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T C Foster

Publications and source records attributed to T C Foster.

At least 37 records · Page 2Linked to original sources

Age-associated changes in Ca(2+)-dependent processes: relation to hippocampal synaptic plasticity.

Altered calcium (Ca2+) homeostasis is thought to play a key role in aging and neuropathology resulting in memory deficits. Several forms of hippocampal synaptic plasticity are dependent on Ca2+, providing a potential link between altered Ca2+ homeostasis and memory deficits associated with aging. The current study reviews evidence for Ca2+ dysregulation during aging which could interact with Ca(2+)-dependent synaptic plasticity. The authors suggest that changes in Ca2+ regulation could adjust the thresholds for synaptic modification, favoring processes for depression of synaptic strength during aging.

Aging↗

Mechanism of altered synaptic strength due to experience: relation to long-term potentiation.

An increase in medial perforant synaptic strength can be observed for hippocampal slices from rats exposed to environmental enrichment. The expression of enhanced synaptic strength exhibits properties similar to long-term potentiation (LTP), a physiological model of memory storage. Similarities include an increase in strength of the synaptic response in the absence of an altered paired-pulse ratio and an increase in the binding of the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. Furthermore, environmental enrichment interacts with the mechanisms responsible for the induction of LTP by inhibiting further increases in synaptic strength following LTP-inducing stimulation. The results provide evidence for experience-mediated influences on postsynaptic mechanisms regulating medial perforant path synaptic strength.

Analysis of Variance↗

Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging.

Homosynaptic long-term depression (LTD) and reversal of long-term potentiation (LTP) were examined extracellularly at CA3-CA1 synapses in stratum radiatum of slices from adult (6-9 months) and aged (20-24 months) Fischer 344 rats. Prolonged low-frequency stimulation (LFS) (900 pulses/1 Hz) of the Schaffer collaterals depressed the initial slope of the excitatory postsynaptic potential (EPSP) in aged but not adult rats. LTD at aged synapses was pathway-specific, persistent, and sensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Adult slices exhibited AP5-sensitive LTD in high [Ca2+] medium, whereas LTD in aged slices was blocked by high [Mg2+], suggesting that differences in Ca2+ regulation may underlie susceptibility to LTD. Despite age-related differences in LTD induction, no age difference in LTP magnitude was revealed. Additionally, LFS delivered 60 min after LTP induction resulted in similar LTP reversal for both age groups. Susceptibility differences to LTP reversal were indicated after multiple short-duration LFS bursts (30 pulses/1 Hz), with each burst separated by 10 min. Aged synapses exhibited significant reversal after a single burst and complete reversal after three LFS episodes. In adult slices, LTP reversal appeared after the fourth burst, and at no time was LTP depressed to initial baseline levels. This study provides the first characterization of homosynaptic LTD/LTP reversal in the aged animal and demonstrates that one form of plasticity, depression attributable to LFS, is increased during aging.

2-Amino-5-phosphonovalerate↗

Age and stress history effects on spatial performance in a swim task in Fischer-344 rats.

This study determined whether prior habituation to water immersion would ameliorate age-related deficits in learning and memory in a swim task. Aged (22 months) and young adult (3 months) rats were immersed in water (30 degrees C) for 15 min on each of 28 consecutive days before training in the swim task. Additional groups of age-matched animals served as handled controls. Training on a spatial discrimination version of the water task was conducted over 5 days with two trials per day (1-h intertrial interval). A probe trial was substituted for the last trial on the fifth day to assess the rats' use of spatial information. Three days later, rats received cue discrimination training to find a visible platform. In the spatial task, prior habituation to water immersion ameliorated deficits in acquisition within each day (i.e., at a 1-h intertrial interval) but not across days (at 24 h). The results obtained with the 24-h interval confirm the rapid forgetting characteristic of aged rats in many tasks. The stress-habituation procedures reduced age-related deficits seen on the probe trial and on cue discrimination training. These findings indicate that several aspects of age-related impairments in the swim task, often attributed to primary age-related deficits in learning and memory processes per se, may instead be secondary to age-related differences in stress responses to water immersion.

Aging↗

Developmental increase in CA3-CA1 presynaptic function in the hippocampal slice.

