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PubMed1998

Slow stochastic Hebbian learning of classes of stimuli in a recurrent neural network.

We study unsupervised Hebbian learning in a recurrent network in which synapses have a finite number of stable states. Stimuli received by the network are drawn at random at each presentation from a set of classes. Each class is defined as a cluster in stimulus space, centred on the class prototype. The presentation protocol is chosen to mimic the protocols of visual memory experiments in which a set of stimuli is presented repeatedly in a random way. The statistics of the input stream may be stationary, or changing. Each stimulus induces, in a stochastic way, transitions between stable synaptic states. Learning dynamics is studied analytically in the slow learning limit, in which a given stimulus has to be presented many times before it is memorized, i.e. before synaptic modifications enable a pattern of activity correlated with the stimulus to become an attractor of the recurrent network. We show that in this limit the synaptic matrix becomes more correlated with the class prototypes than with any of the instances of the class. We also show that the number of classes that can be learned increases sharply when the coding level decreases, and determine the speeds of learning and forgetting of classes in the case of changes in the statistics of the input stream.

Generalization, Stimulus↗
PubMed2006

When motion appears stopped: stereo motion standstill.

Motion standstill is different from the usual perceptual experiences associated with objects in motion. In motion standstill, a pattern that is moving quite rapidly is perceived as being motionless, and yet its details are not blurred but clearly visible. We revisited motion standstill in dynamic random-dot stereograms similar to those first used by Julesz and Payne [Julesz B, Payne R (1968) Vision Res 8:433-444]. Three improvements were made to their paradigm to avoid possible confounds: The temporal frequency of the motion stimuli was manipulated independently from that of individual stereo gratings so that the failure of motion perception is not due to inability to compute stereo. The motion of the stereo gratings was continuous across the visual field so that the perceived pattern in motion standstill was not a simple average of a back-and-forth display wobble over time. Observers discriminated three spatial frequencies to demonstrate pattern recognition. Three objective psychophysical methods, instead of merely self-report, were used to objectively demonstrate motion standstill. Our results confirm that motion standstill occurs in dynamic random-dot stereogram motion displays at 4-6 Hz. Motion standstill occurs when the stimulus spatiotemporal frequency combination exceeds that of the salience-based third-order motion system in a spatiotemporal frequency range in which the shape and depth systems still function. The ability of shape systems to extract a representative image from a series of moving samples is a significant component of a biological system's ability to derive a stable perceptual world from a constantly changing visual environment.

Adult↗
PubMed1971

Stimulus control during conditional discrimination.

Pigeons were used to assess stimulus control during the development of a conditional discrimination. The training consisted of three stages. In Stage 1, key pecks were reinforced in the presence of a white line tilted 40 degrees to the right of vertical on a green background and non-reinforced when the same line appeared on a red background. In Stage 2, key pecks were reinforced when a white vertical line appeared on a red background and were non-reinforced in the presence of a 40 degrees slanted line on a red background. In Stage 3, key pecks were reinforced in the presence of the green background regardless of the line tilt, but were differentially reinforced in the presence of the red background (as in Stage 2). Generalization tests were conducted after each stage of training and consisted of five white lines on backgrounds that were green, red, or dark. The effects of the differential reinforcement contingencies on control by line orientation were restricted to the condition in which the red light appeared and resulted in behavioral control that could be characterized as: if red, pay closer attention to line tilt than if not red.

Animals↗
PubMed1988

Phencyclidine-like discriminative stimulus effects of the stereoisomers of alpha- and beta-cyclazocine in rats.

Stereoisomers of alpha- and beta-cyclazocine were tested in rats trained to discriminate phencyclidine (PCP; 3.0 mg/kg i.p.) from saline in a two-lever, food-reinforced, drug-discrimination procedure. (+)-Alpha-cyclazocine and both (+)- and (-)-beta-cyclazocine substituted for PCP. Neither (+/-) nor (-)-alpha-cyclazocine substituted for PCP, although both compounds had potent, response-rate decreasing effects. When these two drugs were tested in combination with naltrexone, rate-suppressing effects were somewhat attenuated and both then resulted in substantial PCP-lever responding. Thus, PCP-like effects in the alpha series can be masked by opiate effects. (-)-Beta-cyclazocine was the most potent compound for mimicking the PCP discriminative stimulus, being 4 to 5 times more potent than PCP itself. The (+)-isomers in both the alpha and beta series were equipotent and over 10 times less potent than PCP. Thus, both stereoisomers of beta-cyclazocine have PCP-like discriminative stimulus properties and the (-)-isomer, in particular, is a very potent, selective, PCP-like compound. The stereoisomers of beta-cyclazocine have over a 50-fold potency difference for PCP-like effects, evidencing greater stereoselectivity for these actions than is commonly obtained with 6,7-benzomorphans. The stereoisomers of beta-cyclazocine should prove to be useful tools for studying the PCP/sigma-like effects of opioids.

