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Biomedical subjects

V H Denenberg

Publications and source records attributed to V H Denenberg.

172 records · Page 10Linked to original sources

Rabbit: frequency of suckling in the pup.

Rabbit does were given free access to their young, access once a day, and access twice a day. In all three groups the young were nursed only once every 24 hours. Growth curves for the pups from day 2 of age to day 30 were identical for all three groups. The restriction of suckling to once a day appears to depend on the mother and not the pups.

Animals↗

Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse.

Biochemical parameters in the brains of olfactory bulbectomized male and female mice were studied in two experiments, followed by three experiments in which 5-HTP was injected into bulbectomized males and females to try to block abnormal behaviors. In Experiment 1 bulbectomized male and female mice had significantly less tryptophan hydroxylase in their brains than did sham controls. Neither 5-hydroxtryptophan decarboxylase nor tyrosine hydroxylase activity was affected. In Experiment 2 the rate of synthesis of 5-HT was significantly less in bulbectomized males and females. Since bulbectomy leads to increased pup killing by female mice, the objective of Experiments 3 and 4 was to see whether the injection of 5-HTP into bulbectomized females could block this behavior. The incidence of pup killing was not influenced, but in both studies the latency to kill was significantly prolonged. Olfactory bulbectomy eliminates aggressive behavior in male mice, and the purpose of Experiment 5 was to determine whether 5-HTP treatment could restore normal levels of aggression. No significant effect was found. The data suggest that a dual mechanism is needed to explain the behavioral abnomalities seen in the two sexes; the mechanism in the female appears to be serotonergic while that in the male is still unknown.

5-Hydroxytryptophan↗

Working memory deficits in BXSB mice with neocortical ectopias.

Approximately 40-60% of BXSB/MpJ-Yaa mice exhibit neocortical ectopias, which are misplaced clusters of neurons in layer I of cortex. These ectopias are usually located in the prefrontal and/or motor region of cortex in BXSB mice, and are similar in appearance to those found in postmortem analyses of the brains of dyslexic humans. Several within-strain learning differences between mice with ectopias and those without have been reported. In particular, ectopic BXSB mice exhibited superior reference memory learning, but inferior working memory learning in several studies from our laboratory. This study used the Morris water maze delayed matching-to sample task and the water radial-arm maze to asses working memory in female BXSB mice with and without ectopias. In the delayed matching-to sample task, a hidden escape platform remained in a constant position for each four-trial session, but changed position between sessions. Trial 2 was the measure of working memory, i.e., how well did the mouse remember where the platform was located for that session. In the water version of the eight-arm radial maze, hidden escape platforms were located in four of the eight arms, and each platform was removed from the maze once found. This enabled us to assess working and reference memory simultaneously. Ectopic mice demonstrated working memory deficits during the first part of the delayed matching-to sample task compared to nonectopics. Similarly, ectopics made more working memory errors during the latter half of radial-arm maze testing, while not differing from nonectopics in reference memory performance. Additionally, there were significant correlations between measures of working memory in the radial-arm maze and working memory in a delayed matching-to-sample task. These findings are in agreement with other studies demonstrating working memory deficits in ectopic BXSB mice.

Animals↗

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.

Animals↗

Neocortical ectopias in BXSB mice: effects upon reference and working memory systems.

BXSB mice have an approximately 40-60% incidence of neocortical ectopias in layer I of the prefrontal/motor cortex. Prior studies have found major behavioral differences between those with ectopias and their non-ectopic littermates. Some of these findings indicate that the two groups differ with respect to spatial reference and working memory. The purpose of this study was to measure reference and working memory in the same animals to test the hypothesis that the ectopics would have better reference memory but less effective working memory. The Lashley III maze has cul-de-sacs which must be eliminated, and T-choices where the animal has to decide whether to go left or right. Ectopic and non-ectopic mice were equally able to learn the maze and did not differ on cul-entry or T-choice errors. Then the maze was inverted and the animals were retested. Turning the maze upside down did not change the relative status of the blind alleys. Therefore, the reference memory knowledge from the prior week's training could be used to avoid entering the culs. However, inverting the maze caused a left-right mirror image reversal of the T-choices. Therefore, prior reference memory information would interfere with learning the new path through the maze, whereas working memory would enable the mouse to eliminate T-choice errors. Ectopic mice made less cul-entry errors and more T-choice errors than their non-ectopic littermates, as predicted.

Animals↗

Varying intertrial interval reveals temporally defined memory deficits and enhancements in NTAN1-deficient mice.

The N-end rule is one ubiquitin-proteolytic pathway that relates the in vivo half-life of a protein to the identity of its N-terminal residue. NTAN1 deamidates N-terminal asparagine to aspartate, which is conjugated to arginine by ATE1. An N-terminal arginine-bearing substrate protein is recognized, ubiquitylated by UBR1/E3alpha, and subsequently degraded by 26S proteasomes. Previous research showed that NTAN1-deficient mice exhibited impaired long-term memory in the Lashley III maze. Therefore, a series of studies, designed to assess the role of NTAN1 in short- and intermediate-term memory processes, was undertaken. Two hundred sixty mice (126 -/-; 134 +/ +) received Lashley III maze training with intertrial intervals ranging from 2-180 min. Results indicated that inactivation of NTAN1 amidase differentially affects short-, intermediate-, and long-term memory.

Amidohydrolases↗

More power to them--statistically, that is: a commentary on Studdert-Kennedy, Mody, and Brady's criticism of a critique.

The power analysis discussed above establishes that it was most unlikely that Mody et al. (1997) could make a meaningful test of the Tallal hypothesis because of inadequate n and failure to specify the effect size. Note that this is a best-case scenario, because the power analysis assumes that the analysis of variance assumptions were within reasonable boundaries (e.g., as specified by Norton's study). This was clearly not the case. In summary, the Mody et al. study fails to meet minimal scientific criteria and makes no meaningful contribution to the literature.

Analysis of Variance↗

A critique of Mody, Studdert-Kennedy, and Brady's "Speech perception deficits in poor readers: auditory processing or phonological coding?".

A 1997 article by Mody, Studdert-Kennedy, and Brady claimed that their studies constituted a critical test of two hypotheses concerning students with reading impairment: (a) that they experience speech-specific failure in phonological representation, and (b) they display general deficits in auditory temporal processing. From these studies, the authors concluded that their findings were consistent with the first hypothesis but were not in agreement with the second. A critical analysis of the Mody et al. article leads to the conclusion that it makes no contribution to that debate because (a) the children in the Poor reading group did not meet the accepted reading-impairment criterion of being delayed by at least 1 year in their reading skills, (b) there were severe violations of statistical assumptions, and (c) their conclusions were based on the failure to find significant differences, thus compelling them to accept the null hypothesis as proven, in the absence of any statistical power analysis.

Auditory Perceptual Disorders↗