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Biomedical subjects

R F Thompson

Publications and source records attributed to R F Thompson.

At least 109 records · Page 6Linked to original sources

Are memory traces localized or distributed?

Evidence supports the view that "memory traces" are formed in the hippocampus and in the cerebellum in classical conditioning of discrete behavioral responses (e.g. eyeblink conditioning). In the hippocampus, learning results in long-lasting increases in excitability of pyramidal neurons that appear to be localized to these neurons (i.e. changes in membrane properties and receptor function). However, these learning-altered pyramidal neurons are distributed widely throughout CA3 and CA1. Although it plays a key role in certain aspects of classical conditioning, the hippocampus is not necessary for learning and memory of the basic conditioned responses. The cerebellum and its associated brain stem circuitry, on the other hand, does appear to be essential (necessary and sufficient) for learning and memory of the conditioned response. Evidence to date is most consistent with a localized trace in the interpositus nucleus and multiple localized traces in cerebellar cortex, each involving relatively large ensembles of neurons. Perhaps "procedural" memory traces are relatively localized and "declarative" traces more widely distributed.

Animals↗

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↗

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↗

Differential effects of ketamine and MK-801 on the induction of long-term potentiation.

Ketamine and MK-801 are phencyclidine (PCP)-like noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor that produce a use-dependent blockade of the NMDA receptor-coupled channel. Recent studies have suggested that the binding properties of these drugs to the NMDA receptor in-vitro are different. In the present study, the effects of ketamine and MK-801 on the induction of long-term potentiation (LTP) were compared at perforant path--granule cell synapses in anaesthetized rats. LTP was observed in animals treated with either saline or MK-801, but not in those treated with ketamine. These results reveal that ketamine and MK-801 differentially modulate the induction of LTP, and we propose that this differential modulation may be related to the different binding properties of the drugs.

Animals↗

Effects of lidocaine injection in the interpositus nucleus and red nucleus on conditioned behavioral and neuronal responses.

The role of the cerebellum and the red nucleus in the conditioned eyeblink response was assessed, using a combination of reversible lesions and multiple-unit extracellular recording in the awake, behaving rabbit. Lesion, recording, and stimulation experiments have indicated that both of these structures are involved in the performance of learned skeletal muscle responses. The present study sought to distinguish the relative contributions of the interpositus nucleus and the red nucleus to the expression of the learned response by recording behavior-related multiple unit activity in one structure while reversibly inactivating the other via injections of local anesthetic. Results indicate that inactivating either the interpositus or the red nucleus temporarily abolishes the learned eyeblink response. Injection of lidocaine into the interpositus also abolishes the neuronal unit model of the conditioned response in the red nucleus, while injection into the red nucleus does not affect the model in the interpositus. These results are consistent with the hypothesis that the red nucleus acts as a relay for motor commands from the cerebellum, and that the plasticity that generates conditioned responses occurs in the cerebellum or an afferent structure.

Animals↗

Neural mechanisms of classical conditioning in mammals.

Evidence supports the view that 'memory traces' are formed in the hippocampus and in the cerebellum in classical conditioning of discrete behavioural responses. In the hippocampus learning results in long-lasting increases in excitability of pyramidal neurons that resemble the phenomenon of long-term potentiation. Although it plays a role in certain aspects of conditioning, the hippocampus is not necessary for learning and memory of the basic conditioned responses. The cerebellum and its associated brain-stem circuitry, on the other hand, does appear to be essential (necessary and sufficient) for learning and memory of the conditioned response. Evidence to date supports the view that mossy fibre convey conditioned stimulus information and that climbing fibres conveys the critical 'reinforcement' information to the cerebellum and that 'memory traces' appear to be formed in cerebellar cortex and interpositus nucleus.

Animals↗

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↗

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↗

Foci of increased T2 signal intensity in MR images of healthy elderly subjects. A follow-up study.

