Loss Of Stimulus Control Research Articles

Basolateral amygdala to posterior piriform cortex connectivity ensures precision in learned odor threat

Odor perception can both evoke emotional states and be shaped by emotional or hedonic states. The amygdala complex plays an important role in recognition of, and response to, hedonically valenced stimuli, and has strong, reciprocal connectivity with the primary olfactory (piriform) cortex. Here, we used differential odor-threat conditioning in rats to test the role of basolateral amygdala (BLA) input to the piriform cortex in acquisition and expression of learned olfactory threat responses. Using local field potential recordings, we demonstrated that functional connectivity (high gamma band coherence) between the BLA and posterior piriform cortex (pPCX) is enhanced after differential threat conditioning. Optogenetic suppression of activity within the BLA prevents learned threat acquisition, as do lesions of the pPCX prior to threat conditioning (without inducing anosmia), suggesting that both regions are critical for acquisition of learned odor threat responses. However, optogenetic BLA suppression during testing did not impair threat response to the CS+ , but did induce generalization to the CS−. A similar loss of stimulus control and threat generalization was induced by selective optogenetic suppression of BLA input to pPCX. These results suggest an important role for amygdala-sensory cortical connectivity in shaping responses to threatening stimuli.

Conditioned Taste Avoidance Drug Discrimination Procedure: Assessments and Applications.

In the present chapter, we summarize much of the work on the taste avoidance drug discrimination procedure, presenting the logic for its initial introduction and the extension of the procedure in the investigation of the discriminative properties of various drugs. Results from these assessments parallel those from more traditional operant and maze designs in classifying and characterizing the discriminative properties of drug. At the same time, this design reveals a procedure that is sensitive in such assessments by indexing these stimulus properties more rapidly and at lower doses than in the more traditional procedures (in some cases for drugs heretofore resistant in their detection). Importantly, much remains to be learned about the taste avoidance procedure in that the nature of such learning remains unknown and the specific parameters under which it can be established and generalized and its neurochemical and neuroanatomical bases are largely unexplored. The application of drug discrimination learning to human drug abuse continues to be an important consideration for this specific design (as well as that of drug discrimination procedures in general), and recent parallels between drug use and food intake in terms of its regulation by interoceptive stimuli suggests a possible role of the loss of stimulus control in drug escalation and addiction (with possible therapeutic implications via the modulation of these interoceptive cues).

Baseline training history and effects of methamphetamine on performance of pigeons on an interval-bisection task

Length of baseline training influences how methamphetamine disrupts temporal performance under a peak interval schedule. Acute methamphetamine produces overestimation of time following relatively brief training, but following extended training, methamphetamine produces more general loss of stimulus control. The current study extends the study of training length on the effects of methamphetamine to an interval-bisection procedure. Six pigeons responded under a psychophysical choice procedure in which responses to one key color were correct after presentation of four shorter sample durations and responses to another key color were correct after presentation of four longer sample durations. One group of three pigeons received briefer baseline training (45 sessions), while another group received more extended training (223 sessions) prior to methamphetamine administration. There was no evidence of overestimation of time or generalized loss of stimulus control in either group. Sensitivity (precision of timing) was higher in the group with more extensive training and was disrupted by methamphetamine.

Further study of the control of place cell firing by intra-apparatus objects.

The angular positions of hippocampal place cell firing fields are accurately controlled by the position of a single salient cue card attached to the wall of a recording cylinder; when the card is rotated, fields rotate equally. In contrast, the control exerted by 3-dimensional objects placed directly in the recording arena depends on their arrangement. When three objects lie on the vertices of an isosceles triangle near the center of the cylinder they rarely exert any control over the angular positions of firing fields. However, if the isosceles triangle is dilated so that its vertices are against the apparatus wall, the objects exert virtually ideal control over angular field position. Why do the objects gain control when they are against the cylinder wall? One possibility is that the asymmetry in the object set is more easily detected when the objects are far apart so that they provide a better polarizing cue. This hypothesis assumes that the identity of individual landmarks is not recognized by the place cell system whereas their geometric arrangement provides crucial information for controlling place field positions. If this is true, putting the 3 objects against the cylinder wall on the vertices of an equilateral triangle should cause a loss of stimulus control over the angular positions of firing fields. To the contrary, we found that the firing fields of most place cells (23/29) were accurately controlled by the equilateral object arrangement. Moreover, 5/6 of the uncontrolled cells were in a single animal. These results bolster our previous suggestion that the centrally placed objects fail to control place field positions because the computations necessary to form a stable reference frame are very difficult when the animal can go between stimuli.

