Biomedical subjects

R F Thompson

Publications and source records attributed to R F Thompson.

At least 19 recordsLinked to original sources

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

Effects of the novel NMDA receptor antagonist, CGP 39551, on field potentials and the induction and expression of LTP in the dentate gyrus in vivo.

The effects of the novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist, CGP 39551 [the carboxyethylester of CGP 37849; DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid], on extracellular field potentials and long-term potentiation (LTP) induced in the dentate gyrus by stimulation of the perforant path were studied in anesthetized rats. CGP 39551 attenuated the population spike (PS) and excitatory postsynaptic potential (EPSP) amplitude of dentate field potentials, reduced the NMDA receptor-mediated component of train-evoked burst potentials, and prevented the induction of LTP. The decrease in PS and EPSP amplitude produced by CGP 39551 was observed mainly in non-potentiated synaptic populations; potentiated field potentials were only minimally affected by drug treatment. These results are consistent with receptors may contribute in a tonic manner to the state of dentate granule cell excitability. Finally, the differential modulation of potentiated and non-potentiated synapses by CGP 39551 suggests that a change in some properties of postsynaptic AMPA receptors is involved in the expression of LTP.

2-Amino-5-phosphonovalerate↗

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 rabbit nictitating membrane movements. I. A computer model of the retractor bulbi muscle and the associated orbital mechanics.

Our objective in this study is to synthesize existing experimental data by constructing a realistic neuromechanical control model of rabbit nictitating membrane (NM) movements. We model the retractor bulbi muscle at the motor unit level because this is the level of nervous system control and also facilitates comparison with experimental data. Our motor unit model is derived from an earlier model of muscle activation based on calcium kinetics and includes a post-activation potentiation mechanism. Motor units are combined into a model of whole muscle that includes length-tension and force-velocity effects. Finally, we incorporate the muscle model into a biomechanical model in which the globe and NM are represented as a system of inertial, viscous, and elastic elements. The model takes patterns of neural signals (in the form of impulses) as input and produces movement of the NM as output. Our muscle model quantitatively accounts for data on isometric force development and decay for twitch, double shock, and tetanic stimulation. The complete model may be used for analysis of the relationship of motoneuron activity to behavior or as a realistic response generator in models of NM conditioning. This study also highlights gaps in the experimental data on the rabbit NM effector system.

Animals↗

PubMed1992

Control of rabbit nictitating membrane movements. II. Analysis of the relation of motoneuron activity to behavior.

The objective of this study is to understand more precisely the relationship of motoneuron activity to movements of the rabbit nictitating membrane (NM). We use a model of the oculomotor plant to investigate what NM movements are generated by a given pattern of neural input and what inputs are required to generate particular NM movements. Simulated peak NM extensions can occur well over 50 ms after the end of motoneuron activity. The neural input required for the model to generate full amplitude NM extension responses is more consistent with single accessory abducens unit recordings from awake rabbits than recordings from anesthetized rabbits. An initial high frequency burst of neural activity followed by a rapid decay is required for simulations of conditioned responses (CRs) trained at a 125 ms interstimulus interval (ISI). For CRs trained with a 250 ms ISI, a more slowly rising and decaying neural activity is required. Model simulations show that the linear correlation between the shape of histogrammed motoneuron activity and the shape of NM movements can be high for long duration responses (> 400 ms) but is low for short duration responses (< 200 ms). Simulations are also consistent with the hypothesis that NM retraction is generally passive.

Animals↗

PubMed1992

Learning of a hippocampal-dependent conditioning task changes the binding properties of AMPA receptors in rabbit hippocampus.

