Biomedical subjects

T J Shors

Publications and source records attributed to T J Shors.

At least 19 recordsLinked to original sources

PubMed1995

Stress-induced sensitization and facilitated learning require NMDA receptor activation.

Exposure to an inescapable stressor facilitates acquisition of a classically-conditioned eyeblink response in the freely-moving rat. Here, we tested the hypothesis that the facilitation is mediated via activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor. Rats were injected with the competitive NMDA antagonist CGP-37849 (5 mg kg-1) or vehicle 2 h prior to exposure to restraint and 90, 1 mA, 1 s tail shocks. In contrast to the dramatic facilitation exhibited in stressed rats injected with the vehicle, rats whose NMDA receptors were blocked during exposure to the stressor did not exhibit any facilitation 24 h later. The antagonist alone had no effect on learning. These results demonstrate that the stress-induced facilitation of classical conditioning is dependent on NMDA receptor activation and support the hypothesis that stress is inducing a phenomenon similar in mechanism to that of long-term potentiation (LTP).

2-Amino-5-phosphonovalerate↗

PubMed1995

Enhanced glutamatergic neurotransmission facilitates classical conditioning in the freely moving rat.

Centrally active drugs that enhance alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-gated currents by increasing the amplitude and duration of fast, excitatory synaptic responses in the hippocampus have recently been described. The effects of the compound 1-(1,3-benzodioxol-5-ylcarbonyl) perperidine (BDP) on associative and non-associative aspects of the classically conditioned eyeblink response in the freely moving rat were examined. Rats injected with BDP blinked significantly more to an acoustic stimulus of 85 dB than did vehicle controls, indicating that the drug enhances alpha responding to discrete auditory cues. Using a less intense stimulus of 80 dB, rats injected with BDP did not exhibit alpha responding or pseudo-conditioning, yet learned the conditioned response at a facilitated rate. These results suggest that increasing excitatory neurotransmission enhances the processing of sensory information and may contribute to subsequent contingency detection.

Acoustic Stimulation↗

PubMed1994

Effect of stress and long-term potentiation (LTP) on subsequent LTP and the theta burst response in the dentate gyrus.

Exposure to an aversive and stressful event is reported to have similar effects on hippocampal plasticity and behavior as does exposure to high-frequency stimulation of the hippocampus. Here we directly compared the effects of exposure to a stressor vs. a previous induction of LTP on a subsequent induction of LTP and the extracellular response to a tetanus patterned after endogenous theta rhythms. Stimulating the dentate gyrus via the perforant path, Sprague-Dawley rats (n = 65) were tetanized 2 h after exposure to a stressor consisting of restraint and 60, 1, s, 1 mA tail shocks. Unstressed controls were tetanized once and then again 2 h later. Exposure to the stressor impaired LTP of the EPSP 2 h later, as did a previous induction of LTP. In addition, exposure to the stressor altered the extracellular response to subsequent theta burst stimulation (10, 40 ms bursts at 100 Hz, each separated by 200 ms), as did a previous induction of LTP. Whereas unstressed rats exposed to the first tetanus exhibited a marked decline in the amplitude across successive bursts, stressed rats exhibited no such decline, a response pattern similar to that observed in unstressed rats exposed to a second tetanus. The similarity between the effects of stress and tetanic stimulation on hippocampal plasticity support the hypothesis that stress and LTP are converging on similar neuronal mechanisms.

Animals↗

PubMed1994

Exposure to inescapable stress persistently facilitates associative and nonassociative learning in rats.

The present study examined the proactive effects of inescapable stress on aversive Pavlovian conditioning. Stressed rats were restrained and exposed to 90 1-mA tailshocks. Twenty-four hours later, all rats were exposed to 10 conditioned stimuli (CS; 350 ms of white noise at 85 dB). Rats then received either paired training in which the CS coterminated with a 100-ms, 0.7-mA periorbital shock or the same stimuli presented in an explicitly unpaired fashion. After the unpaired exposures, these rats were also exposed to paired training. Previously stressed rats exhibited persistent sensitization to the white-noise stimulus. Stressed rats exposed to unpaired stimuli, and no longer exhibiting a sensitized response, acquired the eyeblink conditioned response at a facilitated rate when these stimuli were presented in a paired fashion. These results also demonstrate that the effect of stress on classical conditioning is long-lasting, in excess of 48 hr.

