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C R Gallistel

Publications and source records attributed to C R Gallistel.

At least 37 records · Page 2Linked to original sources

Saturation of subjective reward magnitude as a function of current and pulse frequency.

In rats with electrodes in the medial forebrain bundle, the upper portion of the function relating the experienced magnitude of the reward to pulse frequency was determined at currents ranging from 100 to 1,000 microA. The pulse frequency required to produce an asymptotic level of reward was inversely proportional to current except at the lowest currents and highest pulse frequencies. At a given current, the subjective reward magnitude functions decelerated to an asymptote over an interval in which the pulse frequency doubled or tripled. The asymptotic level of reward was approximately constant for currents between 200 and 1,000 microA but declined substantially at currents at or below 100 microA and pulse frequencies at or above 250 to 400 pulses per second. The results are consistent with the hypothesis that the magnitude of the experienced reward depends only on the number of action potentials generated by the train of pulses in the bundle of reward-relevant axons.

Animals↗

Kinetics of matching.

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

Animals↗

Subjective reward magnitude of medial forebrain stimulation as a function of train duration and pulse frequency.

The growth of the subjective reward magnitude of medial forebrain bundle stimulation in the rat (Sprague-Dawley) as a function of train duration and pulse frequency was measured in 2 ways: (a) a titration method, which used differences in rate of reward on 2 levers to compensate for differences in the magnitude of the rewards; and (b) a direct method, in which the ratio of the reward magnitudes at the 2 levers was assumed to be given by the ratio of times spent on each lever. The results of the 2 methods agree. Reward magnitude grows as approximately a power function of train duration up to train durations of about 1 s, then declines somewhat over the interval from 2-20 s. The exponent of growth varies from 0.4 to 2.3. With stronger stimulation (higher pulse frequency), peak reward magnitude is bigger, but the saturating train duration is approximately the same.

Animals↗

The function relating the subjective magnitude of brain stimulation reward to stimulation strength varies with site of stimulation.

A two-lever choice paradigm with concurrent variable interval schedules of reward was used to measure the growth in the subjective magnitude of reward as a function of current, by finding the adjustment in the stimulating current required to offset a given difference in the rates at which two rewards were received. Increasing current by a factor of 2 increased subjective reward magnitude by a factor ranging from as little as 3 to as much as 4,000. This range was about as great between electrodes within one rat as between electrodes and rats. In the light of earlier findings regarding the equivalent effects of increments is current and pulse frequency, these large differences cannot readily be explained by differing fiber densities at the site of stimulation. It is suggested that the medial forebrain bundle terminates in more than one spatio-temporal integration mechanism. The magnitude of the spatio-temporally integrated effect of a barrage of action potentials in the reward-relevant axons depends on which subset of reward-relevant axons is excited by the stimulation.

Action Potentials↗

Preverbal and verbal counting and computation.

We describe the preverbal system of counting and arithmetic reasoning revealed by experiments on numerical representations in animals. In this system, numerosities are represented by magnitudes, which are rapidly but inaccurately generated by the Meck and Church (1983) preverbal counting mechanism. We suggest the following. (1) The preverbal counting mechanism is the source of the implicit principles that guide the acquisition of verbal counting. (2) The preverbal system of arithmetic computation provides the framework for the assimilation of the verbal system. (3) Learning to count involves, in part, learning a mapping from the preverbal numerical magnitudes to the verbal and written number symbols and the inverse mappings from these symbols to the preverbal magnitudes. (4) Subitizing is the use of the preverbal counting process and the mapping from the resulting magnitudes to number words in order to generate rapidly the number words for small numerosities. (5) The retrieval of the number facts, which plays a central role in verbal computation, is mediated via the inverse mappings from verbal and written numbers to the preverbal magnitudes and the use of these magnitudes to find the appropriate cells in tabular arrangements of the answers. (6) This model of the fact retrieval process accounts for the salient features of the reaction time differences and error patterns revealed by experiments on mental arithmetic. (7) The application of verbal and written computational algorithms goes on in parallel with, and is to some extent guided by, preverbal computations, both in the child and in the adult.

Animals↗

Characteristics of spatiotemporal integration in the priming and rewarding effects of medial forebrain bundle stimulation.

