Biomedical subjects

Bernard G Schreurs

Publications and source records attributed to Bernard G Schreurs.

10 recordsLinked to original sources

PubMed2006

Characteristics of IA currents in adult rabbit cerebellar Purkinje cells.

Classical conditioning the rabbit nictitating membrane involves changes in synaptic and intrinsic membrane properties of cerebellar Purkinje cell dendrites, and a 4-aminopyridine (4-AP)-sensitive potassium channel underlies these membrane properties. We characterized I(A) currents in adult, rabbit Purkinje cells to determine whether I(A) is the target channel involved in learning. Whole-cell recordings of Purkinje cell somas and dendrites revealed a fast activating and inactivating current with half maximal activation at -27.08 +/- 3.48 mV and -25.51 +/- 1.15 mV in somas and dendrites, respectively; half maximal inactivation at -58.91 +/- 2.34 mV and -49.90 +/- 2.58 mV; and a recovery time constant of 22.81 +/- 1.92 ms and 16.60 +/- 4.26 ms. Outside-out patch recordings from cerebellar Purkinje cell somas confirmed these 4-AP-sensitive currents with half maximal activation at -13.85 +/- 1.17 mV and half maximal inactivation at -55.07 +/- 5.54 mV. More importantly, there was an overlap of activation and incomplete inactivation at potentials from -60 to -40 mV, suggesting a "window" current that was responsible for subthreshold variations of membrane potential and might underlie conditioning-specific increases in Purkinje cell excitability. The potassium current was inhibited by 4-AP and by Heteropodatoxin, a specific blocker of Kv4.2 and Kv4.3 channels, but not by Stromatoxin, a blocker of Kv4.2 channels. Mouse monoclonal antibody labeling identified both Kv4.3 and Kv4.2 subunits in the granule cell layer but only Kv4.3 subunits in the molecular layer. This is the first demonstration of A-type currents in adult, rabbit Purkinje cells that may play a role in regulating membrane potential and firing frequency and comprise the target channel mediating conditioning-specific changes of excitability in rabbit Purkinje cell dendrites.

Animals↗

PubMed2006

Effects of 4-aminopyridine on classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response.

A large body of data suggests that potassium channels may play an important role in learning and memory. Previous in-vitro research in a number of species including Hermissenda and the rabbit suggests that a 4-aminopyridine-sensitive transient potassium channel may be involved in classical conditioning. We investigated the effects of in-vivo 4-aminopyridine administration (0.5 mg/kg) on classical conditioning of the rabbit nictitating membrane response using a battery of tests designed to assess the associative, sensory, and motor contributors of 4-aminopyridine to responding. 4-Aminopyridine enhanced both classical conditioning and conditioning-specific reflex modification compared with a saline vehicle control, and these effects had several nonassociative components including an increase in the frequency of responding to both the conditioned and the unconditioned stimuli, suggesting a sensitizing effect of the drug. Although 4-aminopyridine can have peripheral effects, it may also modify cerebellar excitability or hippocampal neurotransmitter balance resulting in heightened responsiveness to stimulation.

4-Aminopyridine↗

PubMed2006

Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response is sensitive to context.

Conditioning-specific reflex modification occurs when an unconditioned response is modified in the absence of the conditioned stimulus as a result of pairings of the conditioned stimulus and an unconditioned stimulus. In two experiments, we assessed conditioning-specific reflex modification in either a novel context (Experiment 1) or a context different from, but equally familiar in relation to, the training context (Experiment 2). Conditioning-specific reflex modification did not demonstrate sensitivity to a novel context but did demonstrate sensitivity to a change in familiar context. The data cannot be explained by unconditioned stimulus preexposure, overtraining, or context insensitivity. The results suggest that conditioning-specific reflex modification models normal stress and may be used to evaluate theories of and treatments for posttraumatic stress disorder.

Animals↗

PubMed2005

Heart rate changes during conditioning-specific reflex modification of the rabbit's (Oryctolagus cuniculus) nictitating membrane response.

Conditioning-specific reflex modification (CRM) of the rabbit's nictitating membrane response (NMR) involves changes in responding to an unconditioned stimulus (US) when the US is tested in the absence of the conditioned stimulus. Previous experiments have shown that CRM is a function of the type and intensity of the aversive US used during classical conditioning. As a result, it has been suggested that CRM may be mediated, at least in part, by the aversiveness of the US. Here, we show that by using a moderately intense electrical pulse to the skin as a US, CRM of the rabbit NMR is accompanied by an increase in heart rate. The largest changes in heart rate occur at US intensities that produce the strongest levels of CRM. The heart rate data show that there may be an increased emotional/arousal component to the US that is correlated with CRM and support the use of CRM as a potential model for posttraumatic stress disorder.

Adaptation, Physiological↗

PubMed2005

Conditioning-specific reflex modification of rabbit (Oryctolagus cuniculus) heart rate.

Conditioning-specific reflex modification (CRM) describes changes in rabbit (Oryctolagus cuniculus) nictitating membrane responses (NMR) to an unconditioned stimulus (US) when the US is tested by itself after pairings of tone and electrodermal stimulation. Although CRM has been replicated, it is unclear whether it occurs in response systems other than that of the NMR. The authors report that CRM of rabbit heart rate (HR) can occur following HR conditioning. A US that elicits HR acceleration before conditioning can elicit HR deceleration after conditioning. The rabbits' electrocardiograms showed both HR conditioning and HR CRM were correlated with an increased PQ interval--an index of parasympathetic function mediated by the vagus. The data suggest conditioned HR deceleration can generalize from conditioned stimulus to US as a function of conditioning.

