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Biomedical subjects

M Leon

Publications and source records attributed to M Leon.

At least 127 records · Page 7Linked to original sources
PubMed1989

Induction of tyrosine hydroxylase expression in rat forebrain neurons.

Olfactory nerve input is required for the normal expression of tyrosine hydroxylase (TH) by dopaminergic neurons in the glomerular region of the rodent main olfactory bulb. To determine whether the olfactory nerve exerts a similar influence on neurons in other brain regions, we performed unilateral bulbectomies in rat pups on postnatal day 5-7 and examined the brains 2-6 months later, after the regenerated olfactory nerve had penetrated the forebrain. Tissue was stained for TH, dopamine beta-hydroxylase (DBH) and olfactory marker protein immunoreactivity. We observed novel TH-immunoreactivity in neurons located in those areas of the adult forebrain which received olfactory nerve fibers, particularly the rostral extension of the subependymal layer. Many of these neurons resembled the periglomerular cells of the olfactory bulb. No cell staining for DBH was observed in these areas, suggesting the possible dopaminergic phenotype of these neurons. Our data indicate that afferent regulation of neurotransmitter expression by the olfactory nerve is not limited to the cells of the olfactory bulb.

Animals↗
PubMed1989

NGF receptor increase in the olfactory bulb of the rat after early odor deprivation.

In the olfactory bulb of normal rats, nerve growth factor (NGF) receptor (NGFR) immunoreactivity was largely confined to the glomerular layer. Unilateral closure of the nostril at postnatal day 2 (P2) increased NGFR immunoreactivity in the sealed bulb at both 19 and 60 days after the operation. The increase in NGFR density, measured by autoradiographic immunohistochemistry, was most dramatic 60 days postocclusion. These findings suggest that a compensatory increase in NGFRs may play a role in the maintenance of bulbar function after the early loss of sensory stimulation.

Animals↗
PubMed1989

Study of bone loss in diabetes mellitus type 1.

While people with type 1 diabetes mellitus (DM) often have bone deficiency, the relation between this deficiency and the duration or control of diabetes remains controversial. To assess the possibility of such an interrelationship, we studied parameters relating to mineral metabolism (Ca, P, alkaline phosphatase, Mg, PTH, and hydroxyproline (OHP)); bone remodeling (osteocalcin); diabetic control (HbA1c); and radiological study of the second metacarpal of the left hand and of bone age in 87 children with type 1 DM. The mineral parameters were not abnormal among the diabetics. Diabetic children had similar levels of fasting osteocalcin as normals (10.05 +/- 4.9 vs. 9.79 +/- 3.34 ng/ml, mean +/- SD); this did not differ by sex. The bone age fell within two standard deviations of the mean, and 9.5% of the diabetics had a bone mass deficit (less than the mean cortical thickness) greater than 2 SD. There was no correlation between osteocalcin and Ca, P, glycemia, HbA1c, PTH, Mg, or OHP. Our results do not support any association between bone mass loss and the severity or duration of type 1 diabetes. Bone turnover, measured by serum osteocalcin, was normal. Therefore the pathogenesis of osteopenia in type 1 DM remains unclear, and requires further investigation.

Alkaline Phosphatase↗
PubMed1989

Norepinephrine and learning-induced plasticity in infant rat olfactory system.

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses.

Animals↗
PubMed1988

Noradrenergic modulation of olfactory bulb excitability in the postnatal rat.

Noradrenergic centrifugal inputs to the rat olfactory bulb mainly terminate on granule cells, which are inhibitory interneurons. In the mature bulb, norepinephrine suppresses granule cell activity, thus increasing the excitability of the primary output neurons of the bulb. However, since the majority of granule cells develop postnatally, the effectiveness of noradrenergic inputs to the bulb during development is unclear. The present report describes the postnatal development of noradrenergic modulation of olfactory bulb function by examining the effects of noradrenergic beta-receptor agonists and antagonists on paired-pulse inhibition at the granule cell/mitral cell reciprocal synapse. The results demonstrate that noradrenergic modulation of olfactory bulb excitability emerges during the first postnatal week in the rat. These results suggest that noradrenergic centrifugal control of olfactory bulb activity appears early during postnatal development, and thus is capable of playing an important role in pup responses to olfactory cues early in life.