Animals↗
PubMed1993

Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects.

Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 micrograms) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats.

The discriminative stimulus effects of direct and indirect-acting GABAergic drugs were investigated in rats trained to discriminate 5 mg/kg pentobarbital (PB) from saline under a two-lever fixed ratio (FR) 32 schedule of food reinforcement. PB and diazepam produced dose-dependent substitution for the training dose of PB with response rate reduction only at doses above those producing full substitution. Muscimol, thiomuscimol and 4,5,6,7-tetrahydroisoxazolo [5,4-c]-pyridin-3-ol (THIP) produced intermediate levels of pentobarbital-lever responding (40-60%), accompanied by dose-dependent decreases in rates of responding following THIP and muscimol administration. The GABAA agonist progabide and its metabolite 4-([(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)methylene]amino)] butyric acid (SL 75102) also partially substituted for PB, producing means of 39-73% PB-lever responding. The GABAB agonist, baclofen, completely failed to substitute for PB even at doses that decreased rates of responding. These results show that the discriminative stimulus effects of indirect GABAA agonists, PB and diazepam, although similar to one another, differ from those of direct GABAA receptor agonists, which produced only partial substitution for PB. The GABAB agonist, baclofen, can be distinguished by lacking any ability to substitute for PB. These results contribute to a further understanding of the similarities and differences in the behavioral effects of different types of GABA agonists.

Animals↗
PubMed2002

Stimulus control by same-versus-different relations among multiple visual stimuli.

The authors devised a go/no-go discrimination learning task that allowed but did not require pigeons to report (a) from which of 2 different sets a collection of visual items was drawn and (b) the relations between or among the items as being the same as or different from one another. The results of 2 experiments using this task disclosed stimulus control by the particular items in the arrays and by the same-different relations exemplified by those items. Relational and item control depended on how many items were in the arrays. Same-different discrimination was evident with 2-item displays, but it was much stronger with 6 or more items. These findings help to define the substrates of advanced conceptual behavior.

Analysis of Variance↗
PubMed1973

The unilateral engram.

It is proposed that the corpus callosum has a major role in the processes of memory; first, by providing access by each hemisphere to memory traces stored in the other, and second, by controlling the formation of memory traces in such a way that they are laid down in only one hemisphere instead of in both. This dual mechanism would have the effect of doubling the mnemonic storage capacity of the brain. Evidence in favor of this hypothesis in briefly reviewed. It is also supported by experiments using electrical excitation of the striate cortex as a conditional stimulus in macaques, and by experiments on maze behavior in the m e species. Experiments with the anterior commissure, on the other hand, show that it, in contrast to the splenium of the corpus callosum, can actually transfer an engram from one hemisphere to the other. Finally, it is shown that the splenium provides an effective path of communication between the central visual system in one hemisphere and the amygdala in the other.

Amygdala↗
PubMed1994

Drug discrimination using a Pavlovian conditional discrimination paradigm in pigeons.

Three pigeons were studied using a discriminated autoshaping procedure in which the presence or absence of methadone served as a conditional stimulus signalling which of two key light CSs would be followed by grain access. Drug sessions alternated randomly with no-drug sessions. Methadone (2.0 mg/kg) was administered prior to drug sessions in which a black vertical line on a white background served as CS+ and a diffuse white keylight served as CS- (reversed for bird 681). Saline or no injection was administered prior to no-drug sessions and the CS+/CS- contingencies were reversed. Discriminated performances emerged in which over 80% of the responding occurred to the appropriate stimulus. Stimulus control by methadone was assessed by presenting a range of methadone doses during 10-trial extinction sessions. A graded dose-effect curve was produced with low doses of methadone controlling saline-appropriate responding and higher doses controlling drug-appropriate responding. A range of doses of morphine, cocaine, and pentobarbital were also tested. Morphine produced methadone-appropriate responding while cocaine and pentobarbital did not.

Animals↗
PubMed1994

Discriminative stimulus effects of dextromethorphan in the rat.