Acoustic Stimulation↗

PubMed1992

Stress-induced facilitation of classical conditioning.

Stress has been shown to impair subsequent learning. To determine whether stress would impair classical conditioning, rats were exposed to inescapable, low-intensity tail shock and subsequently classically conditioned under freely moving conditions with a brief periorbital shock unconditioned stimulus and a white noise conditioned stimulus. Unexpectedly stressed rats exhibited significantly more conditioned eyeblink responses and the magnitude of their individual responses was also enhanced. These results stand in contrast to the learning deficits typically observed and suggest that stress can enhance the acquisition of discrete conditioned responses.

Acoustic Stimulation↗

PubMed1992

Long-term potentiation is associated with increased [3H]AMPA binding in rat hippocampus.

The location and nature of the changes underlying long-term potentiation (LTP) remain controversial issues. In this study, we tested the possibility that changes in binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA/quisqualate and N-methyl-D-aspartate (NMDA) subtype of glutamate receptors are associated with LTP. LTP was elicited in vivo by stimulation of the perforant pathway in anesthetized rats. One hour following stimulation the animals were sacrificed. We performed quantitative ligand binding autoradiography on frozen brain sections using [3H]AMPA and [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) to label the AMPA/quisqualate and the NMDA receptors, respectively. No changes in [3H]TCP binding were detected in any of the treatment groups. However, increases in [3H]AMPA binding were observed only in animals that exhibited LTP. These increases were bilateral and present in several subfields of the hippocampus and cortical areas. Administration of the NMDA receptor antagonist, ketamine, prior to tetanic stimulation prevented both the increase in binding and the induction of LTP. These results suggest that changes in the characteristics of AMPA/quisqualate receptors are a biochemical correlate of LTP.

Analysis of Variance↗

PubMed1992

Acute stress impairs (or induces) synaptic long-term potentiation (LTP) but does not affect paired-pulse facilitation in the stratum radiatum of rat hippocampus.

Rats were exposed to restraint coupled with 60, 1-sec, 1-mA, 60-Hz tail shocks. One hippocampus was immediately dissected for in vitro measurement of paired-pulse facilitation and LTP of the excitatory postsynaptic potential (EPSP) recording from the stratum radiatum of field CA1. There was no change in paired-pulse facilitation, suggesting that acute exposure to the stressor does not result in a decrease in presynaptic neurotransmitter release. There was, however, a significant decrease in the percent LTP produced by theta burst stimulation relative to naive controls. These results are consistent with the hypothesis that the stress-induced impairment of LTP is a result of changes in the postsynaptic glutamate receptors, specifically the AMPA type.

Animals↗

PubMed1992

Control of interocular suppression as a function of differential image blur.

This experiment studied normal adults, normal children, and corrected strabismics with alternating fixation, evaluating their ability to detect information presented to one eye under viewing conditions which might affect their eye preference. An apparatus was used which allowed unconstrained, binocular viewing of a video monitor, but in which the image seen by one eye was blurred while that seen by the other eye was in sharp focus. Under these viewing conditions, subjects were asked to identify a sharply focused letter which was shown briefly to the eye which was seeing the blurred background image or to the one which was watching the well-focused image. The question was whether there would be general suppression of the eye that was shown a degraded background, causing a reduction in its ability to process other information being presented. The results indicate no performance penalty for children, a mild decrement in recognition accuracy for normal adults, and a severe deficit in the ability of corrected strabismics to attend to the eye which views a blurred image. These results suggest that the loss of binocular vision that accompanies childhood strabismus is not a result of an inherent sensitivity to blurring, insofar as such vulnerability is reflected by these acute testing conditions.