Action Potentials↗
PubMed1988

NMDA receptor activation and early olfactory learning.

Norway rat pups have an enhanced olfactory bulb response to odors which they have learned to prefer early in life. When N-methyl-D-aspartate receptors are blocked pharmacologically before olfactory preference training, both the behavioral preference and the enhanced olfactory bulb response to the learned odor are suppressed. These results implicate the activation of these receptors in the kind of neural and behavioral plasticity that normally occurs during development.

2-Amino-5-phosphonovalerate↗
PubMed1988

Physical stimulation reduces the body temperature of infant rats.

Physical stimulation of rat pups, of the type normally received from the mother, has been shown to regulate several behavioral and physiological systems in the young. The present paper describes a possible role of physical stimulation in an additional physiological system; the thermoregulatory system. Within a thermoneutral environment, physical stimulation produces a decrease in rectal temperature (Expt. 1). Even in an environment of increasing temperature, similar to that pups experience when in contact with the dam, physical stimulation attenuates an increase in rectal temperature (Expt. 2). The physiological mechanism of heat loss appears to involve ventilatory heat exchange resulting in convective and evaporative heat loss (Expts. 3, 4). Furthermore, physical stimulation continues to produce a decrease in rectal temperature throughout the preweanling period (Expt. 5). These results suggest that pups may not always have to resort to behavioral thermoregulatory mechanisms which require them to separate themselves from their mother. Rather, pups may be cooled, or at least a heat gain attenuated, by physical stimulation from the dam while maintaining contact with her.

Animals↗
PubMed1988

Physical stimulation reduces the brain temperature of infant rats.

Previous work indicated that physical stimulation, such as that which mimics the stimulation pups receive from the dam, reduces pup body temperature. The present paper reports that the body and brain temperature of 5-day-old pups covaried under steady-state thermal conditions, cold exposure, and warmth exposure (Expt. 1) suggesting that body thermoregulatory mechanisms may also regulate brain temperature. Indeed, physically stimulating pups decreased brain temperature in the neocortex (Expt. 2) and the olfactory bulb (Expt. 3). The mechanism for this brain temperature decrease appears to be an increase in ventilatory heat exchange, the same mechanism responsible for the decrease in body temperature. Pups increased respiration during stimulation, thereby increasing air flow to the lungs where convective and evaporative heat exchange occurred. Indeed, stimulating pups in a high-humidity environment blocked the decrease in brain temperature (Expt. 4). The ability of physical stimulation to decrease brain temperature appears to be limited to neonatal pups, as 10-, 15-, and 20-day-old pups did not exhibit a brain temperature decrease in response to stimulation (Expt. 5).

Animals↗
PubMed1988

Behavioral and neural correlates of postnatal olfactory conditioning: I. Effect of respiration on conditioned neural responses.

Following olfactory classical conditioning, infant rats exhibit a preference for the conditioned odor and exhibit enhanced uptake of focal 14C 2-deoxyglucose (2-DG) within the olfactory bulb. The present experiments assessed the role of respiration on the expression of the enhanced 2-DG uptake response. Pups were conditioned from postnatal day (PN) 1-18 with an olfactory stimulus paired with a reinforcing tactile stimulus which mimics maternal contact (Odor-Stroke). Control pups received odor only or tactile stimulation only. On PN 19, pups received 1 of 3 tests: 1) a two-odor choice test, 2) an odor/2-DG test with normal respiration allowed, or 3) an odor/2-DG test with respiration experimentally controlled. The results indicated that: 1) Odor-Stroke pups learned the conditioned odor preference, 2) Odor-Stroke, normally respiring pups exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups. No difference in respiration rate was detected between groups in normally respiring pups. 3) Odor Stroke pups whose breathing was experimentally controlled exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups with an identical number of respirations. Together, these results demonstrate that modified respiration during testing is not required for the expression of a modified olfactory bulb response to learned attractive odors. Therefore, the data suggest that the olfactory system itself is modified by early learning.