The N-methyl-D-asparate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtypes of glutamate receptors have been shown to play critical roles in various forms of synaptic plasticity (i.e., learning and memory, long-term potentiation). We previously demonstrated that the binding of [3H]AMPA to the AMPA subtype of glutamate receptors was selectively increased in hippocampus following classical conditioning of the rabbit nictitating membrane response in a delay paradigm. We report here that the same effect was observed in a variant of this learning paradigm that requires the participation of the hippocampus, i.e., trace conditioning of the rabbit nictitating membrane. The binding of [3H]TCP (N-[1-(2-thienyl)cyclo-hexyl]-3,4-piperidine) to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of conditioned and unconditioned stimuli resulted in an increased binding of [3H]AMPA, an agonist of the AMPA receptors, in several hippocampal subfields while the binding of an antagonist, [3H]CNQX (6-nitro-7-cyanoquinoxaline-2,3-dione), was decreased. The results suggest that the learning-induced changes in binding of the ligands to the AMPA receptor reflect changes in affinity of the receptor rather than in the number of sites. These results support the hypothesis that changes in hippocampal glutamate receptors are a corollary of synaptic plasticity in certain forms of learning.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1992

BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity.

Brain-derived neurotrophic factor (BDNF) mRNA expression was studied in the hippocampus at various developmental stages in normal rats and following kainic acid (KA)-induced seizure activity. Systemic administration of KA strongly elevated BDNF mRNA levels in all hippocampal subregions after postnatal day 21. In contrast, even though KA induced intense behavioral seizure activity at postnatal day 8, the seizures were not associated with elevations of BDNF mRNA levels, indicating a clear dissociation between behavioral seizures and increases in BDNF mRNA levels and contradicting the view that BDNF mRNA expression is principally regulated by neuronal activity. In the dentate gyrus at postnatal day 13, intense BDNF mRNA expression was limited to a defined area at the border between granule cell and molecular layers, suggesting the possibility that segregation of BDNF mRNA into defined subcellular compartments may play a role in establishing the well-delineated patterns of innervation in the hippocampus.

Animals↗

PubMed1992

Memory.

The key interrelated issues in the neurobiology of memory are to identify the neural circuitries essential for memory formation, localize sites of memory storage and analyze mechanisms of memory formation, storage and retrieval. Several circuits have now been identified in vertebrates and researchers are investigating their properties, in particular the role of glutamate receptors and long-term potentiation, in memory formation. Invertebrate preparations continue to be of value and recent studies suggest that changes in gene expression and protein synthesis may be important in long-term sensitization.

Animals↗

PubMed1992

Conditioning using a cerebral cortical conditioned stimulus is dependent on the cerebellum and brain stem circuitry.

Electrical stimulation of the auditory cortex (AC) was used as a conditioned stimulus (CS) in the rabbit conditioned eyeblink preparation to trace the functional anatomical connections between the AC and the circuitry underlying this conditioned response. Conditioning was shown to be dependent on the cerebellar interpositus nucleus and the pontine nuclei (PN), structures that are essential for conditioning using a peripheral CS. The results suggest that the cerebellum and associated brain stem circuitry are a necessary part of the memory trace circuit for the conditioned eyeblink response, even when the cerebral cortex is artifically engaged as a CS by electrical stimulation. The results also suggest that the PN are a site of convergence between the CS circuit subserving classical conditioning for peripheral stimuli and the AC, and may therefore be a site where the AC can modulate more elaborate forms of conditioning.

Animals↗

PubMed1992

Cerebellar stimulation as an unconditioned stimulus in classical conditioning.

Rabbits were implanted with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone conditioned stimulus (CS), produced learning comparable to that seen with peripheral unconditioned stimuli (USs). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS-US trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS-US preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses.

Animals↗

PubMed1992

Phospholipase A2-induced changes in AMPA receptor: an autoradiographic study.

The expression of long-term potentiation and learning of a classical conditioning task increase [3H]-AMPA binding in hippocampus. Phospholipase A2 (PLA2) has been proposed to underly these changes, as PLA2 treatment of membrane preparations increases the affinity of AMPA receptors for agonists. We demonstrate here that preincubation of thin (10 microns) frozen rat brain sections with exogenous PLA2 and calcium at physiological temperature changes the binding properties of AMPA receptors. Quantitative autoradiography reveals that PLA2-treatment produces a differential increase in [3H]-AMPA binding across brain regions. The same treatment also decreases the binding of an antagonist ([3H]-CNQX) throughout the brain. We propose that PLA2 treatment results in a modification of the AMPA receptors which is regionally specific, probably due to different AMPA receptor subunit compositions.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1992

Disruption of classical eyelid conditioning after cerebellar lesions: damage to a memory trace system or a simple performance deficit?