Adolescent↗

PubMed1991

Increased synthesis of two polypeptides in area CA1 of the hippocampus in response to repetitive electrical stimulation.

Changes in the pattern of newly synthesized polypeptides were investigated in the in vitro hippocampal slice following exposure to repetitive stimulation with and without the induction of long-term potentiation. Using [35S]methionine labeling of polypeptides and two-dimensional gel electrophoresis, we detected an increase in the rate of synthesis of two polypeptides (48 kDa and 89 kDa) in CA1 in response to repetitive stimulation of the Schaffer collaterals. The synthesis of the 48 kDa polypeptide (pI approximately 6.6) increased 240% in response to high-frequency stimulation (100 Hz) relative to the same protein from unstimulated slices (n = 14), and increased 220% in response to low-frequency stimulation (1 Hz) (n = 5). Blockade of the N-methyl-D-aspartate (NMDA) receptor induced the protein 180%, with no further increase following tetanic stimulation. An 89 kDa doublet (pI approximately 6.8) increased 150% following high-frequency and 140% following low-frequency stimulation. Blockade of the NMDA receptor increased this protein as well (180% of the unstimulated control) and no further increase was observed following high-frequency stimulation. Based on physicochemical and electrophysiological properties, these proteins are not identifiable as any of those previously associated with long-term potentiation or repetitive electrical stimulation.

2-Amino-5-phosphonovalerate↗

PubMed1991

Selective increase of AMPA binding to the AMPA/quisqualate receptor in the hippocampus in response to acute stress.

The binding properties of ligands specific for two subclasses of glutamate receptors were studied by quantitative autoradiography after one hour of acute immobilization/shock stress. [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine (TCP) and [3H]alpha-amino-3-methylisoxazole-4-propionic acid (AMPA) were used to visualize the N-methyl-D-aspartate receptor and the AMPA/quisqualate receptor types, respectively. While no change was observed in the binding properties of the [3H]TCP, [3H]AMPA binding was significantly increased in several areas of the hippocampus of acutely stressed rats relative to naive controls.

Animals↗

PubMed1991

A negative correlation between the induction of long-term potentiation and activation of immediate early genes.

In the present study we examined the relationship between the induction of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats and activation of immediate early genes (IEGs; c-fos and zif/268) using several different high-frequency stimulation paradigms. Stimulation parameters that effectively induced LTP were not associated with IEG activation. Conversely, stimulation parameters that failed to induce LTP consistently resulted in IEG activation. These results suggest that there is a negative correlation between IEG activation and LTP, and that activation of IEGs is neither necessary nor sufficient for the induction of LTP.

Animals↗

PubMed1991

Activation of immediate early genes after acute stress.

We used in-situ hybridization to study the effect of acute stress on induction of the immediate early genes (IEGs), c-fos and zif/268, in the rat brain. After one hour of restraint plus intermittent tail shock, messenger RNA (mRNA) levels for both genes were significantly increased bilaterally in the neocortex, particularly in layers IV, V and VI, and in the CA1 region of the hippocampus. This regionally-specific response suggests that IEGs may have a role in the mediation of acute stress responses in the central nervous system.

Acute Disease↗

PubMed1990

Opioid antagonist eliminates the stress-induced impairment of long-term potentiation (LTP).

Rats (n = 20) were injected with the opioid antagonist naltrexone and half were exposed to inescapable shock/restraint. Another 20 rats were injected with saline and half were exposed to shock. Neither saline nor naltrexone alone had any effect on hippocampal LTP. A large reduction in LTP was observed in saline rats exposed to shock, while normal LTP developed in the naltrexone rats exposed to shock. Thus, naltrexone eliminated the impairment, and thereby implicated endogenous opioids in the mechanism responsible for the stress-induced impairment of LTP.

Action Potentials↗

PubMed1990

Unpredictable and uncontrollable stress impairs neuronal plasticity in the rat hippocampus.