This study was performed to characterize pharmacologically the discriminative stimulus effects of dextromethorphan, an antitussive that binds with high affinity to a subtype of sigma site in the brain. Dextrorphan, a metabolite of dextromethorphan, has phencyclidine (PCP)-like effects. Therefore, training was conducted with dextromethorphan injected by the SC route, which minimizes dextrorphan formation compared to the IP route. The training dose used, 30 mg/kg, by the SC route did not occasion selection of the PCP-appropriate choice lever in rats discriminating IP injections of 2.0 mg/kg PCP from saline. (In contrast, by the IP route the ED50 of dextromethorphan for PCP-appropriate lever selection was 21.7 mg/kg). In rats discriminating 30 mg/kg (SC) of dextromethorphan from distilled water, dextromethorphan was slightly more potent SC than it was IP (ED50s for dextromethorphan-appropriate lever selection: 8.5 and 14.9 mg/kg, respectively). These animals generalized dose-dependently and completely to PCP and to other PCP-receptor ligands, but selected the vehicle-appropriate choice lever when tested with sigma-site ligands, mu-opioid agonists, and naltrexone. Concurrent administration of naltrexone or sigma-site ligands with 30 mg/kg dextromethorphan did not block dextromethorphan-appropriate responding. These results show that the discriminative effects of SC dextromethorphan are PCP-like and are not mediated by the high-affinity dextromethorphan binding site or by the mu-opioid receptor. Because little dextrorphan is formed when dextromethorphan is given SC and because dextromethorphan itself has low affinity for the PCP receptor, the discriminative effects of SC dextromethorphan probably are mediated by a recognition site related closely to but different from the PCP receptor.

Animals↗
PubMed1991

Color appearance in the peripheral retina: effects of stimulus size.

Hue and saturation scaling were used to measure the appearance of spectral lights as a function of stimulus size for nine loci across the horizontal retinal meridian. At a given locus, each hue (R, Y, G, and B) grew as a function of stimulus size up to some asymptotic value. The parameter values of Michaelis-Menten growth functions fitted to the hue data were used to derive the sizes of the so-called perceptive fields of the hue mechanisms. The fields for all mechanisms increased with eccentricity, and this increase was greater on the temporal than on the nasal retina. By increasing stimulus size it was possible to achieve fovealike color vision to eccentricities of 20 deg. However, even the largest stimuli failed to produce fully saturated hues at 40 deg. The retinal size scales of the four hue mechanisms were not the same; those for R and B were similar, and these mechanisms had the smallest perceptive fields everywhere. The perceptive fields of the hue mechanisms at all loci were larger than anatomical estimates of the sizes of retinal receptive fields.

Adolescent↗
PubMed1979

Morphine as a discriminative stimulus: role of periaqueductal gray neurons.

The present study investigated the degree of involvement of the periaqueductal gray (PAG) in the mediation of the discriminative stimulus (DS) effects of morphine sulfate (MS). Eleven rats were trained to discriminate MS (3 mg/kg; s.c.) from saline (1 ml/kg; s.c.) using a two-bar operant procedure. After the rats learned the discrimination to the criterion of 80% correct responding, cannulae were unilaterally implanted into the PAG. Intracerebral (i.c.) injection of MS (1 microliter) into the PAG produced stimulus control similar to that observed following systemic MS. Doses of 0.5, 1.0, 2.0 and 4.0 microgram elicited MS-correct responding of 27, 57, 63 and 77% respectively. The highest intraPAG MS dose elicited significantly more MS correct responding than did either systemic or the i.c. injection of saline, while not differing from systemically-administered MS. These results suggest that the PAG may at least be partially responsible for the generation of morphine's DS effect when administered s.c.

Animals↗
PubMed1994

Similarity and discrimination: a selective review and a connectionist model.

The 1st part of this article evaluates the extent to which 2 elemental theories of conditioning, stimulus sampling theory and the Rescorla-Wagner (1972) theory, are able to account for the influence of similarity on discrimination learning. A number of findings are reviewed that are inconsistent with predictions derived from these theories, either in their present form or in various modified forms. The 2nd part of the article is concerned with developing an alternative, configural account for discrimination learning. In contrast to previous configural theories, the present version is set within the framework of a connectionist network.

Animals↗
PubMed1988

Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-D-aspartate receptors?

