Biomedical subjects

H T Blair

Publications and source records attributed to H T Blair.

At least 19 recordsLinked to original sources

PubMed1995

Anticipatory head direction signals in anterior thalamus: evidence for a thalamocortical circuit that integrates angular head motion to compute head direction.

Several regions in the rat brain contain neurons known as head-direction cells, which fire only when the rat's head is facing in a specific direction. Head-direction cells are influenced only by the direction of the head with respect to the static environmental surroundings, and not by the position of the head relative to the body. Each head-direction cell has its own preferred direction of firing, so that together, the population of cells provides a continuous signal of momentary directional heading. Here, head-direction cells were recorded from the post-subicular cortex (PSC) and anterodorsal nucleus (ADN) of the thalamus of freely moving rats. Cell activity was analyzed in relation to both momentary head direction, and the angular velocity of head turns. Head-direction cells in PSC maintained the same directional firing preference, regardless of the angular head velocity. By contrast, head-direction cells in ADN systematically shifted their directional firing preference, as a function of angular head velocity. The ADN cells always shifted their directional tuning peak to the left during clockwise head turns, and to the right during counterclockwise head turns. These results suggest that ADN neurons anticipate the future direction of the head, whereas PSC neurons encode the present direction of the head. Based on these findings, we hypothesize that neurons in PSC and ADN are reciprocally connected to form a thalamocortical circuit, which computes the directional position of the rat's head by integrating the angular motion of the head over time.

Animals↗

PubMed1995

Influences of vestibular and visual motion information on the spatial firing patterns of hippocampal place cells.

Hippocampal place cells show location-specific firing as animals locomote in an environment. A possible explanation for these place fields is that each cell is simply driven by environmental sensory inputs available in its field. This cannot provide the full explanation, however, since cells can maintain stable place fields even in the absence of reliable environmental orienting cues. This suggests the cells are also influenced by movement-related information, since this is the only available, ongoing indicator of current location when external orienting cues are not present. Two candidates for the movement-related information are vestibular activation, and visual motion. To test for these influences, place cells were recorded as animals locomoted in a cylindrical apparatus that was made so that its wall (painted with vertical black and white stripes) and floor could be independently rotated, to provide visual motion and vestibular inputs, respectively. The results showed that both these inputs could influence place fields. Sometimes they caused a predictable locational shift, so that the field rotated its location on the apparatus floor in a way that was compatible with the movement indicated by the vestibular and/or visual motion input. This updating was most reliably obtained when the two inputs were presented in combination. In other cases, the apparatus rotations caused unpredictable changes in firing characteristics, so that cells either stopped firing, or developed place fields that were altered in overall size, shape, and eccentricity. Interestingly, the probability of these changes increased with experience with the rotational manipulations, suggesting a learned component.

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PubMed1994

Influence of fetal and maternal genotype for circulating insulin-like growth factor I on fetal growth in mice.

The role of insulin-like growth factor I in the regulation of fetal growth was investigated in two lines of mice selected for high or low concentrations of this factor in plasma. In Expt 1, females from each line were mated with males of the reciprocal line to generate fetuses of equivalent genotype. Females with low concentration of the factor in plasma exhibited the typical negative relationship between mean fetal mass and litter size (b = -0.032 +/- 0.006 g per fetus, P < 0.01). However, dams of the line with high concentrations of the factor did not exhibit this relationship (b = -0.004 +/- 0.006 g per fetus), despite the fact that they had 26% larger litters (P < 0.05) at a common maternal body mass. This difference in maternal constraint apparently reflects a greater capacity for nutrient transfer to the fetuses in the dams with more insulin-like growth factor I in plasma, as suggested by the absence of a relationship between mean placental mass and mean fetal mass in that line. In Expt 2, the effect of fetal genotype for insulin-like growth factor I was investigated by transferring embryos of the two lines into females of an unrelated strain. Fetuses from the line with high concentrations of the factor in plasma were heavier at term (1.51 versus 1.37 g, pooled SE = 0.05 g, P < 0.05) than fetuses from the line with low concentrations in plasma. It is therefore concluded that fetal growth is influenced by both the maternal and fetal genotypes for insulin-like growth factor I, but in qualitatively different manners.

