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Biomedical subjects

V H Denenberg

Publications and source records attributed to V H Denenberg.

At least 91 records · Page 5Linked to original sources

Neurochemical asymmetries in the albino rat's cortex, striatum, and nucleus accumbens.

The concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the right and left cortex, striatum, and nucleus accumbens of adult Purdue-Wistar rats. There was more DA in the right cortex and accumbens and a greater concentration of NE in the left striatum. There is more 5-HT in the left striatum and right accumbens, more 5-HIAA in the left cortex, as well as a greater 5-HT turnover in the left accumbens. These results are considered in the light of previous findings concerning the relationship of neurochemical asymmetries and behavioral lateralization.

3,4-Dihydroxyphenylacetic Acid↗

Some statistical and experimental considerations in the use of the analysis-of-variance procedure.

Researchers often test the wrong statistical hypothesis in evaluating their experiments, thereby drawing wrong conclusions. Examples of this are given. In addition, data containing correlations among subjects require a different form of statistical analysis than do data involving independent observations. Errors that can result from an incorrect analysis are illustrated.

Analysis of Variance↗

Lateralization of spatial preference in the female rat.

Female rat pups were either left undisturbed in infancy and raised in lab cages or were handled in infancy and raised in enriched environments. In adulthood, animals underwent brain surgery consisting of: 1) a right neocortical ablation, 2) a left neocortical ablation, 3) a sham operation, or 4) no surgery. After recovering, they were tested for the initial direction of movement (left or right) in the open field. Nonhandled intact females were biased to move leftward indicating an asymmetrical brain organization. The intact handled-enriched group was unbiased. The right and left lesions caused the animals to move ipsilateral to the lesion, but there was no difference in the magnitude or response in either early experience group. Thus, early experience in the female rat has a different effect then in the male, and the nature of the brain organization in the two sexes is markedly different.

Animals↗

Comparisons of behavioral, motoric and electrical criteria for assessment of sleep-wake states in the rabbit.

Each of the sleep and wake states of animals are characterized by specific patterns of behavioral, motoric, and electrophysiological activity. The purpose of this study was to determine the amount of agreement among these three patterns. Sleep-wake behavior of two adult rabbits was observed for 4 continuous hours by an experienced judge. At the same time, a single-channel analog recording of motility and an analog recording of the electrical activity of the hippocampus were obtained. Each recording was scored by assigning a state category to each 10-second epoch. The three descriptions were then compared for agreement using the 10-second epoch as the unit of statistical analysis. There was a mean agreement of 85.12% between the techniques of direct observation and judgment of motility recordings. A mean agreement of 95.64% was obtained when comparing the hippocampal recordings and those of direct observation; the hippocampal and motility recordings had a mean agreement of 85.38%. The high correlations among the three different procedures support the hypothesis that state is a construct representing a set of underlying neurophysiological properties of the organism which express themselves in a similar and invariant manner via behavior, motility, and electrical brain activity.

Animals↗

Prenatal testosterone causes shift of asymmetry in neonatal tail posture of the rat.

Neonatal tail posture is a sexually dimorphic behavior with females more biased leftwards than males. Prenatal exposure of female pups to testosterone propionate (TP) but not dihydrotestosterone propionate (DHTP) shifts the population pattern of tail posture to the right. No effects were found with male pups. Since TP is aromatizable and DHTP is not, it is concluded that TP exerts its effects on tail posture via the CNS.

Animals↗

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.

Aggression↗

Interhemispheric coupling coefficients: sex differences in brain neurochemistry.

Previously it was shown that the presence of a significant positive correlation between measures of the right and left hemispheres may be taken as evidence of a negative feedback loop linking the hemispheres [Denenberg, V. H. Am. J. Physiol. 238 (Regulatory Integrative Comp. Physiol. 7): R3-R13, 1980]. Such a finding is indicative of a different form of brain organization, compared with brains that lack this correlation. The purpose of this paper was to compare male and female rats with respect to correlations of left- and right-sided values for a set of brain neurochemicals. The variable of sex was chosen because there are ample data showing differences in brain organization. Neurochemical correlations in the nucleus accumbens and the striatum did not demonstrate any sex difference, but differences were found in neocortex: female rats had significantly greater hemispheric correlations than males for dopamine, 5-hydroxyindoleacetic acid, and serotonin turnover.

