Search PubMed⌕ Search

Biomedical subjects

T C Foster

Publications and source records attributed to T C Foster.

At least 19 recordsLinked to original sources
PubMed2001

Examination of estradiol effects on the rapid estradiol mediated increase in hippocampal synaptic transmission in estrogen receptor alpha knockout mice.

Hippocampal slices from rats exhibit a rapid increase in basal synaptic transmission following 17 beta-estradiol (E(2)) application. In the current study we examined the role of the classic genomic receptor, estrogen receptor alpha (ER alpha), in mediating E(2) effects on synaptic transmission. E(2) (100 pM) increased the extracellular synaptic response in hippocampal slices from gonadectomized male and female mice lacking a functional ER alpha knockout (ER alpha KO) and wild-type (WT) littermates. No sexually dimorphic differences were observed, however, the increase in the field potential was more pronounced in WT mice. ER antagonists did not block E(2) mediated growth of the synaptic response in ER alpha KO mice. The results suggest that the rapid effect of E(2) on synaptic transmission is not mediated by ER alpha, however, ER alpha appears to modulate non-genomic influences on synaptic transmission.

Animals↗
PubMed2001

Calcineurin links Ca2+ dysregulation with brain aging.

Brain aging is associated with altered Ca(2+) regulation. However, many Ca(2+) signal transduction mechanisms have not been explored in the aged brain. Here, we report that cytosolic expression and activity of the Ca(2+)-dependent protein phosphatase calcineurin (CaN) increases in the hippocampus during aging. CaN changes were paralleled by increased activation, but not expression, of CaN-regulated protein phosphatase 1 and a reduction in the phosphorylation state of CaN substrates involved in cell survival (i.e., Bcl-2-associated death protein and cAMP response element-binding protein). The age-related increase in CaN activity was not attributable to the inability of CaN to translocate to the membrane and was reduced by blocking L-type Ca(2+) channels. Finally, increased CaN activity correlated with memory function as measured with the Morris water escape task. The results suggest that altered regulation of CaN is one of the processes that could link Ca(2+) dyshomeostasis to age-related changes in neural function and cognition.

Aging↗
PubMed2001

Mechanism for increased hippocampal synaptic strength following differential experience.

Exposure to novel environments or behavioral training is associated with increased strength at hippocampal synapses. The present study employed quantal analysis techniques to examine the mechanism supporting changes in synaptic transmission that occur following differential behavioral experience. Measures of CA1 synaptic strength were obtained from hippocampal slices of rats exposed to novel environments or maintained in individual cages. The input/output (I/O) curve of extracellularly recorded population excitatory postsynaptic potentials (EPSPs) increased for animals exposed to enrichment. The amplitude of the synaptic response of the field potential was related to the fiber potential amplitude and the paired-pulse ratio, however, these measures were not altered by differential experience. Estimates of biophysical parameters of transmission were determined for intracellularly recorded unitary responses of CA1 pyramidal cells. Enrichment was associated with an increase in the mean unitary synaptic response, an increase in quantal size, and a trend for decreased input resistance and reduction in the stimulation threshold to elicit a unitary response. Paired-pulse facilitation, the percent of response failures, coefficient of variance, and estimates of quantal content were not altered by experience but correlated well with the mean unitary response amplitude. The results suggest that baseline synaptic strength is determined, to a large extent, by presynaptic release mechanisms. However, increased synaptic transmission following environmental enrichment is likely due to an increase in the number or efficacy of receptors at some synapses and the emergence of functional synaptic contacts between previously unconnected CA3 and CA1 cells.

Action Potentials↗
PubMed2000

Novel effects of estradiol and estrogen receptor alpha and beta on cognitive function.