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PubMed1993

Stimulus configuration, spatial learning, and hippocampal function.

Schmajuk and DiCarlo (Psychol. Rev., 99 (1992) 268-305) introduced a neural network, which utilizes a biologically plausible backpropagation procedure, to describe configural paradigms in classical conditioning. The model correctly describes many experimental results under the assumption that aspiration lesions of the hippocampus eliminate (a) the competition between simple and configural stimuli to gain association with the unconditioned stimulus and (b) the adjustment of initially random configural stimuli. The present study extends the network to describe place learning. Under the assumption that ibotenic acid lesions of the hippocampus only impair the adjustment of initially random configural stimuli, the model correctly shows that ibotenic acid lesions might spare a configural discrimination but impair place learning. In general, the results are taken to support a hippocampal role in the modulation of stimulus configuration.

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PubMed1993

Maps, routes, and the hippocampus: a neural network approach.

This study describes hippocampal participation in maze navigation in terms of a real-time, biologically plausible neural network. The system is composed of (1) a goal-seeking mechanism, (2) a cognitive map system, and (3) a route system. The goal-seeking mechanism displays exploratory behavior until either the goal is found or a sufficiently strong prediction of the goal is generated. The cognitive map is a topological map that stores associations between places and views of accessible places, and between places and reward. The route system establishes associations between cues and reward. Both systems compete with each other to establish associations with the reward, with the cognitive system generally overshadowing the route system. In agreement with previous models, it is assumed that the hippocampus modulates the storage of cognitive maps in cortical areas and mediates the competition between cognitive maps and route systems. After hippocampal lesions, animals navigate through mazes making use of the route system. Computer simulations show that the network effectively describes latent learning, detour behavior, and place learning in normal and hippocampal- and cortical-lesioned animals.

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PubMed1992

Body growth, carcass composition, and endocrine changes in lambs chronically treated with recombinantly derived insulin-like growth factor-I.

Castrate yearling male sheep were treated for 8 weeks with either 50 micrograms/kg body wt/8 hourly sc insulin-like growth factor-I (IGF-I) (n = 10) or with saline (n = 9). IGF-I treatment increased plasma IGF-I from 235 +/- 17 to 347 +/- 16 ng/ml (P less than 0.001). There was a gradual divergence in body wt (P less than 0.10) between treatment groups. Food intake did not change significantly. The weight of the spleen corrected for body wt increased by 40% (P less than 0.001) and there was a marginal increase in adjusted kidney wt (P less than 0.1). There was no effect of IGF-I on carcass weight or dimensions, or on long bone length, although the weight per unit length of the tibia (P less than 0.05) and femur (P less than 0.10) were increased. There was no effect on wool growth. Plasma IGF binding proteins (IGFBPs) were quantified by ligand blot analysis. In the IGF-I treated group, IGFBP-1 showed a transient increase (P less than 0.05) at day 3 but was similar in both groups at day 55 of treatment. IGFBP-2 was suppressed (P less than 0.05) by day 55 and IGFBP-3 and 4 did not change. Plasma glucose was elevated (P less than 0.05) and plasma insulin was suppressed (P less than 0.01) from 280 +/- 32 pg/ml to 124 +/- 30.4 pg/ml, plasma urea (P less than 0.01) and creatinine (P less than 0.05) were reduced in the IGF-I treated group. The somatogenic effect of IGF-I in this study was minimal suggesting that in the well fed animal with an intact somatotropic axis IGF-I treatment at doses which double plasma IGF-I does not enhance somatic growth performance. However, the marked splenomegaly shows the sensitivity of splenic growth to systemic IGF-I. The suppression of insulin with chronic IGF-I treatment was accompanied by hyperglycaemia--this may explain in part the lack of a significant anabolic response and may limit the utility of IGF-I therapy unless higher doses with insulin-like effects are used.

Aging↗

PubMed1992

The interrelationship between and the regulation of hepatic growth hormone receptors and circulating GH binding protein in the pig.

