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Biomedical subjects

M E Stanton

Publications and source records attributed to M E Stanton.

At least 55 records · Page 3Linked to original sources
PubMed1984

Posterodorsal septal lesions impair performance on both shift and stay working memory tasks.

Two groups of rats were trained preoperatively on either a shift or a stay problem in a T-maze. Training trials consisted of two runs, an "information run" in which a subject was forced to go down one of the two arms of the T-maze, followed immediately by a "choice run" in which the subject could choose either arm. In the shift condition, rats were rewarded with wet mash only for choosing the arm opposite the one they entered on the information run. In the stay condition, rats were rewarded for entering the arm that was entered on the information run. In both conditions, rats ultimately learned to perform with median accuracy of 100%, but the shift group reached this level of performance after fewer trials than the stay group. In a subsequent phase, the delay between information runs and choice runs was increased from 0 to 30, 60, 90, 210 and then decreased back to 0 s. Choice accuracy in both groups declined as the delay increased and returned to 100% at the 0-s delay. Half of the subjects in each condition then received either lesions of the posterodorsal septum-aimed at disconnecting the septum and hippocampus-or control surgery. Postoperative retention deficits resulted from posterodorsal septal lesions in both shift and stay conditions. There was some recovery of performance but no indication of "savings" during postoperative training. These results indicate that deficits in maze performance by rats with septo-hippocampal damage are not restricted to tasks that require alternation of spatial locations. This finding falsifies the notion that maze deficits reflect a spontaneous alternation deficit or changed "spatial strategy," but it supports the hypothesis of a working memory deficit in these animals.

Animals↗
PubMed1983

Memory and the septo-hippocampal cholinergic system in the rat.

This study examined the effects of intrahippocampal injections of scopolamine (a muscarinic antagonist drug) on performance of a working-memory task (contingently reinforced T-maze alternation) and a reference-memory task (visual discrimination) by the same rats in the same maze. Rats in the first shipment were trained in delayed alternation, received bilateral implantation of cannulae aimed at the CA 3 field of the dorsal hippocampus, and were tested for retention with 1 microliter microinjections of scopolamine (35 micrograms) and saline on alternate days. These rats were then trained on visual discrimination and tested alternately under scopolamine or saline as described above. It was found that scopolamine impaired performance of delayed alternation to a greater extent than performance of visual discrimination. Data from rats in the second shipment replicated this finding, with the order of the tasks reversed, and, additionally, showed that delayed alternation, but not visual discrimination, was impaired at a dose of 12 micrograms/microliter. A dose of 4 micrograms/microliter had no effect on either task. It is concluded that performance of a working-memory task is significantly more sensitive to disruption of cholinergic mechanisms in the hippocampus than performance of a reference-memory task.

Animals↗
PubMed1983

Adrenal responses to reinforcement and extinction: role of expectancy versus instrumental responding.

Plasma corticosterone levels were evaluated during operant conditioning in order to determine the effect of reinforced and nonreinforced responding (extinction) on adrenal activation. The influence of instrumental responding was assessed by comparing trained rats with yoked subjects that received a matched reward schedule in the absence of an operant task. Reinforcement sessions resulted in a significant decrease in adrenal secretion at 20 min, but not at 5 min, whereas extinction caused a rapid increase in corticosterone levels at 5 min and an even greater elevation by 20 min. Comparison of the operant and yoked subjects showed that this effect of reinforcement and extinction was not dependent on instrumental responding, but rather on the receipt or withdrawal of the expected reward.

Animals↗
PubMed1983

A general equation describing frequency discrimination as a function of frequency and sensation level.

Frequency-discrimination thresholds, for a wide range of stimulus frequencies and stimulus levels, were obtained from three normal-hearing listeners. Linear regression analyses of the present data, and of data from two previous studies, indicate that an SL-1 transformation of stimulus level and a square root F transformation of stimulus frequency yield linear dimensions that allow accurate predictions of frequency-discrimination thresholds from normal-hearing listeners over a wide range of stimulus frequencies (125-8000 Hz) and stimulus levels (5-8 dB SL) with a single prediction equation.

Humans↗
PubMed1982

Frequency discrimination at 1200 Hz in the presence of high-frequency masking noise.