Rats were trained to discriminate phencyclidine (PCP) from saline at doses of 2 and 4 mg/kg, using a two-lever food reinforced operant technique. +/- N-allylnormetazocine (+/- SKF 10047), +5-methyl-10,11-dihydro-5H-dibenzo[A,D]cyclohepten-5,10-imine MK 801), 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) and ifenprodil, which have been shown to antagonise the effects of N-methyl-D-aspartate (NMDA), were tested for their ability to give rise to PCP-appropriate responding. In rats trained at both doses of PCP, +/- SKF 10047 (2-12 mg/kg) and MK 801 (0.0125-0.2 mg/kg) produced dose-related responding on the lever associated with PCP injection. The relative potency of these two compounds was the same in the two groups of animals, but their absolute potencies to produce a PCP-like discriminative stimulus were dependent on the training dose of PCP. In contrast, neither the competitive NMDA antagonist CPP (4-20 mg/kg) nor the non-competitive antagonist ifenprodil (2-12 mg/kg) produced PCP-appropriate responding and ifenprodil (4 mg/kg) neither potentiated nor antagonised PCP. These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA-subtype of glutamate receptors.

Adrenergic beta-Antagonists↗
PubMed1998

The effects of beta-carbolines in rats trained with ibogaine as a discriminative stimulus.

The structural features and hallucinogenic properties shared by ibogaine and certain beta-carbolines prompted the evaluation of several representative beta-carbolines in rats trained with ibogaine as a discriminative stimulus. In a previous report from our laboratory harmaline completely substituted for ibogaine (83.5%). In the present study, only 6-methoxyharmalan completely substituted (86.3%). However, partial substitution was observed with harmine, harmane, harmalol, and tetrahydro-beta-carboline (THBC). Norharmane and 6,7-dimethoxy-4-ethyl-carboline-3-carboxylate (DMCM) failed to produce appreciable substitution. These results provide evidence for an ibogaine-like ether this extends to the previously reported anti-addictive effects of ibogaine remains to be established.

Animals↗
PubMed1994

A three-choice haloperidol-saline-cocaine drug discrimination task in rats.

This study was conducted to test whether rats could be trained and successfully maintain a three-choice drug discrimination task using 0.1 mg/kg haloperidol (SC, 2-h pretreatment), saline (IP or SC, 2 h and 15 min pretreatment), and 10 mg/kg cocaine (IP, 15-min pretreatment) as training stimuli. Six male Sprague-Dawley rats achieved criterion performance for stimulus control by these training stimuli under a fixed-ratio-5 schedule of food reinforced lever-press responding in an average of 164 training sessions. Dose-response functions for cocaine and haloperidol demonstrated both quantitative and qualitative specificity of the training stimuli. The data also are presented along a single pharmacological continuum (agonist-antagonist) that we hypothesize to represent a parallel subjective or interoceptive stimulus continuum associated with the drug injections. Based on the previous multidimensional model of drug stimuli dimensionality (3), this specific stimulus dimension is characterized as an unidimensional bipolar continuum represented by the hypothetical states of hedonia or euphoria on one end (cocaine) and anhedonia or depression on the opponent end (haloperidol), with a neutral (saline) centroid region. We propose that this specific three-choice drug discrimination task in rats may function as an animal analog of the subjective states associated with cocaine abuse and the subsequent withdrawal or, crash, in humans (7,8,21).

Animals↗
PubMed1991

Discriminative stimulus properties of amphetamine, cathinone, and related agents.

Although the AMPH and CATH cues have been studied extensively, inconsistent findings remain that need to be investigated. It is not known to what extent, if at all, AMPH and CATH cues differ and how they differ from the cocaine cue. The extent to which D1 and D2 receptor systems are coupled in AMPH DD assays requires further investigation. The inconsistent findings in substitution studies with nisoxetine need to be addressed in parametric studies in various species. Finally, the possibility that the AMPH cue may generate false positives in screening for drug abuse potential needs to be evaluated.

Alkaloids↗
PubMed1990

The discriminative stimulus properties of (+)-HA-966, an antagonist at the glycine/N-methyl-D-aspartate receptor.

Using a two-lever operant drug discrimination paradigm, rats have been trained to discriminate between the administration of saline and R-(+)-HA-966 (R-(+)-3-amino-1-hydroxypyrrolid-2-one, 30 mg/kg i.p.) an antagonist at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex. Drug-appropriate responding was not induced in stimulus generalisation experiments when the non-competitive NMDA receptor antagonist, phencyclidine (PCP, 1-8 mg/kg i.p.) was substituted for (+)-HA-966. Similarly, (+)-HA-966 (6-50 mg/kg i.p.) did not induce drug-appropriate responding in animals trained to discriminate PCP (3 mg/kg i.p.) from saline. The results suggest that the behavioural profile of compounds attenuating the actions of NMDA via blockade of the glycine modulatory site may be substantially different from those acting at the ion channel of the NMDA receptor complex.

Animals↗