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p less than 0.001) and [125I]bGH binding to hepatic membranes (p less than 0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8 +/- 1.2 (mean +/- 1 x SEM) (controls) to 17.8 +/- 2.0% in infants, and from 35.2 +/- 2.6 (controls) to 41.8 +/- 3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p less than 0.05), from 7.0 +/- 1.6 (controls) to 15.4 +/- 3.6% in infants and from 53.7 +/- 7.1 (controls) to 65.1 +/- 11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r = 0.82, p less than 0.001), with a correlation of r = 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r = 0.13). Serum IGF-I correlated significantly with serum GH BP (r = 0.93, p less than 0.001) and [125I]bGH membrane binding capacity (r = 0.91, p less than 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1992

Effects of season and testosterone treatment on gonadotrophin secretion and pituitary responsiveness to gonadotrophin-releasing hormone in castrated Romney and Poll Dorset rams.

In castrated rams (Romney and Poll Dorset, n = 8 for each breed), inhibition by testosterone treatment (administered via Silastic capsules) of luteinizing hormone (LH) pulse frequency, basal and mean LH concentrations, mean follicle-stimulating hormone (FSH) concentration, and the peak and total LH responses to exogenous gonadotrophin-releasing hormone (GnRH) were significantly (P less than 0.01) greater during the nonbreeding than during the breeding season. Poll Dorset rams were less sensitive to testosterone treatment than Romney rams. In rams not receiving testosterone treatment, LH pulse frequency was significantly (P less than 0.05) lower during the nonbreeding season than during the breeding season in the Romneys (15.8 +/- 0.9 versus 12.0 +/- 0.4 pulses in 8 h), but not in the Poll Dorsets (13.6 +/- 1.2 versus 12.8 +/- 0.8 pulses in 8 h). It is concluded that, in rams, season influences gonadotrophin secretion through a steroid-independent effect (directly on hypothalamic GnRH secretion) and a steroid-dependent effect (indirectly on the sensitivity of the hypothalamo-pituitary axis to the negative feedback of testosterone). The magnitude of these effects appears to be related to the seasonality of the breed.

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PubMed1992

Elevating maternal insulin-like growth factor-I in mice and rats alters the pattern of fetal growth by removing maternal constraint.

Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P less than 0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I (10 micrograms 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1992

Growth allometry of organs, muscles and bones in mice from lines divergently selected on the basis of plasma insulin-like growth factor-I.

Growth allometry was examined over the range 6 to 112 days of age in male and female mice from lines selected for low (L) or high (H) plasma concentrations of insulin-like growth factor-I (IGF-I). Plasma IGF-I concentrations were greater in the H line than in L line mice from 28 days of age. H line mice also had greater liveweights and weights of the heart, kidneys, pancreas, lungs, liver, brain and testes from 21-28 days of age. Changes in weights of these organs reflected the general pattern of body growth, there being no consistent effects of selection line on allometric growth coefficients. Ovarian weights were not different between the lines. For muscle weights, (gastrocnemius, quadriceps femoris), the weights or lengths of bones (tibia, femur) and the nose-anus and anus-tail lengths, allometric growth coefficients were generally higher (P less than .05) in L line females than in L line males or H line mice of either sex. The allometric growth coefficient for spleen was significantly (P less than .05) greater in H line mice than in L line mice with the result that spleen weights were 30% higher in H line mice from 28 days of age. This is consistent with results from mice treated with, or transgenic for, IGF-I and suggests a specific effect of this hormone on growth of the spleen. Thymus weights were also greater in H line than in L line mice and developmental patterns of thymus weight closely paralleled those of circulating IGF-I.

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PubMed1990

Developmental patterns of plasma insulin-like growth factor-1 concentrations in sheep.