Almost by definition, learning and the effect of stress on learning represent modifications of existing neuronal circuitry. Under some circumstances, this modification can be measured electrophysiologically. One such measure of plasticity is long-term potentiation (LTP), a long-lasting increase in synaptic efficacy following brief exposure to tetanic stimulation. In 1987, Foy et al. reported that hippocampal LTP was impaired by exposure to inescapable shock. We have recent evidence that the impairment in LTP can be prevented by allowing the animal to learn to escape the shock (Shors et al., 1989), indicating that the stress effect is to some extent mediated by "psychological" variables. Regardless of LTP's putative role in learning and memory processes, such a stress-induced decrease in neuronal plasticity is likely to have profound effects on the behaving organism.

Adaptation, Physiological↗

PubMed1990

Effect of adrenalectomy and demedullation on the stress-induced impairment of long-term potentiation.

In these three experiments, we investigated the effect of adrenalectomy and adrenal demedullation on the stress-induced impairment of long-term potentiation (LTP) in the rat hippocampal slice. In the first, adrenalectomy alone resulted in a significant reduction in LTP, while exposure to stress resulted in a further reduction. In the second, replacing corticosterone in adrenalectomized rats did not restore LTP. In the last experiment, demedullation resulted in a reduction in LTP similar to that induced by adrenalectomy, while exposure to stress did not result in a further reduction. In combination, these studies provide evidence that the adrenal medullary system modulates hippocampal plasticity and the stress-induced impairment of LTP.

Adrenal Glands↗

PubMed1989

Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus.

A group of rats was trained to escape low-intensity shock in a shuttle-box test, while another group of yoked controls could not escape but was exposed to the same amount and regime of shock. After 1 week of training, long-term potentiation (LTP) was measured in vitro in hippocampal slices. Exposure to uncontrollable shock massively impaired LTP relative to exposure to the same amount and regime of controllable shock. These results provide evidence that controllability modulates plasticity at the cellular-neuronal level.

Animals↗

PubMed1986

Recording pattern visual evoked potentials under chloral hydrate sedation.

Accurate assessment of visual function in infants and preverbal children is difficult because of the dependence on vision tests that require the patient's cooperation. In an attempt to resolve this problem, we evaluated pattern visual evoked potentials (PVEPs) obtained on infants under chloral hydrate sedation. Ten patients were studied--four with unilateral amblyopia, three with suspected amblyopia, and three without amblyopia. Patients with amblyopia showed robust and reproducible responses from the sound eye, while responses from the amblyopic eye were significantly diminished (amplitude ratio less than or equal to 0.63). The PVEP responses from patients without amblyopia were large in amplitude and symmetrical between fellow eyes (amplitude ratio greater than 0.9). In two eyes with normal vision, optically fogging the patterned stimulus image substantially reduced the PVEP response, establishing a sensitivity to pattern images rather than changes in the overall luminance. We have thus determined that the PVEP can be reliably obtained under chloral hydrate sedation and that these responses, like PVEP responses taken in the awake state, reflect the presence of amblyopia and image clarity. Use of the PVEP with chloral hydrate sedation may prove clinically useful for detecting amblyopia in uncooperative infants and children.

Amblyopia↗

PubMed1986

P100 amplitude variability of the pattern visual evoked potential.

This study quantifies the amplitude variability of the pattern visual evoked potential (P-VEP) and compares this variability between the two eyes and between individual runs recorded in the typical clinical laboratory. Cooperative adults were studied in order to obtain measurements under optimal conditions. Average P100 amplitudes of 10 runs for one eye were essentially equal to average P100 amplitudes of the other eye, as were the variances. Mean amplitude ratio (the smaller amplitude divided by the larger amplitude) was 0.91. With a group mean P100 amplitude of 10.06 microV, standard deviation for intrasubject data was 1.84, and for intersubject data was 3.75. Therefore, most of the amplitude variability between the two eyes is due to run-to-run variability. A minimum of 3 runs (100 stimuli each) and an optimum of 5 runs should be recorded before making an evaluation.

Adult↗