Animals↗

PubMed2003

Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease.

Despite the crucial role played by cholesterol and copper in nutrition and normal brain function, recent evidence indicates that they may both be important factors in the etiology of Alzheimer's disease (AD). Here we provide critical evidence for the role of cholesterol and copper in AD by showing that the addition of trace amounts of copper (0.12 ppm) to water given to cholesterol-fed rabbits can induce beta-amyloid (Abeta) accumulation, including senile plaque-like structures in the hippocampus and temporal lobe, and can significantly retard the ability of rabbits to learn a difficult trace conditioning task. The Abeta deposits do not affect the ability of rabbits to detect or respond to the training stimuli nor to learn a simpler delay conditioning task. Trace amounts of copper in drinking water may influence clearance of Abeta from the brain at the level of the interface between the blood and cerebrovasculature and combined with high cholesterol may be a key component to the accumulation of Abeta in the brain, having a significant impact on learning and memory. Cholesterol-fed rabbits have at least 12 pathological markers seen in AD, suggesting that the cholesterol-fed rabbit is a good animal model for studying AD.

Alzheimer Disease↗

PubMed2003

Single-cue delay and trace classical conditioning in schizophrenia.

BACKGROUND: Classical conditioning provides a means of addressing mechanisms of learning and can therefore help understand the pathophysiology of memory alteration in schizophrenia. METHODS: Single cue delay and trace eyeblink conditioning were used in patients with schizophrenia and matched normal control subjects to explore, respectively, cerebellar and hippocampal integrity during learning. We measured percent of conditioned (CRs) and unconditioned responses (URs), their amplitude, and onset and peak latencies. We also accounted for spontaneous blink rates and stimulus-induced responses before learning. RESULTS: During delay conditioning, patients showed CRs with longer onset and peak latencies and improved efficiency compared to normal volunteers without there being differences between patients and normal control subjects in the percentage of CRs. During trace conditioning, neither group showed an increase in CRs as a function of conditioned stimulus-unconditioned stimulus pairings, in part because the level of spontaneous blink rates exceeded the level of CRs; however, patients with schizophrenia showed increased responding 150-400 msec after the conditioned stimulus and in the last 100-150 msec before the unconditioned stimulus, whereas normal control subjects showed only the latter type of responses. The former type of response was more frequent in patients with schizophrenia even before either trace or delay conditioning. CONCLUSIONS: These results suggest integrity of cerebellar mechanisms underlying conditioning, although the altered timing of CRs in patients may indicate differences in the modulation of such responses. Both the greater CR onset latency during delay and the presence of early nonadaptive responses during trace are compatible with the pattern of responding seen in animals with hippocampal damage.

Blinking↗

PubMed2003

Cholesterol modifies classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response.

Cholesterol plays an important role in synapse formation, receptor function, and synaptic plasticity, and animal studies show that modifying cholesterol may improve learning and memory. Other data show that feeding animals cholesterol can induce beta amyloid accumulation. Rabbits (Oryctolagus cuniculus) fed 2% cholesterol for 8 weeks were given trace conditioning of the nictitating membrane response using a 100-ms tone, a 700-ms trace, and periorbital electrical stimulation or airpuff. Rabbits fed cholesterol showed significant facilitation of trace conditioning to airpuff and conditioning-specific reflex modification to periorbital electrical stimulation and airpuff. The cholesterol-fed rabbits had beta amyloid accumulation in the cortex, but little in the hippocampus. The data suggest cholesterol had facilitative effects that outweighed potential amnesic effects of cortical beta amyloid.

Amyloid beta-Peptides↗

PubMed2003

Classical conditioning and modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response.

A fundamental tenet of behavior is that a reflex is automatic, unconscious, involuntary, and relatively invariant. However, we have discovered that a reflex can change dramatically as a function of classical conditioning, and this change can be demonstrated independently of the conditioned stimulus. We have termed this phenomenon conditioning-specific reflex modification (CRM). Although the behavioral laws and neural substrates of nonassociative reflex changes have been identified, the behavioral laws and neural substrates of CRM are only now being revealed. For example, CRM is similar to classical conditioning in that (a) it is a function of both the strength of conditioning and (b) the strength of the unconditioned stimulus, (c) it can be extinguished, and (d) it can be generalized from one unconditioned stimulus to another. Preliminary analysis suggests that CRM may have some features in common with post-traumatic stress disorder and may provide insights into treatment of the disorder.

Animals↗

PubMed2003

Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response: US intensity effects.

Conditioning-specific reflex modification (CRM) of the rabbit's nictitating membrane response (NMR) describes changes in responding to an unconditioned stimulus (US) when the rabbit is tested in the absence of the conditioned stimulus. Specifically, after at least 3 days of tone-electrical stimulation pairings, responses to the US increase in size, especially at intensities weaker than the training intensity. CRM is similar to classical conditioning in that it is a function of the strength of conditioning, it can be extinguished, and it can be generalized from one stimulus to another. To compare CRM and classical conditioning further, we conducted three experiments to examine the effects of US intensity (1.0, 2.0, and 4.0 mA) on CRM. CRM was weak following conditioning with 1.0 mA and extremely strong following conditioning with 2.0 mA and 4.0 mA. The data suggest that CRM is a function of US intensity and have implications for posttraumatic stress disorder, a disorder potentially modeled by CRM.

Animals↗