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Biomedical subjects

R J Nelson

Publications and source records attributed to R J Nelson.

At least 127 records · Page 7Linked to original sources
PubMed1996

High-frequency vibratory sensitive neurons in monkey primary somatosensory cortex: entrained and nonentrained responses to vibration during the performance of vibratory-cued hand movements.

The activity of high-frequency vibratory sensitive (HFVS) neurons was recorded in monkey primary somatosensory cortex (SI) while animals performed wrist flexions and extensions in response to 57-Hz or 127-Hz palmar vibration. HFVS neurons were distinguished by their exquisite responsiveness to the higher frequency vibration (127 Hz). These neurons probably received input from Pacinian afferents. Systematic selection of HFVS neurons was made using K-means cluster analysis of neuronal firing rates during stimulating at 127 Hz and 57 Hz. HFVS neurons constituted approximately 4% of all recorded cells and more frequently were found in areas 3b, 1, and 2 (approximately 5% of total in each area) than in area 3a (approximately 1%). Using circular-statistics analyses for nonuniformity of discharges over the vibratory cycle, HFVS neurons were split into two groups of vibration-entrained neurons (E1 and E2 neurons) and one group of nonentrained neurons (NE neurons). E1 neurons were entrained to vibration at both 127 Hz and 57 Hz, whereas E2 neurons were entrained only at one of these vibratory frequencies. Vibration-entrained neurons often exhibited multimodal distributions of interspike intervals (ISIs), with the modes at multiples of the period of vibration. In addition, for these neurons, ISI clusters in joint interval plots commonly had diagonal orientations that were indicative of negative serial correlations of the ISIs, a feature of extrinsically driven rhythmic activity. HFVS neurons located in areas 3a, 3b, and 1 responded to vibration onset at shorter latencies (16.5 +/- 1.6, 19.8 +/- 5.9, and 21.4 +/- 6.4 ms, respectively, during 127-Hz stimulation) than those located in area 2 (35.6 +/- 13.8 ms). These observations are consistent with a scheme in which HFVS area 2 neurons receive their inputs from more anterior areas of SI. Moreover, entrained neurons exhibited shorter response latencies than nonentrained neurons. During 127-Hz stimulation, response latencies were 17.3 +/- 3.0, 17.5 +/- 2.6, and 25.7 +/- 6.4 ms for E1, E2, and NE neurons, respectively, located in areas 3a, 3b, and 1. Thus, entrained and nonentrained HFVS neurons may belong to different hierarchical stages of information processing.

Analysis of Variance↗
PubMed1996

Characterization of sensorimotor performance, reproductive and aggressive behaviors in segmental trisomic 16 (Ts65Dn) mice.

In the present study, segmental trisomy 16 (Ts65Dn) mice, an animal model of Down Syndrome (DS), were examined for sensorimotor, reproductive, and aggression abnormalities associated with DS. The Ts65Dn mice exhibited no sensorimotor deficits in olfactory sensitivity, visual abilities, orientation reactions, forelimb strength, postural skills, balance/ coordination, climbing, or locomotion compared to genetically matched control B6EiC3HF1 mice. In mating tests, the percentage of Ts65Dn mice displaying intromissions when paired with estrous females was significantly less than that in controls. Although the percentage of Ts65Dn mice that mounted and ejaculated with an estrous female was marginally less than in controls, there were no significant differences on the other measures of reproductive behavioral performance. In aggression tests, Ts65Dn males showed increased offensive aggression in a neutral arena both when paired and among grouped males. Conversely, Ts65Dn mice exhibited less offensive aggression against an intruder in their home cage than control males. In sum, these mice possess some of the adaptive behavior abnormalities observed in DS patients; however, because the Ts65Dn mice do not have any observed sensorimotor deficits that could interfere with behavioral assessments, they may serve as a useful model for the study of behavioral impairments associated with DS.

Aggression↗
PubMed1996

Spatial memory deficits in segmental trisomic Ts65Dn mice.