Animals↗

Lateralization of function in rats.

Research findings during the past several years have shown that the rat's brain is lateralized for a number of behavioral functions. Neurochemical and anatomical asymmetries have also been found and, in some instances, have been associated with the behavioral asymmetries. It has also been found that extra stimulation in early life can enhance existing asymmetries or can induce asymmetries where none previously existed.

Aggression↗

Effects of theophylline on behavioral state development in the newborn rabbit.

On Day 1 of life (Day 0 = birth), the sleep-wake behavioral states of rabbits were measured for 2 hr, after which half the animals received 10 mg/kg of theophylline by intubation (N = 16), whereas the remainder received normal saline (N = 17). Behavioral states were then measured on Days 2, 3, 5, 7, 15, 20, 30 and 40. Theophylline sharply reduced active sleep starting on Day 2 and continuing through Day 20. The development of quiet sleep was delayed for 10 days in the drug-treated group. Paralleling the loss of active sleep was a major increase in wake between Days 2 to 20. The drug also affected the intermediate states of sleep-wake transition and active-quiet sleep transition. The data raise major questions about the safety of a drug widely used in the newborn intensive care setting.

Aging↗

Stimulation in infancy facilitates interhemispheric communication in the rabbit.

Experimental rabbits were stimulated in infancy by being handled, while controls were undisturbed. After reaching adulthood, the animals were tested for activity in an open field with: (i) the right eye occluded; (ii) the left eye occluded; and (iii) neither eye occluded. For rabbits not stimulated in infancy, the correlation between activity scores for the left eye and right eye occlusion conditions was not significant (r = 0.115). In contrast, the correlation was highly significant for handled animals (r = 0.829). The results of the nonhandled group are consistent with other research which has failed to find interocular transfer of visual information, while the significant interhemispheric correlations within the handled group are consistent with prior findings obtained with rats. The results suggest that stimulation in infancy may act to facilitate the functional competence of the corpus callosum.

Animals↗

State organization in neonates: developmental inconsistency indicates risk for developmental dysfunction.

Twenty-two healthy full-term infants were observed for 7 continuous hours in their homes weekly on weeks 2, 3, 4, and 5. Code recordings of their behavioral states and any mother-infant interactions were made every 10 seconds. An analysis was made of the distribution of the infant's state behaviors during the time it was left alone (mean = 279.6 minutes in 7 hours). The states were Waking Active, Quiet Alert, Fuss or Cry, Drowse or Transition, Active Sleep, and Quiet Sleep. Four state profiles were obtained for each infant, one for each week of observation; then a single quantitative measure of profile consistency over weeks was calculated. Infants with the four lowest profile consistency indices had major developmental problems between 3.5 and 30 months (p less than .001): one had aplastic anemia; a second had hypsarrhythmia, a third died of SIDS, and the fourth was hyperactive, both at home and in a testing situation. Other infants with low consistency scores showed minor developmental delays at 6 months and at 30 months. None of the infants at the upper end of the consistency continuum showed evidence of any developmental dysfunction by 30 months of age. The findings indicate that developmental inconsistency in state organization during the neonatal period is predictive of risk for later development.

Child Behavior↗

Cross-species invariance in state-related motility patterns.

Each of the sleep and wake states of animals are characterized by specific patterns of behavioral, motoric, and electrophysiological activity. Sleep-wake behavior of rats, rabbits, and human infants (3 of each species) was observed, and, at the same time, a single-channel analog recording was obtained of the motoric activity. A judge who had extensive experience in observing sleep-wake behaviors of human infants, but who was unfamiliar with these behaviors in nonhuman species, scored the analog signals of the rats and rabbits. Another judge, who knew rat and rabbit state behaviors well, but who had not had experience observing human infants, judged the states of the human infants from the analog signals. These judgments were evaluated by comparing them with the findings obtained from direct observation of the subjects. For the nine subjects, the correlations between the judges' scoring of the analog recording and direct observation ranged from 0.856 to 0.985. A more stringent criterion is to determine the exact agreement between judge and observer for each 10-s epoch during the observation. For the major states of active sleep and quiet sleep, the exact agreement ranged from 95.2 to 100%. The wake state was easily judged for rats (100% agreement) but was more difficult for rabbits and humans (59.9 and 66.7%, respectively). This ability to accurately score the state behavior of an unfamiliar species from an analog movement record alone represents a cross-species invariance in neuromotor organization. The critical parameters appear to be regularity or irregularity of respiration and the temporal distribution of gross motor movement.