Estrogen influences the development of memory function in humans and rodents and can modulate memory in adults. In these studies we examined the role of the estrogen receptors alpha (ERalpha) and beta (ERbeta) in mediating performance on a hippocampal-dependent, hormone-sensitive task, inhibitory avoidance (IA). Ovariectomized (OVX) estrogen receptor-alpha-knockout (ERalphaKO) mice displayed impaired performance on the IA task and OVX heterozygotic (HET) mice exhibited performance that was intermediate between ERalphaKO and wild-type (WT) mice. Impaired performance by ERalphaKO mice was rescued by E(2) treatment. The ER antagonist, tamoxifen, did not block enhancement of retention by E(2) suggesting that E(2) mediated modulation of memory is not caused by known genomic receptor mechanisms. In contrast to ERalphaKO mice, IA performance by OVX estrogen receptor-beta-knockout (ERbetaKO) mice was not compromised. The results indicate an important role for ERalpha, relative to ERbeta, in the establishment of cognitive function and suggest that E(2) modulates memory function via a novel estrogenic mechanism.

Animals↗
PubMed2000

Receptor blockade reveals a correspondence between hippocampal-dependent behavior and experience-dependent synaptic enhancement.

This study examined the involvement of N-methyl-D-aspartate receptors (NMDARs) in experience-dependent synaptic plasticity. Rats chronically received an NMDA receptor antagonist (AP5) or saline (SAL) and were exposed to individual cages (IC) or environmental enrichment (EC). AP5 impaired measures of hippocampal-dependent behavior and increased locomotor activity. Perforant path synaptic strength, measured in the in vitro hippocampal slice, was increased and long-term potentiation (LTP) was decreased for EC+SAL animals. The experience-dependent effects on synaptic function were inhibited by drug treatment. Measures of synaptic strength were correlated with hippocampal-dependent behavior and synaptic plasticity for EC animals. The results suggest a relationship between hippocampal-dependent behavior and experience-dependent modification of perforant path synaptic function through NMDAR activation.

2-Amino-5-phosphonovalerate↗
PubMed1999

Sex with knockout models: behavioral studies of estrogen receptor alpha.

Estrogens are an important class of steroid hormones, having multiple targets, in the body and brain, and exerting ubiquitous effects on behavior. At present, two estrogen receptors (ERalpha and beta) have been cloned and sequenced in mammals. In the brain these receptors are regionally specific, but both have widespread distributions, which are largely non-overlapping. Given the newly emerging complexities of estrogen's mechanisms of action it is important to distinguish which pathways are involved in modifying which behaviors. We use a knockout mouse, lacking functional copies of the estrogen receptor alpha (ERalpha) gene, to study the mechanisms by which estrogens mediate behaviors. There are pronounced ramifications of ERalpha gene disruption on behavior. First, female ERalpha knockout (ERalphaKO) mice do not display normal feminine sexual behavior. Second, treatment of adult mice with androgens promotes masculine sexual behavior in both sexes. However, male-typical sexual behavior is severely compromised in male and female ERalphaKOs. Third, male ERalphaKOs do not exhibit the same social preferences for female mice as do wildtype (WT) littermates. Thus, the ERalpha is essential for normal expression of sexual behaviors. In addition, gonadectomized ERalphaKO and WT mice rapidly learn to escape from the Morris water maze. Exogenous estrogen treatment prevents WT females from learning this task, yet, has no effect in ERalphaKO mice, suggesting that estrogens effects on learning in adult females involves the ERalpha. Based on these data we hypothesize that ERalpha mediates many of the effects of estrogen on sexual behavior, learning, and memory.

Animals↗
PubMed1999

MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits.

Alterations in N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine whether NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24 months) and adult (3-6 months) male Fischer 344 rats received 18 training trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial was administered to assess the acquisition of spatial bias, which was determined by the percent of time spent in the goal quadrant and the number of platform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (+)-10, 11-dihydro-5methyl-5H-dibenzo(a,b)cycloheptene-5,10 imine (MK-801, 0. 05 mg/kg, i.p.), or a vehicle injection of equal volume. Approximately 24 h later, rats were administered a second free-swim probe trial to assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the aged rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, suggesting that NMDAR activity may be involved in rapid forgetting during aging. Because blockade of NMDARs also may impair new learning, which may, in turn, protect previously stored information from retroactive interference, rats in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine did not enhance retention in the aged group, consistent with the hypothesis that MK-801 influenced memory in aged rats through its actions on NMDAR-dependent synaptic plasticity.

Aging↗
PubMed1999

Involvement of hippocampal synaptic plasticity in age-related memory decline.