Spatial memory was assessed in the segmental trisomic 16 mouse (Ts65Dn), a potential model for Down syndrome (DS), using the 12-arm radial maze (RAM). Ts65Dn mice have a portion of mouse chromosome 16 syntenic to the distal end of human chromosome 21 triplicated. On each of 8 daily trials of the RAM, Ts65Dn mice made fewer correct choices than control mice and performed at or near chance levels, indicating a deficit in spatial working memory. On trials 9 and 10, Ts65Dn mice performed as well as control mice on the initial 12 choices, but required a greater number of choices to complete the RAM. The improved performance of Ts65Dn mice on trials 9 and 10 was lost when the animals were retested after a 50-day retention period, suggesting that long-term memory is also defective. These results are not likely explained by differences in either response bias or perceptual discrimination. Ts65Dn and control mice displayed comparable levels of performance in spontaneous alternation in a T-maze, demonstrating that simple spatial memory was not impaired. In the elevated plus maze, Ts65Dn mice did not display higher anxiety levels which could affect their performance in the RAM. In fact, Ts65Dn mice visited open arms on the elevated plus maze more frequently and spent more time on open arms than did control mice. Taken together, these results provide evidence for short- and long-term spatial memory deficits in Ts65Dn mice.

Animals↗
PubMed1996

Interactions between motor commands and somatic perception in sensorimotor cortex.

For many years, it has been postulated that interactions between motor commands and somatic perception in the sensorimotor cortices exist, but they have been difficult to demonstrate. Recent studies have made demonstration of this interaction easier and suggest that cortical activity related to somatic sensation and perception is modified by movement-generating mechanisms. Corollary discharge and efference copy may also play a role in motor behavior.

Animals↗
PubMed1996

Seasonal changes in immune function.

Winter is energetically demanding. Physiological and behavioral adaptations have evolved among nontropical animals to cope with winter because thermoregulatory demands increase when food availability decreases. Seasonal breeding is central within the suite of winter adaptations among small animals. Presumably, reproductive inhibition during winter conserves energy at a time when the adds of producing viable young are low. In addition to the well-studied seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many populations of mammals and birds in the field. Challenging winter conditions, such as low ambient temperatures and decreased food availability, can directly induce death via hypothermia, starvation or shock. In some cases, survival in demanding winter conditions puts individuals under great physiological stress, defined here as an adaptive process that results in elevated blood levels of glucocorticoids. The stress of coping with energetically demanding conditions can also indirectly cause illness and death by compromising immune function. Presumably, the increased blood concentrations of adrenocortical steroids in response to winter stressors compromise immune function and accelerate catabolic mechanisms in the field, although the physiological effects of elevated glucocorticoids induced by artificial stressors have been investigated primarily in the laboratory. However, recurrent environmental stressors could reduce survival if they evoke persistent glucocorticoid secretion. The working hypothesis of this article is that mechanisms have evolved in some animals to combat seasonal stress-induced immunocompromise as a temporal adaptation to promote survival. Furthermore, we hypothesize that mechanisms have evolved that allow individuals to anticipate periods of immunologically challenging conditions, and to cope with these seasonal health-threatening conditions. The primary environmental cue that permits physiological anticipation of season is the daily photoperiod; however, other environmental factors may interact with photoperiod to affect immune function and disease processes. The evidence for seasonal fluctuations in lymphatic organ size, structure, immune function, and disease processes, and their possible interactions with recurrent environmental stressors, is reviewed. Seasonal peaks of lymphatic organ size and structure generally occur in late autumn or early winter and seasonal minima are observed prior to the onset of breeding. Although many of the field data suggest that immune function and disease processes are also enhanced during the winter, the opposite seasonal pattern is also observed in some studies. We propose that compromised immune function may be observed in some populations during particularly harsh winters when stressors override the enhancement of immune function evoked by short day lengths. Because so many factors covary in field studies, assessment of our proposal that photoperiod mediates seasonal changes in immune function requires laboratory studies in which only photoperiod is varied. A review of the effects of photoperiod on immune function in laboratory studies reveals that exposure to short day lengths enhances immune function in every species examined. Short day exposure in small mammals causes reproductive inhibition and concomitant reduction in plasma levels of prolactin and steroid hormones, as well as alterations in the temporal pattern of pineal melatonin secretion. These hormones affect immune function, and influence the development of opportunistic diseases, including cancer: however, it appears that either prolactin or melatonin secretion is responsible for mediating the effects of photoperiod on immune function. Taken together, day length appears to affect immune function in many species, including animals that typically do not exhibit reproductive responsiveness to day length.