To evaluate the possible contribution of high-frequency hearing to frequency discrimination at lower frequencies, pure-tone frequency discrimination tasks at 1200 Hz, with and without high-frequency masking noise, were performed by two highly practiced normal-hearing listeners. Signal levels ranged from 10 to 80 dB SPL. Spectra of the three high-frequency masking noises ranged from 1.8 to 2.1 kHz, from 2.8 to 3.1 kHz, and from 4 to 8 kHz. The frequency difference limen (DLF) intensity functions, describing DLFs as a function of signal level which were obtained in the presence of high-frequency masking noise, were essentially the same as the DLF intensity functions obtained without masking noise. These results indicate that high-frequency hearing is not necessary for acute frequency discriminations at low and at middle frequencies.

Adult↗
PubMed1977

Harvey Cushing: "From tallow dip to television".

Harvey Cushing was not only a leading founder of neurosurgery, but his work in general surgery provoked research which advanced medical knowledge, and he made substantial contributions to medical education and general literature. He discovered (with L.E. Livinggood) that the stomach and small intestine could be rendered sterile by fasting before operations; he successfully sutured the cervical thoracic duct without subsequent leakage; he suggested, after attempted repair of chronic valvular lesions in the dog, the possibility of surgery on cardiac valves in man; he demonstrated the relation of intracranial pressure to blood pressure; he devised one of the first charts for recording pulse and respiration and introduced routine blood pressure determinations during operation; and he stimulated continuing research by internists and endocrinologists through his work on the pituitary body and its disorders-work which was crowned by his discovery of pituitary basophilism. His unique course in operative surgery for medical students at the Johns Hopkins was adopted by other medical schools and he advanced other provocative theories concerning the organization and content of the medical curriculum. He provided elective clinics at Harvard Medical School for students and established postgraduate fellowships at the Hopkins, Harvard, and Yale schools of medicine. Cushing brought distinction upon himself and the medical profession through his books and essays of high literary quality and originality, most notably his biography of Sir William Osler, which was awarded a Pulitzer Prize in 1926.

Education, Medical, Graduate↗
PubMedDate not supplied

Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging.

Neonatal Long-Evans rats dosed with TET (5 mg/kg; IP) or saline on postnatal day (PND) 10 were examined across the life span for neural damage and performance on spatial learning tasks. A subset of rats were sacrificed to assess early damage with Nissl-staining, Timm's histochemistry, and glial fibrillary acidic protein (GFAP) immunohistochemistry 2, 7, or 14 days after dosing. Littermates were tested behaviorally in a T-maze spatial delayed alternation task on PND 23 or PND 90, and in a Morris water maze place learning task at 3, 12, or 24 months postdosing and then sacrificed for histological analysis. In neonatal rats, histological analysis indicated gliosis in discrete cortical regions, loss of Nissl-stained neurons in the hippocampal formation, entorhinal cortex and piriform cortex, and loss of Timm's staining in the entorhinal cortex. The behavioral assessment at PND 23 indicated a significant impairment in the T-maze. However, no significant impairments were observed in the T-maze at 3 months or the water maze at 3 or 12 months postdosing. At 24 months, TET-treated rats showed significant deficits in acquisition and retention of the water maze task compared with age-matched controls. Both groups of 24 months old rats were significantly impaired compared with young controls. At 24 months, there was a general age-related decrease in the optical density of Timm's staining in cortical regions (9%), compounded by a further decrease in the entorhinal cortex and outer molecular layer of the dentate gyrus of the hippocampus in TET treated rats (30%). These data indicate that early developmental exposure to an organometal resulted in morphological damage that was apparent behaviorally only during early postnatal development and with advanced aging.

Aging↗
PubMedDate not supplied

Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group I report: comparability of measures of developmental neurotoxicity in humans and laboratory animals.