This article examines the functional significance of Ca(2+)-dependent synaptic plasticity in relation to compromised memory function during aging. Research characterizing an age-related decline in memory for tasks that require proper hippocampal function is summarized. It is concluded that aged animals possess the mechanisms necessary for memory formation, and memory deficits, including rapid forgetting, result from more subtle changes in memory processes for memory storage or maintenance. A review of experimental studies concerning changes in hippocampal neural plasticity over the course of aging indicates that, during aging, there is a shift in mechanisms that regulate the thresholds for synaptic modification, including Ca(2+) channel function and subsequent Ca(2+)-dependent processes. The results, combined with theoretical considerations concerning synaptic modification thresholds, provide the basis for a model of age-related changes in hippocampal synaptic function. The model is employed as a foundation for interpretation of studies examining therapeutic intervention in age-related memory decline. The possible role of altered synaptic plasticity thresholds in learning and memory deficits suggests that treatments that modify synaptic plasticity may prove fruitful for the development of early therapeutic interventions in age-related neurodegenerative diseases.

Aging↗
PubMed1998

AMPA receptor properties in adult rat hippocampus following environmental enrichment.

In adult rats, environmental enrichment has been shown to selectively increase -AMPA binding in the hippocampus but the molecular mechanisms underlying this effect remain unknown. We used in situ hybridization with antisense oligonucleotides to determine possible changes in the hippocampal expression of messenger RNAs for different subunits of AMPA receptors in adult rats following exposure to an enriched environment. Quantitative analysis revealed that mRNA levels for three subtypes of AMPA glutamate receptors (GluR1-3; Flip and Flop variants) were not modified in any hippocampal region after environmental enrichment. In addition, no differences were detected in the levels of GluR1 and GluR2/3 proteins in Western blots of hippocampal membranes from enriched rats. Nevertheless, quantitative ligand binding autoradiography indicated that environmental enrichment evoked a significant and uniform decrease in the capacity of calcium or phosphatidylserine (PS) to up-regulate -AMPA binding in various hippocampal regions but not in the cerebral cortex. These findings support previous observations suggesting that post-translational changes in AMPA receptor properties, as a result of the activation of calcium-dependent processes, may represent an important mechanism underlying long-term modifications of synaptic efficacy in the rat hippocampus.

Animals↗
PubMed1998

GABA(b) receptors differentially regulate hippocampal CA1 excitatory synaptic transmission across postnatal development in the rat.

Depression of excitatory postsynaptic potentials (EPSPs) by the GABA(b) agonist, baclofen, was compared in hippocampal slices from juvenile (postnatal day (P) 15-21) and young adult (P28-35) rats. EPSP inhibition following baclofen application was not different between age groups, however, paired-pulse facilitation (PPF) increased more in young adults relative to juveniles. The differential effect of baclofen on PPF was not due to tonic receptor activity, since the GABA(b) antagonist, saclofen, did not differentially modify PPF. The baclofen-mediated increase in PPF for juvenile slices could be enhanced by first increasing transmitter release through an increased bath Ca2+ concentration. These findings suggests that ligand-mediated presynaptic depression is inversely related to the level of transmitter release and maturation of presynaptic inhibition is related to development of release.

Analysis of Variance↗
PubMed1998

Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels.

The role of L-type Ca2+ channels in the induction of synaptic plasticity in hippocampal slices of aged (22-24 months) and young adult (4-6 months) male Fischer 344 rats was investigated. Prolonged 1 Hz stimulation (900 pulses) of Schaffer collaterals, which normally depresses CA3/CA1 synaptic strength in aged rat slices, failed to induce long-term depression (LTD) during bath application of the L-channel antagonist nifedipine (10 microM). When 5 Hz stimulation (900 pulses) was used to modify synaptic strength, nifedipine facilitated synaptic enhancement in slices from aged, but not young, adult rats. This enhancement was pathway-specific, reversible, and impaired by the NMDA receptor (NMDAR) antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Induction of long-term potentiation (LTP) in aged rats, using 100 Hz stimulation, occluded subsequent synaptic enhancement by 5 Hz stimulation, suggesting that nifedipine-facilitated enhancement shares mechanisms in common with conventional LTP. Facilitation of synaptic enhancement by nifedipine likely was attributable to a reduction ( approximately 30%) in the Ca2+-dependent K+-mediated afterhyperpolarization (AHP), because the K+ channel blocker apamin (1 microM) similarly reduced the AHP and promoted synaptic enhancement by 5 Hz stimulation. In contrast, apamin did not block LTD induction using 1 Hz stimulation, suggesting that, in aged rats, the AHP does not influence LTD and LTP induction in a similar way. The results indicate that, during aging, L-channels can (1) facilitate LTD induction during low rates of synaptic activity and (2) impair LTP induction during higher levels of synaptic activation via an increase in the Ca2+-dependent AHP.