Adaptation, Physiological↗
PubMed1996

Photoperiod and population density interact to affect reproductive and immune function in male prairie voles.

Seasonal breeding of rodents is often associated with changes in adrenal function; altered adrenal function could account, in part, for seasonal changes in immune function and, ultimately, influence seasonal fluctuations in survival. Animals commonly monitor the annual change in photoperiod to ascertain the time of year and to make appropriate seasonal adjustments in physiology and behavior. Several extrinsic factors affect reproductive responsiveness to photoperiod. The interaction between population density and reproductive and adrenal responsiveness to photoperiod was assessed in the present experiment. Adult male prairie voles (Microtus ochrogaster) were maintained individually for 10 wk in long [light:dark (LD) 16:8] or short (LD 8:16) photoperiods in rooms with either high (10.96 animals/m3) or low (0.18 animals/m3) population densities. Regardless of population density, short-day voles regressed the size of their reproductive organs; reproductive organ masses were higher in long-day voles housed in high-density compared with low-density rooms. Paired adrenal masses were reduced in short-day voles, but were unaffected by population density; serum corticosterone concentrations were significantly elevated in short-day compared with long-day animals. In both photoperiods, basal blood corticosterone levels were higher in voles from low-density compared with high-density rooms. Splenic masses were unaffected by day length, but were elevated among high-density animals. Similarly, serum immunoglobulin (IgG) levels were elevated among high-density animals. These results suggest that population density per se, in the absence of behavioral interactions, can affect reproductive size, and possibly function, in long-day conditions, and that prairie voles, which are highly social, exhibit higher corticosterone and lower IgG levels in low compared with high densities. These results may be important in understanding arvicoline population fluctuations, as well as improving animal husbandry practices in the lab.

Animals↗
PubMed1996

Gonadal and photoperiodic influences on body mass regulation in adult male and female prairie voles.

Nontropical animals commonly use the annual change in photoperiod to phase seasonal adjustments that promote survival and reproduction. To cope with the energetic requirements of winter, many rodents alter body mass in anticipation of winter. Photoperiodic adjustments are often mediated by the pineal hormone melatonin; melatonin can exert a primary effect on body mass or secondarily affect body mass by changing blood gonadal steroid levels. The present study sought to determine if prairie voles (Microtus ochrogaster) alter body mass in response to short photoperiods. The role of the gonads in body mass regulation was also assessed. In experiment 1, males housed in short days increased body mass at a greater rate than long-day animals. Gonadectomy enhanced the body mass gain in short-day voles. These data suggest that the gonads contribute to short photoperiod-induced changes in body mass in male voles. In experiment 2, females housed in short days increased body mass at a greater rate than long-day animals, regardless of whether the animals were ovariectomized. Ovariectomy did not affect body mass in either long- or short-day animals, suggesting that the ovaries do not contribute to photoperiod-mediated changes in body mass in female prairie voles. Taken together, these studies suggest that male and female prairie voles use photoperiodic information to time seasonal changes in body mass.

Adipose Tissue↗
PubMed1996

Cellular immunity is not compromised by high serum corticosterone concentrations in prairie voles.