Over the past 10 years, a number of laboratories have reported that classically conditioned skeletal muscle responses, such as conditioned nictitating membrane/eyelid responses, are critically dependent on activity in the cerebellum. For example, unilateral lesions of the cerebellar interpositus nucleus have been shown to prevent acquisition and abolish retention of the conditioned eyelid response on the side ipsilateral to the lesions without affecting conditioned responding (CR) on the contralateral side. Also, recording studies involving the interpositus nucleus have consistently revealed patterns of neuronal discharge that predict execution of the CR. The lesion and recording studies have generally been cited as evidence that plasticity in the cerebellum is critically involved in the learning and memory of classically conditioned responses. This interpretation was recently challenged by Welsh and Harvey (1989a), who claimed that cerebellar lesions simply produced a performance deficit and speculated that the role of the cerebellum was not in learning and memory processes associated with the CR but only in performance of the eye blink response. Presented here are three experiments that provide additional strong evidence for a critical role of the cerebellum in the learning and memory of the Pavlovian CR. These experiments include (1) demonstrations of complete and permanent CR abolition after appropriate interpositus lesions, (2) a failure to find systematic or persisting decrements in the unconditioned response amplitude (i.e., the eye blink reflex) after appropriate interpositus lesion, and (3) observations of differential effects on the CR and unconditioned response after lesions were placed in populations of motoneurons responsible for executing the eye blink response. These data are discussed in the context of performance versus learning issues; evidence presented here rules out the possibility that interpositus lesion abolition of the eye blink CR is simply due to lesion effects on performance.

Animals↗

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

Classical conditioning selectively increases AMPA receptor binding in rabbit hippocampus.

The NMDA and AMPA receptors have been shown to play critical roles in various forms of synaptic plasticity (learning and memory, long-term potentiation). The present study investigated the involvement of these two receptors in a well-characterized classical conditioning paradigm. Following classical conditioning of the rabbit nictitating membrane the binding properties of these two subclasses of excitatory amino acid transmitter receptors were analyzed in dorsal hippocampi by quantitative autoradiography. [3H] TCP and [3H] AMPA were used to identify the NMDA and AMPA receptors, respectively. The binding of [3H]TCP to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of the conditioned and unconditioned stimuli resulted in increased [3H] AMPA binding to the AMPA receptor in several subfields of the hippocampus, while unpaired presentations had no significant effects. The increase in binding was due to an increased affinity of the low-affinity component of the AMPA receptor. The results support the hypothesis that changes in glutamate receptors participate in the synaptic plasticity involved in certain forms of learning.

Animals↗

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

Are eyeblink responses to tone in the decerebrate, decerebellate rabbit conditioned responses?

Bloedel and associates recently claimed to have established conditioned eyeblink responses in the acute decerebrate, decerebellate rabbit. Their training procedure was extreme massed practice (mean intertrial interval of 9 s) and they used an idiosyncratic definition of the conditioned response (10% or more of the unconditioned response amplitude). They did not measure or control the excitability of their preparations and did not run any separate control groups for alpha responses, alpha conditioning or pseudoconditioning. Using normal animals we compared their training procedure with procedures standard in the field and analyzed the consequences of their scoring procedure. Our group trained at a 30-s intertrial interval (ITI) showed clear learning in the training session. In marked contrast, 3 groups trained at a 9-s ITI developed no conditioned responses. We also found that the method of scoring used by Bloedel and associates counts many spontaneous responses as conditioned responses (CRs) if unconditioned response (UR) amplitudes are low, excludes genuine CRs if UR amplitudes are high and does not control for the occurrence of spontaneous responses. It must therefore be concluded that the eyeblink responses to tone reported by Bloedel and associates to occur in the decerebrate, decerebellate rabbit are not associative CRs as they develop in the normal animal.

Animals↗

PubMed1991

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↗