. In-strain transfer controls differed from non-transfer mice only on two activity measures, and did not differ on any cognitive variable. In contrast, mice reared in hybrid uteri were found to be superior to in-strain transfer mice on discrimination learning. Lashley maze learning and Morris maze learning; they also showed better adaptation in an avoidance learning shuttlebox. To our knowledge this is the first study showing that the uterine environment can have a general enhancing effect upon cognitive competence across a broad range of behaviors.

Analysis of two measures of paw preference in a large population of inbred mice.

Two measures of lateralized forelimb usage, the Collins paw preference test and the Lateral Paw Preference test (LPP), were tested in 693 mice of 29 inbred strains and F1 crosses, and 2 embryo transfer groups. These strains included NZB, SM, and the NXSM recombinant inbred (RI) strains; RF and the NXRF RI strains; BXSB and the Y-consomic BXSB-Yaa+; DBA/2 and F1s of DBA/2 and BXSB and BXSB-Yaa; and NZB x NZW F1s. The findings indicated that (1) the Collins and LPP tests were independent in terms of direction of lateralization, (2) there were significant population biases of 60.96% rightward on the LPP test, and 54.39% leftward on the Collins test, (3) there were significant strain differences on measures of absolute asymmetry on both tests, (4) there were strain differences for direction of asymmetry on the Collins test, but not on LPP, (5) on the basis of the NXSM RI strains, 3 genetic loci contribute to strength of laterality on the LPP test, and (6) there was a strong correlation among strain means for strength of lateralization on the two tests. These results extend previous findings on the strength and direction of laterality, showing that two independent systems for direction of laterality may depend on the same mechanism for magnitude, and establish that multiple factors of handedness, previously identified in humans and other primates, also exist in mice.

Effects of cortical ectopias on spatial delayed-matching-to-sample performance in BXSB mice.

BXSB mice have small neocortical anomalies (ectopic collections of neurons in layer I), with an incidence of about 40-60%. Previous studies have found that ectopic mice from this strain are faster than non-ectopics in learning the Morris water maze (reference memory), but have poorer working memory for spatial learning. The current study continues the investigation of working memory by testing ectopic and non-ectopic BXSB mice on a spatial delayed-matching-to-sample test (S-DMTS; also called spatial learning sets or 'working memory' water maze). In this test, the mice must find a submerged platform in a pool of water. The platform changes location with every problem, or block of four trials. The subject has 'matched to sample' if it locates the platform in less time on the second trial of each problem than it did on the first. Of 33 subjects, 8 had cortical ectopias, one had a small neuron-free gliotic area, and 24 were normal. The normal subjects showed a decrease in time to escape over the first 2 trials of the first 5 problems, while the ectopic subjects did not show a decrease until the third trial, indicating that ectopic mice required more trials to put the platform location into working memory. The site of the ectopias is prefrontal/motor cortex, and we hypothesize that is the cause of the poorer working memory.

Handling in infancy, brain laterality and muricide in rats.

Rats were handled for the first 20 days of life or were not disturbed. Between 21 and 50 days approximately half of each group was reared in enriched environments while the remainder was group reared in laboratory cages. When adult, four males from each litter received a right neocortical ablation, a left ablation, a sham operation, or no surgery. They were tested for mouse killing between 9-12 months of age. Intact non-handled controls without enrichment experience had a 96% incidence of muricide. Handling and enrichment treatments independently and additively reduced the rate of mouse killing in animals with intact brains. There was no evidence of brain laterality for animals which received no extra stimulation in early life. In contrast, the brains of handled animals were lateralized, with the left lesion group having a higher killing response than the right. Non-lesioned handled rats had approximately the same level of muricide as those with a right hemisphere lesion, leading to the inference that in the intact brain the left hemisphere inhibits the killing response of the right.

Spatial ability of XY sex-reversed female mice.

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y(POS) consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y(POS) strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.