Only the function relating the required pulse frequency to the interburst interval discriminates between the priming effect and the rewarding effect: Separating two short bursts of pulses has no effect on their combined rewarding effect, but it enhances their priming effect. There are significant nonscalar differences between animals in the number-current and charge-duration functions for priming and reward, but there are no significant differences in these functions between effects within animals. Substantially more electrical-stimulation is required to produce good priming than to produce a reward that sustains maximum possible levels of performance. These findings suggest that the priming effect is a transient excitement generated by the receipt of one or more very large rewards. The discussion elaborates a model that reconciles this hypothesis with the earlier finding that the rewarding effect may be blocked pharmacologically without blocking priming.

Animals↗

Effect of current on the maximum possible reward.

Using a 2-lever choice paradigm with concurrent variable interval schedules of reward, it was found that when pulse frequency is increased, the preference-determining rewarding effect of 0.5-s trains of brief cathodal pulses delivered to the medial forebrain bundle of the rat saturates (stops increasing) at values ranging from 200 to 631 pulses/s (pps). Raising the current lowered the saturation frequency, which confirms earlier, more extensive findings showing that the rewarding effect of short trains saturates at pulse frequencies that vary from less than 100 pps to more than 800 pps, depending on the current. It was also found that the maximum possible reward--the magnitude of the reward at or beyond the saturation pulse frequency--increases with increasing current. Thus, increasing the current reduces the saturation frequency but increases the subjective magnitude of the maximum possible reward.

Animals↗

Measuring the subjective magnitude of brain stimulation reward by titration with rate of reward.

The magnitude of experienced reward as a function of the pulse frequency and current in trains of fixed duration delivered to the medial forebrain bundle of the rat was measured using a new psychophysical method in which the parameters of the brain stimulation reward on one lever are adjusted to offset the effect of changing the rate of reward on a competing lever. Subjective reward magnitude is a steep sigmoidal function of both pulse frequency and current. The growth of reward to its half-maximal level was approximated by a power function with an exponent that varied from 2 to 10. Within a subject, the exponent was the same for both current and pulse frequency, which supports the hypothesis that the magnitude of reward from a train of fixed duration is determined by the rate at which action potentials are generated in the population of reward-relevant axons (the counter hypothesis). This rate is proportional to Current x Pulse Frequency.

Animals↗

The analytic and functional accuracy of a video densitometry system.

Applications using radiotracers and quantitative film autoradiography are increasing dramatically in the neurosciences. Microcomputer-based image analyzing systems with video input have been developed to provide rapid quantification of autoradiographic images on relatively inexpensive systems. However, there has been some question as to whether such systems can reliably produce high levels of densitometric accuracy, especially when compared to mechanical scanners which are standard in research requiring extreme fidelity of measurement. We report methods and results from tests done to determine the analytical and functional accuracy of the Drexel Unix-based Microcomputer image Analysis System (DUMAS), which is a video densitometric system designed to provide quantitative data from autoradiograms. Analytical accuracy was determined by measuring photometric uniformity, the optical density transfer function, temporal stability, geometric uniformity, and flare. In addition, data are provided on the resolution of the system at several magnifications. Functional accuracy, the accuracy of the estimates of mean isotope concentrations in diverse neural structures, was determined by comparing the results obtained on the DUMAS system with the results from analyzing the same [14C]2-deoxyglucose images with two different Optronics P1000 systems. Our results show that, provided care is taken in the choice of a camera and a light source, the analytic accuracy of videodensitometry is high. Its functional accuracy is also high in that measurements of radioisotope concentrations in diverse neural structures made on the DUMAS system agree closely with the measurements from a properly adjusted Optronics P1000 system. The rapidity and economy of videodensitometry is not, therefore, obtained at the sacrifice of densitometric accuracy. Given adequately tested hardware and provided that suitable checks on instrument calibration and adjustment are made, the errors in autoradiographic quantification due to the image analyzing system itself are minor in comparison to other sources of error, including, as we show, variations in the user's delineation of the boundaries of neural structures.

Autoradiography↗

Reward saturation in medial forebrain bundle self-stimulation.