An 18-month follow-up study was conducted on 26 healthy elderly subjects with and without foci of increased T2 signal intensity on MR imaging. The subjects did not differ with respect to health status or cognitive performance as measured by the Cognitive Subscale of the Cambridge Mental Disorders of the Elderly Examination and the Mini Mental State Examination at follow-up. There was a significant decline in performance on the Digit Symbol Substitution Test in subjects who had evidence of T2 foci compared to the performance of subjects without T2 foci. This may indicate that the presence of T2 foci is correlated with subtle difficulties in learning and memory.

Aged↗

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↗

Treadmill exercise electrocardiography in the elderly with physical impairments.

Treadmill testing (TMT) was performed on 76 frail but ambulatory subjects, between 64 and 84 years of age, who had common health problems contributing to physical limitations but had no clinically apparent heart disease. The subjects achieved a mean symptom-limited maximal heart rate of 140.1 +/- 2.07 (SEM) beats per minute which was 80.2 +/- 2.1% of the predicted maximum for age. By standard criteria, ischemic responses were noted in only 5 subjects (6.6%). Three responses were categorized as inconclusive (multifocal ventricular ectopy, chest pain without electrocardiographic change, and prompt ST depression upon standing). TMT was well tolerated, with no significant difficulties encountered. Even for those frail elderly with diseases and physical impairments, symptom-limited TMT may be used with low risk to quantify functional capacity and for exercise prescription. Attempts to screen more intensively for cardiac disease may be irrelevant to their immediate need for maintaining function.

Aged↗

Orbital hemorrhage during ethmoid sinus surgery.

Orbital hemorrhage is an unusual complication of ethmoid surgery. A case of intraoperative orbital hemorrhage occurring during a medial maxillectomy and one occurring during a transethmoid sphenoidotomy are presented. The pathogenesis of this potentially serious complication is discussed. A sequential treatment algorithm is presented, consisting of medial orbitotomy, lateral canthotomy and inferior cantholysis, and inferior orbital decompression, along with concomitant medical management with mannitol, acetazolamide, and dexamethasone.

Acetazolamide↗

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↗

Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus.

Classical conditioning of skeletal muscle responses was accomplished by pairing microstimulation of the pontine nuclei as a conditioned stimulus (CS) with microstimulation of the dorsal accessory olive as an unconditioned stimulus (US). A conditioned response identical in form to the behavioral response elicited by the olivary stimulation was established when the CS was forward paired with the US, and behavioral extinction occurred with CS-alone presentations or unpaired CS-US presentations. Conditioned responding could not be established or maintained when the CS and US were simultaneously presented or when the US preceded the CS (i.e., backward paired). Complete lesions of the interpositus nucleus abolished both conditioned and unconditioned responses. These findings support the idea that plasticity associated with classical conditioning of skeletal muscle responses occurs in regions of the cerebellum that receive convergent CS and US input.

Animals↗

Classical discrimination conditioning of the rabbit's eyelid response using pontine stimulation as a conditioned stimulus.

Classical discrimination conditioning of the nictitating membrane/eyelid response was performed on seven rabbits using stimulation of the pontine nuclei or middle cerebellar peduncle as the conditioned stimulus (CS) and an air puff as the unconditioned stimulus (US). The rabbits learned to discriminate between a CS paired with a US and delivered to one pontine nucleus (the CS+) and a CS presented alone and delivered to the contralateral pontine nucleus (the CS-). Subsequent reversal of the discrimination was also achieved when the CS+ and CS- stimulation sites were interchanged. The results are interpreted as support for the idea that essential plasticity for classical eyelid conditioning occurs efferent to the pontine nuclei, possibly in regions of the cerebellum.

Animals↗

Stimulation of the lateral septum is a more effective conditioned stimulus than stimulation of the medial septum during classical conditioning of the eye-blink response.

Eight rabbits were trained in the classically conditioned eye-blink response procedure using stimulation of the septal nuclei as the conditioned stimulus (CS). Each rabbit was trained with both medial septal stimulation and lateral septal stimulation. Stimulation of the medial septum was a far less effective CS than stimulation of the lateral septum. This effect may be due to the different roles of these two nuclei in classical conditioning. Conditioning using lateral septal stimulation as a CS is dependent on the cerebellar interpositus nucleus as is conditioning using peripheral and other brain stimulation CSs.

Animals↗