1. We recorded extracellular and intracellular CA3-CA1 synaptic responses in hippocampal slices from neonatal rats [postnatal day (P) 15-21 and P29-35]. Presynaptic function was examined by measuring input-output relationships and paired-pulse facilitation and by quantal analysis of minimally evoked responses. 2. Extracellular recording revealed no difference in excitatory postsynaptic potential (EPSP) threshold or the fiber potential response for a given stimulus intensity between the two age groups. However, the slope of the field EPSP was consistently larger in older animals. The increase in EPSP slope was associated with a decrease in paired-pulse facilitation, suggesting an increase in presynaptic function with postnatal development. 3. Extracellular results were confirmed by intracellular recordings that revealed no difference in the minimal stimulation intensity needed to evoke a response, an increase in mean EPSP amplitude with development, and a decrease in paired-pulse facilitation. Quantal parameters were extracted by three separate methods including method of failures, coefficient of variance, and parameter optimization through noise deconvolution. All methods supported presynaptic mediation of facilitation. Comparison of quantal parameters during development indicated an increase in mean quantal content. 4. The results demonstrate that synaptic strength is altered over the course of development because of, at least in part, changes in presynaptic release mechanisms. Developmental differences in presynaptic function provide an explanation of differences in mechanisms for expression of long-term potentiation. The lower initial probability of transmitter release in neonates may permit increased presynaptic change.

Animals↗

Persistent increase of hippocampal presynaptic axon excitability after repetitive electrical stimulation: dependence on N-methyl-D-aspartate receptor activity, nitric-oxide synthase, and temperature.

The electrical excitability of Schaffer collateral axons and/or terminals was studied in hippocampal slices by monitoring single, CA3 pyramidal neurons activated antidromically from CA1 stratum radiatum. At 22 degrees C, weak, repetitive stimulation with as few as 10 impulses at 2 Hz led to a robust lowering of the antidromic activation threshold that lasted > 30 min. The effect was completely absent at 32 degrees C and was blocked by both the N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovalerate and the inhibitor of nitric-oxide synthase, L-nitro-arginine methyl ester. Such threshold lowering would alter the variance of synaptic responses from axons stimulated in the variable excitation region of their input-output functions. These results thus raise important doubts about the interpretation of experiments in which the so-called minimal-stimulation method has been used at reduced temperature to infer changes in quantal transmission during hippocampal long-term potentiation. In the present experiments, no changes were observed in the estimate of excitatory postsynaptic potential quantal content in long-term potentiation experiments at either temperature, which could not be accounted for by an artificial, temperature-dependent change in the responsiveness of presynaptic axons.

Amino Acid Oxidoreductases↗

Physiology of uterine activity in pregnancy.

During the past few years enormous progress has been made in the understanding of the molecular mechanisms involved in parturition; however, the answer to the fundamental question of how labor is initiated remains elusive. This is a very important question because alterations in the timing of birth (preterm and post-term deliveries) are associated with much of perinatal morbidity and mortality. Currently available treatments for preterm labor are not clearly effective. Prevention of preterm delivery by home uterine monitoring has been proposed; however, the value of this technique has not been conclusively shown. A variety of substances have been implicated in the genesis of labor, including oxytocin, prostaglandins, cytokines, and endothelin. The role of infection in preterm labor has also been extensively studied, but it seems clear that a relatively small percentage of preterm labor is caused by infection. Attention has also focused on the role of estrogen and progesterone, and the possible uses of progesterone antagonists in the induction of labor. A better understanding of the relationship of intrauterine hypoxia and preterm delivery may also help us in establishing treatment and prevention strategies.

Cardiotocography↗

Acetylcholine modulates averaged sensory evoked responses and perforant path evoked field potentials in the rat dentate gyrus.

The effect of localized application of acetylcholine (ACh) on well characterized components of sensory evoked and electrically induced potentials in the dentate gyrus was investigated in rats while performing a tone discrimination task. Local pressure application of ACh to the granule cell layer of the dentate gyrus through the recording pipette increased the amplitude of perforant path evoked population spikes without changing the amplitude of the field EPSP. When the pipette was relocated to the outer molecular layer of the dentate gyrus (OM), ACh application decreased the amplitude of the perforant path field EPSP. Two major components of the averaged auditory evoked potential (AEP) recorded during criterion performance of the discrimination task were significantly changed by dendritic application of ACh. The N1 component of the OM AEP which has been shown to reflect perforant path synaptic activity decreased in amplitude while the N2 component which represents activity from septal connections, was significantly increased. These effects were not due to the pressure ejection procedure nor drug related changes in behavioral performance of the task. The results suggest that ACh may act to differentially modulate the synaptic excitability of dentate granule cells, allowing them to acquire responses to sensory stimulation during the establishment and maintenance of discrimination learning.

Acetylcholine↗

Region-specific age effects on AMPA sensitivity: electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1.