Assessment measures used in developmental neurotoxicology are reviewed for their comparability in humans and laboratory animals, and their ability to detect comparable adverse effects across species. Compounds used for these comparisons include: substances of abuse, anticonvulsant drugs, ethanol, methylmercury, lead, PCBs, and ionizing radiation. At the level of functional category (sensory, motivational, cognitive and motor function, and social behavior), close agreement was found across species for all neurotoxic agents reviewed, particularly at high exposure levels. This was true even though the specific end points used to assess these functions often varied substantially across species. In addition, it was found that: 1) the U.S. EPA Developmental Neurotoxicology Test Battery presented at the Workshop would have identified the hazard to humans of exposure to the above compounds, although it may have underestimated human risk in some cases; 2) assessment of developmental neurotoxicity should involve evaluation of all categories of function; 3) for most compounds reviewed, the neurotoxic effects of prenatal exposure cannot be attributed to maternal toxicity, and exposure at or just below the threshold for such toxicity is an appropriate upper level for developmental neurotoxicity testing; 4) maternal exposure during the postnatal period poses a number of serious methodological problems; and 5) animal studies would better parallel human studies if more emphasis was placed on evaluation during development.

Animals↗
PubMedDate not supplied

Neonatal exposure to triethyltin disrupts olfactory discrimination learning in preweanling rats.

Triethyltin is an organotin compound that is known to produce neurotoxicity in both adult and developing organisms. Although this neurotoxicity has been documented with a variety of behavioral and biological measures, the effects of this compound on learning during early development have been less extensively studied. The present study reports four experiments that examined this question with an odor aversion learning paradigm in which pups received presentations of one odor paired with footshock and an alternate odor without shock. In Experiment 1, Long-Evans rat pups were injected IP on postnatal day 5 (PND 5) with either 0, 3 or 5 mg/kg TET and then tested for olfactory discrimination learning on PND 18. Only the 5-mg/kg dose impaired discrimination learning. In Experiment 2, PND 5 exposure to TET (5 mg/kg) disrupted olfactory learning on PND 18 but not on PND 12, whereas exposure on PND 10 disrupted learning at both ages of testing. In Experiment 3, PND 16 exposure to TET (5 mg/kg) also disrupted acquisition of olfactory learning on PND 18 but had no effect on retention of an olfactory discrimination that was acquired prior to TET exposure (i.e., on PND 14 and PND 15). Unconditioned responses to footshock were also unaffected by TET (Experiment 4). These findings indicate that neonatal exposure to TET impairs associative learning in developing rats and are discussed in relation to other studies of the developmental neurotoxicity of this compound.

Aging↗
PubMedDate not supplied

Neonatal exposure to trimethyltin disrupts spatial delayed alternation learning in preweanling rats.

Trimethyltin is an organotin compound that produces marked neurotoxicity in both adult and developing animals. The limbic system is a primary CNS target site for this toxicity, and a prominent behavioral effect of TMT is disruption of learning and memory. Impairment of cognitive development has also been suggested by studies showing that rats neonatally exposed to TMT cannot perform spatial working memory tasks during adulthood. However, the question of how early in ontogeny such deficits can be detected has not been addressed. The present study examined this question with a T-maze delayed alternation learning paradigm. Long-Evans rat pups, injected IP on Postnatal Day 10 (PND 10) with 6 mg/kg TMT and tested on PND 18, were unable to learn delayed alternation in the manner shown by vehicle control pups. However, TMT- and vehicle-treated groups were both able to learn a simple position discrimination. These findings indicate a selective impairment of spatial working memory by neonatal TMT exposure and show that this impairment can be demonstrated during the preweanling period in the rat.

Aging↗
PubMedDate not supplied

Developmental neurotoxicity following neonatal exposure to 3,3'-iminodipropionitrile in the rat.