Glucocorticoids compromise immune function in glucocorticoid-sensitive species (e.g., mice), but these immunosuppressive effects may be reduced in glucocorticoid-resistant species. Prairie voles (microtus ochrogaster) have been characterized as glucocorticoid-resistant to their high circulating levels of corticosterone. Because glucocorticoid-sensitive species display suppressed lymphocyte proliferation in response to elevated blood glucocorticoid levels, proliferative values were hypothesized to be reduced in house mice (Mus musculus) compared with prairie voles. Prairie voles exhibited significantly higher splenocyte proliferative responses to the T cell mitogen, Concanavalin A, despite having higher basal total and free serum corticosterone levels than mice. Neither total nor free serum corticosterone correlated with proliferative responses from either species. These data provide further evidence for glucocorticoid resistance in prairie voles and suggest that the interactions between the hypothalamic-pituitary-adrenal axis and the immune system in prairie voles may differ from those in mice or other glucocorticoid-sensitive species. Therefore, prairie voles may serve as a valuable animal model for the syndrome of glucocorticoid resistance in humans and the role of glucocorticoids in conditions characterized by a hyperactive immune system.

Animals↗
PubMed1996

Photoperiod and temperature interact to affect immune parameters in adult male deer mice (Peromyscus maniculatus).

Nontropical rodents often experience large seasonal fluctuations in both food availability and energy demands. The energy required for thermoregulation is highest during the winter when food availability may be at an annual minimum. Failure to cope with winter probably accounts, in part, for the increased prevalence of disease and death relative to that in summer. Winter conditions may elevate circulating glucocorticosteroid levels, which can compromise immune function. To increase the odds of surviving the energetic demands of winter, individuals of some rodent species appear to enhance immune function before conditions deteriorate. Previous laboratory studies suggest that immune enhancement can be induced by short days. These findings contrast with the results of several field studies reporting suppressed immune function during the winter. To resolve this conflict, the authors hypothesized that winter stressors present in field studies counteracted the short-day enhancement of immune function reported in laboratory studies. If true, then immune function of captive mice in short days should be compromised by low temperature or reduced food availability. Both ambient temperature and photoperiod were manipulated in the present study to assess their effects on immune parameters in male deer mice (Peromyscus maniculatus). Animals in short days regressed their reproductive systems and also displayed significantly higher immunoglobulin G (IgG) levels than did those in long days. Deer mice maintained in low temperatures had significantly reduced splenic masses and basal IgG levels independent of day length. Animals maintained in both short days and low temperatures displayed IgG levels comparable to those of mice in long-day/mild-temperature conditions. Animals maintained in long days and low temperatures had significantly higher serum corticosterone levels than did animals maintained in long days at mild temperatures. These data are consistent with the hypothesis that immune parameters are enhanced in short days to counteract stress-mediated immune suppression occurring during the winter.

Adipose Tissue↗
PubMed1996

Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase.

BACKGROUND: Nitric oxide (NO) has been implicated as a mediator of penile erection, because the neuronal isoform of NO synthase (NOS) is localized to the penile innervation and NOS inhibitors selectively block erections. NO can also be formed by two other NOS isoforms derived from distinct genes, inducible NOS (iNOS) and endothelial NOS (eNOS). To clarify the source of NO in penile function, we have examined mice with targeted deletion of the nNOS gene (nNOS- mice). MATERIALS AND METHODS: Mating behavior, electrophysiologically induced penile erection, isolated erectile tissue isometric tension, and eNOS localization by immunohistochemistry and Western blot were performed on nNOS- mice and wild-type controls. RESULTS: Both intact animal penile erections and isolated erectile tissue function are maintained in nNOS mice, in agreement with demonstrated normal sexual behaviors, but is stereospecifically blocked by the NOS inhibitor, L-nitroarginine methyl ester (L-NAME). eNOS is abundantly present in endothelium of penile vasculature and sinusoidal endothelium within the corpora cavemosa, with levels that are significantly higher in nNOS- mice than in wild-type controls. CONCLUSIONS: eNOS mediates NO-dependent penile erection in nNOS- animals and normal penile erection. These data clarify the role of nitric oxide in penile erection and may have implications for therapeutic agents with selective effects on NOS isoforms.

Animals↗
PubMed1996

Tricuspid valve surgery: 15-year experience.