The effects of aging on the responsiveness of hippocampal neurons to iontophoretic application of L-glutamate and AMPA were studied in vitro. There were no effects of age on neuronal responses to L-glutamate; however, CA1 pyramidal cells of old rats, but not granule cells in the fascia dentata, showed both a smaller reduction in extracellularly-recorded synaptic responses following application of AMPA (presumably mediated by depolarization), and smaller extracellular "DC" fields (measured by subtracting the DC potentials at the dendrite and soma following AMPA application in the dendrites). To examine the cellular bases of this age-related alteration in AMPA sensitivity, two additional electrophysiological approaches were used: (1) measurement of the amplitude ratios of extracellular EPSP and fiber potential components of the Schaffer collateral-CA1 response; (2) measurement of intracellularly recorded unitary EPSPs and quantal analysis of their fluctuations. The interpretations that would be placed on four hypothetical possible outcomes of such experiments are outlined and assessed in relation to the experimental data. The pattern of results obtained in the present experiments supports the following conclusions: In old rats, individual Schaffer collateral synapses do not appear to have altered AMPA receptor properties, as neither the mean size of the unitary synaptic response nor the apparent quantal size differs between age groups; however, the data do support the conclusion that there are fewer synapses per Schaffer collateral branch in old versus young CA1 pyramidal cells.

Aging↗

Long-term enhancement of CA1 synaptic transmission is due to increased quantal size, not quantal content.

Quantal components of Schaffer collateral synaptic transmission recorded intracellularly from CA1 pyramidal cells were examined using 2 methods: simultaneous recordings of CA3-CA1 cell-pairs, and minimal electrical stimulation in stratum radiatum. Quantal parameters estimated by the method of failures and by a computer algorithm that optimized parameter estimates using deconvolution of background noise were highly correlated. EPSP-amplitude histograms of CA3-CA1 cell pairs (N = 10) and minimal electrical stimulation (N = 33) could be adequately described either by Poisson or binomial statistics, or by both, and exhibited similar estimates of unit quantal size (q) and mean quantal content (m). Paired-pulse stimulation with 50 msec between stimuli resulted in an expected facilitation in the EPSP amplitude and increase in m during the second response, as estimated by noise deconvolution, by the decrease in apparent failures, and by a decrease in the coefficient of variation of the EPSP. Tetanization of the Schaffer collaterals that induced long-term enhancement (LTE/LTP) of the population response was associated with an average increase in q for minimal-stimulation responses, with no significant change in any estimate of m. Taken together, these data indicate that, under the present experimental conditions, LTE is expressed as an increase in quantal size, rather than an increase in the number of quanta released per presynaptic impulse. Although this is not definitive evidence for a postsynaptic mechanism, these findings do further restrict the classes of possible presynaptic mechanisms that may be proposed to account for LTE expression.

Action Potentials↗

Specificity of functional changes during normal brain aging.

Although there is no question that age-related alterations in neural function occur in the central nervous system (CNS) of mammals, these changes tend to be somewhat circumscribed rather than completely global, even in pathological conditions. Examples of this kind of specificity of functional neural change are drawn from experiments on the electrophysiology of the senescent rat hippocampus.

Aging↗

The cellular basis of memory.

In the Perspective "Too many rodent carcinogens: Mitogenesis increases mutagenesis" by Bruce N. Ames and Lois Swirsky Gold (31 Aug., p. 970), the last paragraph on page 970 (continuing on page 971) was incorrectly printed. It should have read, "One major group of natural chemicals in the human diet are the chemicals that plants produce to defend themselves, the natural pesticides (4). We calculate that 99.9% (by weight) of the pesticides in our diet are natural. Few natural pesticides have been tested in at least one rodent species, and again about half (27/52) are rodent carcinogens. These 27 occur commonly in plant foods (10). The human diet contains thousands of natural pesticides, and we estimate that the average intake is about 1500 mg per person per day (4). This compares to a total of 0.09 mg per person per day of residues of about 100 synthetic pesticides (4). In addition, of the mold toxins tested at the MTD (induding aflatoxin), 11 out of 16 are rodent carcinogens." Also, in paragraph 3 on page 970, "47,000 8-hydroxydeoxyguanosines per cell" should have been "90,000" per cell.

Animals↗

Use of magnesium sulfate to treat hyperstimulation in term labor.

Magnesium sulfate has been shown in vivo and in vitro to decrease the frequency of uterine contractions while maintaining the amplitude; we therefore decided to assess the use of magnesium sulfate infusion in cases of uterine hyperstimulation. The medical records were reviewed retrospectively for 37 term pregnant patients diagnosed as having uterine hyperstimulation during labor. None of them had medical or obstetric complications. Twenty-two of them received oxytocin augmentation for abnormal labor. Although the vast majority of these patients had a decrease of the hyperstimulation while being given the magnesium, 31.8% in the group receiving oxytocin alone (P less than .05). Fifteen additional patients received magnesium sulfate for uterine hyperstimulation although they were not receiving oxytocin; of these, 16.7% required cesarean delivery. This rate was no different from that of the patients who required labor augmentation, but was double the overall primary cesarean rate at our hospital. There appears to be a group of patients with abnormal uterine activity (either spontaneous or associated with oxytocin augmentation) that responds to treatment with magnesium sulfate.