Adult exposure to the neurotoxicant 3,3'-iminodipropionitrile (IDPN), induces a hyperkinetic syndrome consisting of spontaneous head movements, abnormal circling, backward locomotion, and sensory disruption. We report here the behavioral effects of developmental exposure to IDPN in the rat. Animals were exposed (IP) to either saline, 75, 150, or 300 mg/kg/day on postnatal days (PND) 5-7. Animals were tested for: Figure-8 maze activity (PND 13-60); olfactory discrimination learning (PND 18 & 24); T-maze alternation and position discrimination learning (PND 25 & 26); acoustic startle response (PND 23, 61, & 62); passive avoidance (PND 70). To better define the dose response, a separate group of animals was exposed to either saline or 225 mg/kg/day (PND 5-7) and tested in the activity, T-maze, and startle paradigms. Animals exposed to 225 mg/kg/day and 300 mg/kg/day had decreased weight gain and lethality was 25% in the latter group. Signs of the IDPN syndrome, evident in the 225 and 300 mg/kg/day groups, persisted throughout the course of the study. IDPN exposed animals (300 mg/kg/day) were hyperactive on PND 17-60, failing to develop habituation in the Figure-eight maze until PND 60. The acoustic startle response was depressed for the 225 and 300 mg/kg/day groups on PND 23 only. Auditory thresholds were elevated for a high-frequency (40 kHz) but not a low-frequency tone (5 kHz) for the 225 and 300 mg/kg/day groups, indicating a hearing loss. IDPN treatment also disrupted performance of olfactory discrimination learning and produced cognitive deficits in T-maze learning in infants (300 mg/kg/day). That cognitive deficits also appeared in adulthood (PND 70) was demonstrated by learning deficits in a passive avoidance task at 150 and 300 mg/kg/day. IDPN (300 mg/kg/day) also caused a decrease in the wet weight of the whole brain (8%) and the cerebellum (12%) but not the hippocampus. These data demonstrate that short-term, neonatal exposure to IDPN in the rat produced persistent alterations in sensory, motor, and cognitive aspects of nervous system function.

Animals↗
PubMedDate not supplied

Ontogeny of the conditioned eyeblink response in rats: acquisition or expression?

Eyeblink conditioning depends critically on an identified brainstem-cerebellar circuit and is modulated under some circumstances by the hippocampus, amygdala, and other forebrain regions. Developmental studies of eyeblink conditioning could help elucidate questions concerning the behavioral expression of plasticity within these brain circuits and regions, and of their functional interactions, as they unfold during ontogeny. Recently, this laboratory has shown that conditioning of the eyeblink reflex develops dramatically between Postnatal Days (PND) 17 and PND 24 in the rat. The present study asked whether the developmental emergence of the eyeblink conditioned response (CR) occurs gradually or abruptly over this age range, and whether it reflects developmental changes in acquisition or expression of the learned eyeblink reflex. In Experiment 1, rat pups received two consecutive days of training beginning on PND 17, 20, or 24. Conditioned responses occurred at low levels on PND 17-18, intermediate levels on PND 20-21, and high levels on PND 24-25. In Experiment 2, 17-day-old rats received 2 days of training, 72 h apart, so that effects of training on PND 17 could be examined at an age, PND 20, when expression of the eyeblink CR was clearly possible. On PND 20, rat pups that had received paired training on PND 17 showed significantly faster conditioning than controls that had received unpaired training or no training on PND 17. These findings suggest that neural plasticity underlying associative learning developmentally precedes its overt expression in behavior. Hypotheses concerning the nature and locus of this learning are discussed.

Acoustic Stimulation↗
PubMedDate not supplied

Development of cholinergic neurons in rat brain regions: dose-dependent effects of propylthiouracil-induced hypothyroidism.

The effects of hypothyroidism on development of cholinergic system in brain regions (prefrontal cortex and hippocampus) were evaluated by measuring choline acetyltransferase (ChAT) activity and hemicholinium-3 binding to the high-affinity choline transporter. Various degrees of thyroid deficiency were produced by perinatal exposure to propylthiouracil (PTU) in drinking water ranging from 5 ppm (mg/l) to 25 ppm beginning at gestational day 18 until postnatal day 21. ChAT, a marker for cholinergic nerve terminals, was reduced by PTU in a dose-dependent manner. Concomitant with the enzyme deficits, hemicholinium-3 binding was elevated, suggesting an increase in neuronal impulse activity. Although similar changes were seen in both brain regions examined, the magnitude and duration of these changes were more definitive in the prefrontal cortex. Nonetheless, these neurochemical alterations appeared to be recoverable when the rats returned to a euthyroid state, and no further changes were observed as the animals reached adulthood. In comparison, data reported in a succeeding article indicate that deficits in cognitive function were first seen in weanling hypothyroid rats, but that the behavioral impairments lasted well into adulthood when thyroid status and cholinergic parameters in the brain appeared to have recovered to normal. These results suggest that alterations of cholinergic system caused by perinatal hypothyroidism are associated with neurobehavioral deficits at weaning, and these developmental deviations may cause permanent impairment of cognitive function despite recovery from the hormonal imbalance at adult ages.

Animals↗