A study was undertaken to examine the ontogeny of circulating insulin-like growth factor-1 (IGF-1) concentrations in sheep. The trial was a balanced 2 x 2 factorial design incorporating the effects of sex and rearing rank with a total of 48 animals. Blood sampling was initiated four weeks post-weaning (about 3 months of age) and continued every 2 weeks for 6 months and then every 4 weeks for 7 months. Fecal egg counts and plasma concentrations of non-esterified fatty acids (NEFA) were also determined. IGF-1 concentration was positively related to live weight throughout the trial, even when adjusted to common sex and rearing rank. Sex of lamb had a significant effect on plasma IGF-1 concentrations with concentrations in males being greater than those in females. Puberty in females, as determined by date of first estrus, was associated with an increase in plasma IGF-1 concentrations. Although puberty in males was not measured, a surge in plasma IGF-1 concentrations around the approximate time of puberty in males resulted in a marked divergence between the sexes which remained throughout the study. Rearing rank did not influence plasma IGF-1 concentrations beyond 7 months of age. Plasma IGF-1 concentrations tended to be negatively associated with plasma NEFA concentrations and fecal egg counts but relationships were only occasionally significant. IGF-1 levels were highly repeatable, concentrations at the first sample being significantly correlated with those at all subsequent samples. Implications of these results in relation to potential use of plasma IGF-1 concentration as a genetic marker for productivity are discussed.

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PubMed1990

Developmental patterns of plasma insulin-like growth factor-I (IGF-I) and body growth in mice from lines divergently selected on the basis of plasma IGF-I.

A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P less than 0.05) but not by sex. Significant (P less than 0.001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P less than 0.001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1989

Responses to divergent selection for plasma concentrations of insulin-like growth factor-1 in mice.

A divergent selection experiment with mice, using plasma concentrations of insulin-like growth factor-1 (IGF-1) at 42 days of age as the selection criterion, was undertaken for 7 generations. Lines were not replicated. To obtain sufficient plasma for the IGF-1 assay, blood from four individuals was volumetrically bulked to obtain a litter mean IGF-1 concentration. This necessitated the use of between family selection. Although inbreeding accumulated in a linear fashion in each of the high, control and low lines, the rates were different for each line (3.6, 1.6 and 5.3% per generation for the high, control and low lines, respectively). As a consequence, the effects of selection and inbreeding are confounded in this experiment. Divergence between the high and low lines in plasma concentrations of IGF-1 continued steadily until generation 5. In generations 6 and 7, there was a reduced degree of divergence and this contributed towards the low realized heritability value of 0.15 +/- 0.12. Six-week liveweight showed a steady positive correlated response to selection for or against plasma concentrations of IGF-1 until generation 4 (high-low difference = 1.7 g = 12%). In generation 5, a substantial drop in 6-week liveweight in the low line relative to both the high and control lines occurred (high-low difference, 3.9; g, 25%). This difference was maintained until generation 7.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1989

Role of testosterone in regulating the growth of mice from lines selected for low vs high plasma insulin-like growth factor-I concentrations.

A study was undertaken to investigate the role of testosterone in regulating growth and circulating levels of insulin-like growth factor-I in male mice from lines divergently selected on the basis of plasma IGF-I. Controls of each lines were sham-operated at 10 days of age and treated with peanut oil from day 14 to day 70. A second group, which was castrated at 10 days and treated with testosterone enanthate (0.5 micrograms.(g body weight)-1.day-1) from day 14 to 70, did not differ from controls in body weight but had higher plasma IGF-I concentrations. Delaying testosterone therapy until day 42 in a third group retarded growth, with body weights being significantly lower than those of other two groups from days 35 to 56. However, plasma IGF-I levels in this group were not different from those of controls. Effects of line and treatment were additive. It is concluded that the greater pubertal growth of high-line compared to low-line males is not due to greater stimulation of circulating IGF-I by testosterone. Furthermore, testosterone does not appear to influence pubertal growth by acting on circulating levels of IGF-I.

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PubMed1989

Reproductive performance and fetal growth in female mice from lines divergently selected on the basis of plasma IGF-1 concentrations.