Tricuspid valve surgery has been associated with a high operative mortality. This study reviewed 51 patients who underwent 53 tricuspid valve procedures between 1975 and 1989. Most patients (82%) had evidence of rheumatic heart disease. Twenty-six patients (51%) had 42 previous cardiac operations, most involving the mitral valve. Eighty-two percent of patients were New York Heart Association (NYHA) class III or IV preoperatively, and almost all patients had associated disease of other valves. The indication for operation was tricuspid regurgitation in 45 patients, infectious endocarditis in 4, and tricuspid stenosis in 2. The tricuspid abnormality was functional in 67% and organic in 33%. There were 32 tricuspid valve replacements, 20 annuloplasties, and 1 tricuspid valve excision. The hospital mortality rate was 11.8% (six patients). On statistical analysis, none of the perioperative variables were a significant risk factor for hospital mortality. Twenty-nine patients (51%) had postoperative complications. Postoperative functional status improved markedly with 80% in NYHA class I and 13% in class II. Long-term follow-up was attempted but was unsatisfactory in this transient, indigent population.

Adolescent↗
PubMed1995

Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase.

In addition to its role in blood vessel and macrophage function, nitric oxide (NO) is a neurotransmitter found in high densities in emotion-regulating brain regions. Mice with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding, long-term potentiation and long-term depression. The nNOS- mice are resistant to neural stroke damage following middle cerebral artery ligation. Although CO2-induced cerebral vasodilatation in wild-type mice is NO-dependent, in nNOS- mice this vasodilation is unaffected by NOS inhibitors. Establishing a behavioural role for NO has, until now, not been feasible, as NOS inhibitor drugs can only be administered acutely and because their pronounced effects on blood pressure and other body functions obfuscate behavioural interpretations. We now report a large increase in aggressive behaviour and excess, inappropriate sexual behaviour in nNOS- mice.

Aggression↗
PubMed1995

The effects of photoperiod on olfactory c-fos expression in prairie voles, Microtus ochrogaster.

Reproduction stops among the majority of prairie voles (Microtus ochrogaster) during the winter. Short day lengths suppress male reproductive function dramatically in the laboratory, but photoperiod exerts only subtle effects on female reproductive function. Thus, the regulation of seasonal breeding in this species remains partially unspecified. In contrast to commonly studied rodents, female prairie voles do not undergo spontaneous estrous cycles; rather, they are induced into estrus by exposure to chemosignals expressed in conspecific male urine. In the present study, the hypothesis was tested that seasonal breeding among female prairie voles in the field reflects photoperiod-mediated changes in the responsiveness of the chemosensory system to male urine. Responsiveness was assessed by localizing the product of the c-fos immediate early gene with an immunocytochemical procedure. Female prairie voles were maintained in either long (LD 16:8) or short (LD 8:16) photoperiods from birth until adulthood, and exposed to either male urine or skim milk. Immunocytochemistry for fos protein revealed an increased number of immunoreactive cells within the accessory olfactory system of female prairie voles, including the accessory olfactory bulbs, granule cell layer, as well as the medial and cortical divisions of the amygdala 1 h after exposure to a single drop of urine as compared to individuals exposed to skim milk. The number of immunoreactive fos cells induced in females by conspecific male urine was also affected by photoperiod; short day females displayed fewer immunoreactive fos neurons in the accessory olfactory system as compared to long-day animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1995

Photoperiodic effects on steroid negative feedback in female prairie voles (Microtus ochrogaster).