Aging↗
PubMed1998

Late developmental changes in the ability of adenosine A1 receptors to regulate synaptic transmission in the hippocampus.

Paired-pulse facilitation (PPF) of CA3-CA1 excitatory postsynaptic potentials (EPSP) was compared in hippocampal slices from juvenile (postnatal day (P) 15-21) and young adult rats (P28-P35) following application of adenosine. Relative to juveniles, young adults expressed an increase in baseline synaptic strength that was accompanied by a decrease in PPF suggesting a developmental increase in transmitter release. While adenosine depressed the EPSP slope to a similar extent in juveniles and young adults, PPF increased during adenosine application only for young adults. The differential effect of adenosine on PPF was not due to differences in receptor function or in extracellular ligand levels, since the A1 antagonist cyclopentyltheophylline (CPT) did not differentially affect PPF across age. Adenosine could increase PPF in juvenile slices under conditions of enhanced transmitter release, through an increase in the bath Ca2+ concentration, or addition of forskolin to the bath. These data indicate that the ability to modify synaptic transmission through presynaptic adenosine A1 receptors increases across postnatal development with the maturation of release mechanisms.

Aging↗
PubMed1998

Sex differences in the activational effect of ERalpha on spatial learning.

This study investigated the role of the estrogen receptor alpha (ERalpha) in mediating performance on a spatial discrimination task, the Morris water maze. Spatial discrimination on this water escape task was examined in eight groups of gonadectomized mice. Male and female wild-type (WT) and littermate mice lacking functional copies of the ERalpha gene (ERalphaKO), were treated with estradiol benzoate (EB) or sesame oil vehicle. Subjects were trained on the water escape task over a 4-day period (four trials per block, three blocks per day). Latency to find the hidden platform was measured. Only female WT mice treated with EB failed to learn this spatial discrimination task. All males, WT and ERalphaKO treated with EB or oil exhibited decreased latencies across blocks of trials, WT females treated with oil, and ERalphaKO females, regardless of treatment, learned the spatial discrimination task. In order to eliminate motivational or sensory-motor impairments as a factor in describing the poor spatial discrimination performance of WT females treated with EB, the cue version of the water maze task was employed. Results from the cue phase of the task indicate that EB and oil-treated WT females exhibited a similar decrease in escape latencies across blocks of trials, indicating good cue discrimination performance. Taken together, the results indicate that ERalpha activation impairs acquisition of spatial discrimination of the water escape task, but not cue discrimination, in female mice. Because ligand-bound ERalpha appears to operate differently in male and female mice we hypothesize that the ability of ERalpha to affect learning is organized during development.

Animals↗
PubMed1998

Alterations in the balance of protein kinase/phosphatase activities parallel reduced synaptic strength during aging.

The current research examined the regulation of synaptic strength by protein phosphorylation during aging. Bath application of the protein phosphatase 1 and 2A (PP1 and PP2A) inhibitor calyculin A (1 microM) enhanced CA3-CA1 synaptic strength in hippocampal slices from aged male (20-24 mo) but not from young adult male (4-6 mo) Fischer 344 rats. Similarly, injection of the PP1 and PP2A inhibitor microcystin-L,R (5 microM) into CA1 cells caused an increase in the intracellular synaptic response only in slices from aged rats. In contrast, bath application of the serine/threonine kinase inhibitor H-7 (10 microM) induced a decrease in synaptic strength only in slices from the young adult group. These results demonstrate that phosphorylation dependent regulation of intrinsic synaptic efficacy changes during aging.

