Victor H. Denenberg

Hemispheric laterality in animals and the effects of early experience

A review of research with chicks, songbirds, rodents, and nonhuman primates indicates that the brain is lateralized for a number of behavioral functions. These findings can be understood in terms of three hypothetical brain processes derived from a brain model based on general systems theory: hemispheric activation, interhemispheric inhibition, and interhemispheric coupling.Left-hemisphere activation occurs in songbirds and nonhuman primates in response to salient auditory or visual input, or when a communicative output is required. The right hemisphere is activated in rats when spatial performance is required, and in chicks when they are placed in an emotion-provoking situation. In rats and chicks interhemispheric activation and inhibition occur when there is an affective component in the environment (novelty, aversive conditioning) or when an emotional response is emitted (copulation, attack, killing). An interhemispheric coupling (correlation) found in rats and rabbits implies that the hemispheres are two major components in a control system with a negative feedback loop. Early-experience variables in rats can induce laterality in a symmetric brain or facilitate its development in an already biased brain.It is predicted that functional lateralization, when present, will be similar across species: the left hemisphere will tend to be involved in communicative functions while the right hemisphere will respond to spatial and affective information; both hemispheres will often interact via activation-inhibition mechanisms when affective or emotional processes are involved. Homologous brain areas and their connecting callosal fibers must be intact at birth and must remain intact throughout development for lateralization to reach its maximum level. Injury to any portion of this unit will result in hemispheric redundancy rather than specialization. One major function of early experience is to provide stimulation during development, which acts to enhance the growth and development of the corpus callosum, thereby giving rise to a more specialized brain.

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 animals 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 animals 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: region-specific effects of sex, early experience and age

In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.

A role for ovarian hormones in sexual differentiation of the brain

Historically, studies of the role of endogenous hormones in developmental differentiation of the sexes have suggested that mammalian sexual differentiation is mediated primarily by testicular androgens, and that exposure to androgens in early life leads to a male brain as defined by neuroanatomy and behavior. The female brain has been assumed to develop via a hormonal default mechanism, in the absence of androgen or other hormones. Ovarian hormones have significant effects on the development of a sexually dimorphic cortical structure, the corpus callosum, which is larger in male than in female rats. In the females, removal of the ovaries as late as Day 16 increases the cross-sectional area of the adult corpus callosum. Treatment with low-dose estradiol starting on Day 25 inhibits this effect. Female callosa are also enlarged by a combination of daily postnatal handling and exogenous testosterone administered prior to Day 8. The effects of androgen treatment are expressed early in development, with males and testosterone-treated females having larger callosa than control females as early as Day 30. The effects of ovariectomy do not appear until after Day 55. These findings are more consistent with other evidence of a later sensitive period for ovarian feminization as compared to androgenic masculinization.

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.

Prolactin: Is it an essential hormone for maternal behavior in the mammal? ☆

Abstract Evidence is reviewed for the concept that prolactin is one of the essential hormones for maternal behavior in the rabbit, rat and mouse. Ergocornine hydrogen maleate prevents maternal nest building in the pregnant rabbit, but if prolactin is added to the treatment regimen, nest building occurs. In the rat, retrieval, crouching and licking of pups is obtained following treatment with estradiol, progesterone and prolactin. In the mouse, the evidence is not as strong but one laboratory has obtained retrieval following implantation of prolactin in the hypothalamus.

A developmental study of sex and age interactions in the human corpus callosum

Regional analysis of the corpus callosum (CC) has demonstrated that the development of this fiber tract is sexually dimorphic. Midsagittal CC tracings from magnetic resonance images (MRIs) of 73 pairs of age-matched (age 2-79 years) males and females were digitized using computer assisted software. Area, axis length, perimeter, and 99 widths were obtained. Widths were grouped into the following regions based upon prior factor analysis: widths 3-18 (W3-18), W22-39, W49-62, W65-74, W77-85, W89-94, and W95-99. Trend analyses were performed with Sex and Age (blocked into 10-year bins) as independent variables. Higher order Sex by Age interactions were significant in regions W3-18 and W22-39 and were marginal in W95-99. In all 3 regions, females did not attain maximum width until Age 41-50 whereas males had peaked at 20 years and declined thereafter. There were no significant interactions between Sex and Age in the remaining CC regions, nor were there any dramatic decreases once maximum width was reached in adulthood. These results suggest that sex differences may also exist in CC ultrastructure over the human lifespan.

The development of standard stimulus animals for mouse (Mus musculus) aggression testing by means of olfactory bulbectomy.

Abstract The usual round-robin technique employed in aggression testing with mice has several major deficiencies. A set of specifications is given for the ideal standard stimulus mouse, which would overcome these deficiencies. In a series of seven experiments, we found that the technique of bilateral olfactory bulbectomy yielded stimulus animals which very closely approximated our ideal. Bulbectomized mice would elicit attack behaviour from normal males, would almost never initiate an attack themselves, rarely fought back when attacked, and were very homogeneous in their capability to release attack behaviour. These findings were obtained whether the mice were tested within a few days after bulbectomy or 40 days afterwards.

In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze

Male and female mice and rats were tested on a water escape version of the radial-arm maze designed to measure working and reference memory. In both species, females exhibited superior working memory during acquisition, and were better able to handle a higher memory load. However, male mice and rats exhibited better reference memory than females during the asymptotic portion of testing. Our data suggest that females may be better at working memory when both working and reference memory information must be learned simultaneously, and males better at reference memory when it has been differentiated from working memory.

Spatial learning, discrimination learning, paw preference and neocortical ectopias in two autoimmune strains of mice

NZB and BXSB mice were given a battery of behavioral tests including paw preference, water escape, Lashley III maze, and discrimination learning. Their brains were then evaluated for cortical ectopias. The incidence of ectopias was 40.5% in NZBs and 48.5% in BXSBs. In the NZB strain left-pawed ectopic mice (both male and female) had the fastest swimming time in the water escape test, while right-pawed ectopics were the slowest. The same findings were obtained for left- and right-pawed ectopic BXSB males, but not for the females. However, on discrimination learning the BXSB males had the exact opposite pattern: right-pawed ectopics were the best learners while left-pawed ectopics were the worst. Male BXSBs and both male and female NZBs were manifesting autoimmune disease at the time of testing, while female BXSBs were not, suggesting that autoimmunity is a necessary background condition for the differential expression of ectopias and paw preference upon learning processes. The finding that the left-pawed ectopic BXSB mice, who were the poorest learners in the non-spatial discrimination learning test, learned best in the spatial water escape test is in agreement with the Geschwind hypothesis that pathological events during brain development may, in some instances, produce superiority of function.