Breeding in prairie voles is mainly restricted to the autumn and winter of most years. The organization of estrus in female prairie voles is unusual because behavioral estrus is induced by chemosensory stimuli from the urine of adult conspecific males. Isolated females exhibit undetectable levels of estradiol and never display estrous behavior, yet exposure to male urine causes a cascade of endocrine changes that evoke estrogen secretion from the ovaries and estrous behavior within 24 hr. In the prairie vole, the extreme dependence of estrus on chemosensory stimuli raises the possibility that their ovaries may be less prominent in the regulation of gonadotropin secretion than in species with more endogenously organized estrous cycles. The present study examined the contribution of the ovaries in luteinizing hormone (LH) regulation in prairie voles. Females were maintained for 9 weeks in either long (LD 16:8) or short (LD 8:16) photoperiodic conditions, a blood sample was obtained, and then animals were either ovariectomized or received a sham procedure. Another blood sample was obtained a week later and assayed for serum LH. Blood serum LH levels were significantly reduced in short-day voles, compared to long-day animals. After ovariectomy both long-day and short-day voles exhibited equivalent elevations in LH levels. This study provides evidence that photoperiod is measured in female voles and the ovaries appear to produce sufficient steroids to suppress LH release.

Animals↗
PubMed1995

Rhythmically firing (20-50 Hz) neurons in monkey primary somatosensory cortex: activity patterns during initiation of vibratory-cued hand movements.

The activity patterns of rhythmically firing neurons in monkey primary somatosensory cortex (SI) were studied during trained wrist movements that were performed in response to palmar vibration. Of 1,222 neurons extracellularly recorded in SI, 129 cells (approximately 11%) discharged rhythmically (at approximately 30 Hz) during maintained wrist position. During the initiation of vibratory-cued movements, neuronal activity usually decreased at approximately 25 ms after vibration onset followed by an additional decrease in activity at approximately 60 ms prior to movement onset. Rhythmically firing neurons are not likely to be integrate-and-fire neurons because, during activity changes, their rhythmic firing pattern was disrupted rather than modulated. The activity pattern of rhythmically firing neurons was complimentary to that of quickly adapting SI neurons recorded during the performance of this task (Nelson et al., 1991). Moreover, disruptions of rhythmic activity of individual SI neurons were similar to those reported previously for local field potential (LFP) oscillations in sensorimotor cortex during trained movements (Sanes and Donoghue, 1993). However, rhythmic activity of SI neurons did not wax and wane like LFP oscillations (Murthy and Fetz, 1992; Sanes and Donoghue, 1993). It has been suggested that fast (20-50 Hz) cortical oscillations may be initiated by inhibitory interneurons (Cowan and Wilson, 1994; Llinas et al., 1991; Stern and Wilson, 1994). We suggest that rhythmically firing neurons may tonically inhibit quickly adapting neurons and release them from the inhibition at go-cue onsets and prior to voluntary movements. It is possible that rhythmically active neurons may evoke intermittent oscillations in other cortical neurons and thus regulate cortical population oscillations.

Acclimatization↗
PubMed1995

Influence of photoperiod, green food, and water availability on reproduction in male California mice (Peromyscus californicus).

California mice (Peromyscus californicus) breed primarily during the winter rainy season and generally terminate breeding during the dry summer months. This pattern of reproduction could be regulated by day length, availability of green vegetation, or water availability. The effects of photoperiod and green vegetation on reproduction were examined in Experiment 1 by housing adult male P. californicus either in long (LD 14:10) or short (LD 8:16) photoperiods for 10 weeks with ad lib food and water availability. A subset of animals in each photoperiod treatment group also received supplements of fresh spinach thrice weekly. The effects of water availability were examined in Experiment 2 by housing adult males in long day length conditions for 10 weeks with ad lib or restricted (50% of ad lib) water availability. Neither photoperiod nor availability of green plant food significantly affected reproductive function in male California mice, although animals in long days with green food supplements displayed elevation of some reproductive organ masses. Short days did not suppress plasma LH or prolactin levels. Male P. californicus provide extensive care of the young during the short days of winter. The absence of photoperiod-induced changes in prolactin levels is consistent with the observation that elevated plasma prolactin titers are associated with male parental care in this species. In contrast, water restriction (simulated summer drought) reduced reproductive organ masses, as well as plasma levels of prolactin, and may act as an environmental cue to terminate breeding. Thus, water availability may regulate breeding in this species independently of photoperiod and food availability.

Animal Feed↗