Animals↗
PubMed1988

Spatial patterns of olfactory bulb single-unit responses to learned olfactory cues in young rats.

1. Neonatal rat pups were classically conditioned to an odor stimulus from postnatal day 1 (PN1) to PN18. Tactile stimulation (stroking) was used as the unconditioned stimulus. On PN19, mitral/tufted cell single-unit responses to the conditioned odor were examined in both conditioned and control pups. Recordings were made from mitral/tufted cells in two regions of the olfactory bulb: 1) an area typically associated with focal [14C]2-deoxyglucose (2-DG) uptake in response to the conditioned odor and 2) an area distant from focal 2-DG uptake to the conditioned odor. Animals were anesthetized with urethane and were naturally respiring during the single-unit recording procedure. 2. Changes in mitral/tufted cell firing rate in response to odors in both bulbar regions and all training groups were classified as either excitatory, suppressive, or no response. This response classification was used to compare response patterns to the conditioned odor between bulbar regions and training groups. 3. Classical conditioning selectively modified the response patterns of mitral/tufted cells to the conditioned odor when those cells were associated with regions of focal 2-DG uptake for that odor. Mitral/tufted cells demonstrated significantly more suppressive and fewer excitatory responses to the conditioned odor than cells in control pups. Response patterns to a novel odor were not similarly modified. 4. Response patterns of mitral/tufted cells distant from the focal region of 2-DG uptake to the conditioned odor were not modified by conditioning compared with control pups. 5. The difference in response pattern between cells in the 2-DG focus and cells distant to the 2-DG focus was apparent within 500 ms of the stimulus onset. Given the respiratory rate of these pups (2 Hz), these data suggest that the modified response pattern occurred on the first inhalation of the learned odor. 6. These data demonstrate that both spatial and temporal patterns of olfactory bulb output neuron activity are used in the coding of olfactory information in the bulb. Furthermore, these spatial/temporal response patterns can be modified by early learning.

Animals↗
PubMed1987

Sensitive period for neural and behavioral response development to learned odors.

Olfactory preference training early in life produces both a behavioral preference and an enhanced uptake of 2-deoxy-[14C]glucose (2-DG) in specific areas of the olfactory bulb glomerular layer. We now describe a sensitive period during the first week after birth for the development both of the enhanced neural response and the behavioral preference.

Aging↗
PubMed1987

Localized changes in olfactory bulb morphology associated with early olfactory learning.

Young rats exposed to an odor while receiving reinforcing stimulation come to approach that odor upon subsequent presentation. In addition, such pups have increased 14C-2-deoxyglucose (2DG) uptake within focal areas of the glomerular layer in response to that odor, compared to control animals experiencing the odor for the first time. In this study, the morphology of the glomerular areas underlying these 2DG foci was examined to determine whether early olfactory learning imposed local structural changes that could produce the enhanced 2DG uptake. Alternate sections either were processed with a silver and a Nissl stain to label both cell bodies and their processes or were histochemically treated for the mitochondrial enzymes cytochrome oxidase (CO) or succinic dehydrogenase (SDH) to define the glomerular core of the bulb; 2DG autoradiographs were aligned with adjacent stained sections, and regions underlying the high 2DG uptake foci were examined. In odor-familiar animals, large glomerular clusters that protruded into the external plexiform layer or the olfactory nerve layer were associated with the focal areas of increased 2DG uptake. Morphometric analysis of these regions revealed that the glomerular layer underlying the foci of high 2DG uptake was 30% wider in odor-familiar animals than comparable areas in odor-unfamiliar animals; the cross-sectional areas of individual glomeruli were 21% larger in odor-familiar animals. The foci of enhanced 2DG uptake therefore appear to be associated with groups of enlarged glomeruli. These data demonstrate that early olfactory learning influences the morphology of the olfactory bulb.

Animals↗