A rate-frequency curve in self-stimulation experiments plots the response rate as a function of the frequency of stimulation pulses, yielding a steeply rising, roughly sigmoidal curve. Altering stimulation reward efficacy results in lateral shifts of this curve, while altering the operant performance capacity of the rat results in primarily vertical shifts. One hypothesis explaining the lateral stability of the curve in the face of performance-altering manipulations is that the stimulation reward effect saturates at the frequency where the curve asymptotes. In the first experiment we determined the frequency of rate-frequency curve asymptote in two paradigms, runway and lever-pressing, and compared it to the reward saturation frequency determined in a discrete choice procedure. Results indicate that reward often saturates at frequencies above the rate-frequency asymptote point, which does not support the above hypothesis; levelling-off of the rate-frequency function is most likely a result of performance ceiling factors. In a second experiment, increases in stimulation current reduced the saturation frequency, indicating that saturation is not determined by an upper limit on the signal carrying capacity of the directly excited axons.

Action Potentials↗

Quantitative determination of the effects of catecholaminergic agonists and antagonists on the rewarding efficacy of brain stimulation.

The effects of amphetamine, clonidine, molindone, pimozide and yohimbine on the rewarding efficacy of electrical stimulation of the medial forebrain bundle in the rat were determined from the effects of these drugs on the rate-frequency function, which is the plot of the rat's rate of pressing a lever against the frequency of the pulses in a rewarding train of fixed duration. These catecholaminergic agonists and antagonists produced dose-dependent alterations in the measurable rewarding efficacy, but only up to a factor of about 2, even though the method is capable of measuring 25-30-fold changes. At elevated doses, the effects on rewarding efficacy became unmeasurable, because the animals would not consistently self-stimulate at any parameters of stimulation. Amphetamine (0.5-3 mg/kg) enhanced rewarding efficacy. Clonidine (0.05-0.4 mg/kg), molindone (0.25-1 mg/kg) and pimozide (0.1-0.6 mg/kg) attenuated it. Pimozide and clonidine were equipotent despite their radically different receptor affinities. The effects of pimozide, clonidine and amphetamine were approximately additive (amphetamine cancelled the effects of pimozide and clonidine, while clonidine augmented the effect of pimozide). The alpha 2 antagonist yohimbine (0.05-10 mg/kg) had the same effect as the alpha 2 agonist clonidine (attenuation of rewarding efficacy), but these effects did not combine additively: yohimbine neither cancelled nor augmented the effect of clonidine. It is suggested that catecholaminergic agonists and antagonists do not alter the magnitude of the rewarding signal by acting on postsynaptic receptors in the reward pathway; rather, they may drive beyond functional limits a variable that is crucial to the proper recording of the magnitude of the rewarding signal.

Amphetamine↗

The role of the dopaminergic projections in MFB self-stimulation.

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

Amphetamine↗

The role of the dopaminergic projections in MFB self-stimulation.

Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect.

Amphetamine↗

Does the perception of reward magnitude of self-administered electrical brain stimulation have a circadian rhythm?

The locus of rise of the rate-frequency function was determined for rats at many times of day to ascertain whether the circadian fluctuations in the frequency of bar pressing for electrical stimulation of the medial forebrain bundle could be accounted for by alterations in the perceived magnitude of the reward. No evidence of circadian changes in the value of the locus of rise were detectable. These findings suggest that for self-stimulation, the endogenous circadian rhythm generating apparatus affects behavior through neural mechanisms similar to those through which motivational and arousal variables act. The animal's requirement for verity of memorial representations may underlie the lack of a circadian rhythm in the locus of rise.

Animals↗

A microcomputer-based method for physiologically interpretable measurement of the rewarding efficacy of brain stimulation.

Determination of the function relating rate of pressing to the number of pulses in a train of fixed duration (the rate-frequency function) yields a physiologically interpretable measure of changes in the rewarding efficacy of the stimulation, because the number of action potentials in the reward-relevant first stage axons is directly proportional to the number of pulses in the train. We describe a system, based on a low cost microcomputer, which permits determination of 16-data-point rate-frequency functions in 4-6 animals simultaneously in less than 10 minutes. We give an empirical and theoretical justification for using the curve-shift measurement procedure in drug and lesion work, where the experimental treatments must be presumed to have substantial effects on performance factors.

Animals↗