Reproductive performance, mammary gland weight and plasma concentrations of insulin-like growth factor-1 (IGF-1) were examined in 18-day-pregnant mice from lines divergently selected on the basis of plasma IGF-1 concentration. Females of the high IGF-1 (H) line were 14% heavier than those of the low IGF-1 (L) line at mating but did not differ in conception rate during a 15-day mating period. H-line females produced significantly larger litters by an average of 1.5 fetuses (19%), heavier fetuses (7%), greater total fetal weight (30%), heavier placental discs (15%), greater total placental weight (35%) and heavier mammary glands (18%). Plasma IGF-1 values were 12% greater in H-line than L-line females at Day 19 of gestation but the line difference was not significant. It is concluded that differences between the lines in litter size and mammary gland weight are most likely due to differences in maternal bodyweight (which are in turn a consequence of selection for plasma IGF-1 at puberty). Whether the difference in fetal weight is a function of fetal capacity to grow in utero or ability of the dam to provide nutrients for fetal growth is yet to be determined.

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PubMed1989

Somatotrophic receptors in hepatic tissue of the developing male pig.

The development of hepatic somatotrophic receptors and plasma concentrations of insulin-like growth factor-I (IGF-I) were investigated at five different ages (2, 20, 35, 105 and 165 days) in four male pigs per group. The specific binding of 125I-labelled porcine GH (pGH) to hepatic somatotrophic membranes was very low at 2 days of age (0.53 +/- 0.12%), and increased progressively (P less than 0.01) with advancing age to 3.60 +/- 0.95% at 165 days of age. Specific binding of 125I-labelled bovine GH (bGH) to the same membrane preparations was markedly higher than binding of 125I-labelled pGH; it also showed a distinct developmental increase (P less than 0.01) with age from 4.4 +/- 0.55% at 2 days of age to 24.0 +/- 1.90% at 165 days of age. Plasma concentrations of IGF-I increased significantly (P less than 0.01) from 79 +/- 14.0 micrograms/l at 2 days of age to 610 +/- 64.0 micrograms/l at 165 days of age. Non-linear regression analysis of the competitive binding data using bGH as labelled and unlabelled ligands showed linear Scatchard plots in the three youngest age groups, with an association constant (Ka) of approximately 3.5 litres/nmol. Curvilinear Scatchard plots were observed in the two oldest age groups. The Ka for the higher affinity binding site (approximately 5.0 litres/nmol) was very similar to that for the sole site observed in the younger animals. The Ka of the lower affinity binding site was approximately 0.35 litres/nmol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Genetic selection for insulin-like growth factor-1 in growing mice is associated with altered growth.

Substantial responses in the 6-week and mature body-weights of mice occurred after 7 generations of selection for or against plasma levels of Insulin-like Growth Factor-1 (IGF-1). Plasma levels of IGF-1 were also significantly different after 7 generations of selection (high line = 85 +/- 2 ng/ml, low line = 58 +/- 2 ng/ml). The average 6-week weight in the line selected for high plasma IGF-1 was 22.5 +/- .2 g compared with 18.5 +/- .2 g in the low plasma IGF-1 line, after 7 generations of selection. The difference between lines was maintained at 20 weeks of age. These data provide further evidence for the roles of IGF-1 in the regulation of somatic growth and as a mediator of a genetic component of growth.

Aging↗

PubMed1987

Variation in plasma concentration of insulin-like growth factor-1 and its covariation with liveweight in mice.

Three experiments were undertaken to examine the degree and causes of variation in plasma concentrations of insulin-like growth factor-1 (IGF-1) in mice. The relationship between IGF-1 concentrations and liveweight was also examined. In all three experiments, a number of non-genetic factors were found to contribute significantly to the variation in IGF-1 concentrations, the most important of these being sex and litter size. In one experiment, where pups from 16 litters were cross-fostered to avoid the confounding of maternal and direct genetic effects, a heritability of 0.40 +/- 0.27 was estimated for plasma IGF-1 concentration at 35 days of age. To examine further the existence of genetic variation in plasma concentrations of IGF-1 and the genetic covariation between plasma IGF-1 levels and other body traits, a selection experiment with mice has been initiated. Moderate to strong phenotypic correlations between IGF-1 concentrations and weight at an early age have been found in all three experiments.

Aging↗