Aging↗

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.

Arousal↗

Handling in infancy, taste aversion, and brain laterality in rats.

Rats were handled for the first 20 days of life or were not disturbed. When adults, they were trained to approach and drink from a bottle containing sweetened milk and were then given an injection of lithium chloride to induce a taste aversion conditioned emotional response. Others were injected with physiological saline. Rats within each of the treatment groups were then randomly assigned to 4 surgical procedures: removal of the right or left neocortex; sham surgery; or no surgery. Postoperatively, they were tested for retention of taste aversion by presenting the sweetened milk and recording the amount consumed. The initial consummatory behavior was very low (showing retention of the aversion) and increased over time. There were no differences in the reacquisition curves of the non-handled groups which had received lithium chloride. The curves of the handled groups did differ: thos with an intact right hemisphere (left neocortical lesion) had the lowest asymptote, followed by the group with an intact left brain, while those with intact whole brains consumed the greatest amount of milk. In the groups given an injection of physiological saline, those with a left hemisphere lesion consumed less milk than the other groups, regardless of their early handling experience. The data show: (1) that the rat's brain is lateralized, with the right hemisphere being preferentially involved in conditioned emotional behavior; and (2) that handling in infancy makes the left hemisphere less suceptible to conditioned fear.

Animals↗

Brain and behavioral asymmetries for spatial preference in rats.

Rats were handled daily for 3 min between birth and weaning, or were nonhandled controls. When adult, 4 males from each litter received a right neocortical ablation, a left ablation, a sham operation, or no surgery. A month later all animals were tested in the open field for 4 days, and their initial direction of movement from the starting square (whether right or left) was recorded. Non-handled rats with intact brains (sham-operated and no-surgery groups pooled) had a mean directionality score near zero, thus indicating no right-left spatial preference. However, non-handled animals without a left hemisphere were significantly more biased in going to the ipsilateral side than were their siblings with right-brain ablations. Thus, in non-handled animals behavioral symmetry in making spatial choices is due to balanced brain asymmetry, in which the right hemisphere biases the animal to move leftward while the left hemisphere acts to inhibit this response. In contrast, intact handled rats had a significant preference to go to the left, thus suggesting that in handled animals the right hemisphere controls spatial preference.

Animals↗

General systems theory, brain organization, and early experiences.

Three hypothetical brain processes--interhemispheric coupling, hemispheric activation, and interhemispheric inhibition--are derived from an equation characterizing general systems theory. To investigate these processes, experimental rats were reared under differing early experience conditions. When adult, they had their right or left neocortex lesioned, had a sham operation, or were left undisturbed. Interhemispheric coupling was measured by means of a correlation coefficient between the right and left hemispheres. The presence of a significant positive correlation is taken as evidence of a negative feedback loop between the hemispheres. In one experimental population, in which rats did not receive any extra stimulation in infancy, the correlation was not significantly different from zero, thus implying that the two hemispheres were operating independently. In another population, in which rats had received handling stimulation in infancy, the correlation coefficient was significant (0.543), indicating that the hemispheres were coupled in a systems arrangement. The processes of hemispheric activation and interhemispheric inhibition were assessed by comparing the mean performance of the two unilateral lesion groups and the group with intact brain. The two rat populations had different forms of brain organizations as measured by these processes. These analyses show that the behavior of the isolated hemisphere cannot be directly extrapolated to the behavior of the connected hemisphere. If there is hemispheric coupling via a negative feedback loop or if there is interhemispheric inhibition, then the disconnected hemisphere may show behaviors that are not evident in the normal connected condition.

Brain↗