Aging↗
PubMed1997

Insensitivity of the hippocampus to environmental stimulation during postnatal development.

Development of cortical sensory systems is influenced by environmental experience during "sensitive periods," before onset of behavioral function. During these periods, synaptic plasticity is observed, and neuronal function shows increased responsiveness to environmental stimulation. Because the hippocampus is late to develop, and because it demonstrates synaptic plasticity before the onset of behavioral function, this experiment was designed to determine whether, like the sensory cortices, the hippocampus undergoes a period of enhanced responsiveness to the environment. Rats at three ages [postnatal day 16 (P16), P23, and P30] were tested on a hippocampally dependent task, spontaneous alternation, and exposed to a novel environment. They were then killed and processed for immunocytochemistry to Fos or for in vitro electrophysiology in hippocampal area CA1. Age-matched control subjects were killed immediately after removal from the home cage. Spontaneous alternation was only observed in the oldest (P30) animals. In these same animals, the environmental manipulation resulted in an increase in Fos-like immunoreactivity (FL-IR), relative to controls, and a decrease in the ability to induce long-term potentiation (LTP). In P16 and P23 animals, the environmental manipulation resulted in no differences in hippocampal FL-IR or LTP. These results suggest that, rather than showing increased responsiveness to the environment at these ages, the hippocampus is environmentally insensitive and that it is isolated from the effects of environmental stimuli. The hippocampus, a neural region important for higher cognitive function, may develop via a mechanism different from those observed in the primary sensory cortices.

Aging↗
PubMed1997

Development of metabotropic glutamate receptor-mediated synaptic inhibition.

Modulation of hippocampal CA3-CA1 synaptic transmission during metabotropic glutamate receptor (mGluR) activation was investigated in juvenile (postnatal day (P) 15-21) and young adult rats (P28-35). The mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD) depressed the EPSP slope more in young adults than juveniles. ACPD increased paired-pulse facilitation (PPF) at both ages. The group I mGluR antagonist (+)-alpha-methylcarboxyphenylglycine (MCPG) inhibited the ACPD-mediated depression of the EPSP slope and completely blocked the increase in PPF only in young adults. Minimal effects of MCPG on ACPD-dependent synaptic depression were observed in juveniles. These data suggest that presynaptic group I mGluR-mediated synaptic inhibition increases across late postnatal development. In addition, other mGluR subtypes, with the ability to depress presynaptic function, appear to be present in juveniles.

Animals↗
PubMed1997

Mitral/tufted cell activity is attenuated and becomes uncoupled from respiration following naris closure.

Patterned neural activity helps to establish neuronal connectivity, produce coding of sensory information, and shape synaptic strengths. Here we demonstrate that normal olfactory bulb development might rely on spatial and temporal patterns of afferent neural activity. Neonatal naris occlusion profoundly impacts the development of the ipsilateral olfactory bulb, including reduced bulb volume, decreased protein synthesis, and increased cell death. Relatively few morphologic changes occur if closure is performed postweaning. We examined the immediate electrophysiological consequences of occlusion across this developmentally sensitive period by recording spontaneous and odor-driven mitral/tufted cell responses while the naris was open, closed, and then reopened. In 1-week-old animals, occlusion severely attenuated spontaneous activity, and presentation of the broad-spectrum odorant amyl acetate failed to evoke responses. In 2- and 4-week old rats, spontaneous activity was also reduced by naris closure. However, some cells remained responsive to concentrated odors, even in animals with transected anterior commissures, suggesting passage of odors across the septal window or retronasal pathways. In all age groups, cellular activity became uncoupled from the respiratory cycle. Approximately 47% (18 of 38) of the mitral/tufted cells exhibited activity that was correlated with respiration in the open-naris state, while only 5% (2 of 38) were coupled during naris closure. These data (a) indicate that naris closure reduces both spontaneous and odor-evoked responses, and (b) provide an electrophysiological correlate to a sensitive period in bulb development. The loss of respiration-related synchrony and the reduced activity of mitral/tufted cells may synergistically contribute to the diverse consequences of naris closure on bulb development.

Animals↗