Female↗

Spatial selectivity of rat hippocampal neurons: dependence on preparedness for movement.

The mammalian hippocampal formation appears to play a major role in the generation of internal representations of spatial relationships. In rats, this role is reflected in the spatially selective discharge of hippocampal pyramidal cells. The principal metric for coding spatial relationships might be the organism's own movements in space, that is, the spatial relationship between two locations is coded in terms of the movements executed in getting from one to the other. Thus, information from the motor programming systems (or "motor set") may contribute to coding of spatial location by hippocampal neurons. Spatially selective discharge of hippocampal neurons was abolished under conditions of restraint in which the animal had learned that locomotion was impossible. Therefore, hippocampal neuronal activity may reflect the association of movements with their spatial consequences.

Animals↗

Effects of delta-9-tetrahydrocannabinol on sensory evoked hippocampal activity in the rat: principal components analysis and sequential dependency.

The effects of delta-9-tetrahydrocannabinol (delta-9-THC) were assessed on identified hippocampal sensory evoked potentials obtained from rats during performance of a two-tone discrimination task. Techniques which analyzed the trial-to-trial sequential and serial dependence underlying the variance in evoked potential amplitude were utilized. Waveforms of averaged tone-evoked potentials (AEPs) recorded from the outer molecular layer of the dentate gyrus (OM) were subjected to principal components analysis which revealed eight principal components accounting for 90.3% of the total variance in the set of OM AEP waveforms. Five of the eight components were altered significantly in comparison to vehicle injection sessions after administration of either a 1.0- or 2.0-mg/kg dose of delta-9-THC. These alterations accounted for the amplitude and latency changes in the OM AEP described in a previous report. In addition, delta-9-THC also disrupted the trial-to-trial sequential dependency of the OM AEPs. An important result showed that delta-9-THC selectively influenced the serial dependence of the OM AEP. These results implicate delta-9-THC as a potent disruptor of temporally specific information as it is processed by the hippocampus and suggest that such disruption may be the basis of delta-9-THC effects on memory processes in humans.

Animals↗

Clinical management of patients with cystic fibrosis and pulmonary insufficiency.

Management of a patient with cystic fibrosis who started her pregnancy in a state of pulmonary insufficiency, as defined by arterial blood gas values and a chest x-ray film, is described. A systematic approach to evaluation of patients with cystic fibrosis, including serial assessments of pulmonary functions, screening for diabetes, maintenance of adequate nutrition (including hyperalimentation), and cardiac function evaluation is described.

Adult↗

Control of sensory activation of granule cells in the fascia dentata by extrinsic afferents: septal and entorhinal inputs.

Three groups of rats were trained to perform a differential discrimination task in a 2-tone operant conditioning paradigm. One group received electrolytic lesions of the medial septal nuclei, another received electrolytic or knife cut lesions of the entorhinal cortex. These groups were compared with a normal control group. Recordings of granule cells in the fascia dentata were obtained in all animals during criterion performance of the behavioral task. Both lesions produced disruption of behavioral discrimination in the form of increased error and intertrial responding. Granule cell discharges to the tone stimuli were disrupted by each type of lesion. Septal lesions reduced the differential discharge tendency to CS+ and CS- and changed granule cell firing on all trials to statistically resemble firing on CS- trials in normal animals. Extensive lesions in the entorhinal cortex or knife cuts that severed the perforant path caused near elimination of the tone-evoked discharges to both the CS+ and CS-tones. Septal and entorhinal lesions caused marked changes in the sequential dependence of the granule cell discharge compared with intact animals. Results are discussed in terms of the control of the granule cell discharge by the remaining afferent pathways in each type of lesion condition.

Acoustic Stimulation↗

Oxytocin augmentation of labor: a comparison of 15- and 30-minute dose increment intervals.

Two different regimens for oxytocin augmentation of labor were compared retrospectively in two institutions. In one regimen, the interval between dose increments was 15 minutes; in the other it was 30 minutes. All study patients were nulliparous and had uncomplicated pregnancies in spontaneous active labor; the 15-minute group consisted of 92 patients and the 30-minute group had 82 patients. No differences were demonstrated in age, dilation when oxytocin administration started, length of oxytocin administration, cesarean section rate, complications of delivery, birth weight, or Apgar scores. The maximal oxytocin dose in the 30-minute interval group was significantly lower. This group also had the oxytocin infusion stopped for evidence of uterine hyperstimulation and/or abnormal fetal heart rate tracing significantly less often (6.9% for the 30-minute interval versus 17.8% for the 15-minute interval; P = .0017). Overall, these results suggest that the longer interval does not increase the length of labor but decreases the incidence of uterine hyperstimulation.

Drug Administration Schedule↗