Low-dose apomorphine attenuates morphine-induced enhancement of brain stimulation reward

Thresholds for brain stimulation reward (BSR) delivered to the medial forebrain bundle-lateral hypothalamus were determined by means of a rate free psychophysical method. Lower doses of apomorphine (0.5 to 0.2 mg/kg) produced modest elevations in BSR thresholds. A 0.4 mg/kg dose of apomorphine resulted in emergence of Stereotypic behaviors and the loss of stimulus control. Morphine's BSR threshold lowering effects were significantly blocked by the concurrent administration of a 0.1 mg/kg dose of apomorphine. These results support the hypothesis that presynaptic dopamine neurons are involved in the mediation of morphine's reinforcing effects and that dopamine autoreceptor agonists may be of some use in the pharmacotherapy of opiate abuse.

Benzodiazepine receptor ligands have no specific action on working memory in a delayed conditional discrimination task in rats

We investigated effects of benzodiazepine (BDZ) receptor ligands on working memory in a delayed conditional discrimination (DCD) task. The BDZ receptor full agonist midazolam (0.1-1.0mg/kg) dose-dependently impaired performance independent of delay, indicating no specific effect on working memory. The non-sedative BDZ receptor partial agonist bretazenil (0.06-0.6mg/kg), the inverse agonist beta-CCM (0.05-0.45mg/kg), the partial inverse agonist FG 7142 (0.5-5.0mg/kg), the antagonist flumazenil (1-10mg/kg), and the antagonist ZK 93 426 (1-10mg/kg) did not significantly affect performance. It is concluded that BDZ ligands do not affect working memory in a positively-motivated DCD task. Midazolam also impaired performance in the no-delay condition, suggesting loss of stimulus control, possibly through an attentional impairment.

Progressive Decline of Picture Naming in an Aging down Syndrome Man with Dementia

This study was conducted to monitor picture naming longitudinally in a 59-yr.-old Down syndrome man with diagnosed dementia. On the test, the subject was shown a series of 40 pictures, and his task was to speak their names. Correct naming responses were followed by pennies. The test was repeated periodically over the course of 20 mo. The subject initially achieved 100% correct scores and maintained accuracy until the tenth month. Thereafter, his scores declined, gradually at first and then precipitously, until the subject scored less than 30% correct on the final test. Error analysis showed that low scores generally reflected loss of stimulus control by relevant characteristics of the test pictures; control apparently shifted to irrelevant features of the task. The results suggest that naming tests may ultimately prove useful in defining and documenting the nature of deterioration in Down dementia.

Progressive Decline of Picture Naming in an Aging down Syndrome Man with Dementia

This study was conducted to monitor picture naming longitudinally in a 59-yr.-old Down syndrome man with diagnosed dementia. On the test, the subject was shown a series of 40 pictures, and his task was to speak their names. Correct naming responses were followed by pennies. The test was repeated periodically over the course of 20 mo. The subject initially achieved 100% correct scores and maintained accuracy until the tenth month. Thereafter, his scores declined, gradually at first and then precipitously, until the subject scored less than 30% correct on the final test. Error analysis showed that low scores generally reflected loss of stimulus control by relevant characteristics of the test pictures; control apparently shifted to irrelevant features of the task. The results suggest that naming tests may ultimately prove useful in defining and documenting the nature of deterioration in Down dementia.

Discrete-trial control of morphine self-injection behaviour in squirrel monkeys: effects of naloxone, morphine, and chlorpromazine

Intravenous morphine self-injection behaviour was studied using a new discrete-trials procedure in monkeys. Morphine self-injection was most probable when small unit doses (10–100 μg/kg per injection) were available and least frequent, even in comparison with saline substitution, at doses of 300 and 400 μg/kg per injection. Despite variation of the inter-trial interval from 50 to 300 s small injection doses (25 and 100 μg/kg per injection) continued to sustain more frequent self-injection responding than a larger unit dose (400 μg/kg per injection). When daily sessions consisted of 40 trials at an inter-trial interval of 50 s, morphine self-injection behaviour (100 μg/kg per injection) was neither increased nor consistently decreased by naloxone pretreatment (0.1–1.0 mg/kg im). In subsequent experiments, daily sessions consisted of two sets of 40 discrete trials, separated by a time-out (TO) period. When monkeys were pretreated with morphine (5.6 mg/kg im) before a given session, responding for drug injections was suppressed; the effect was reversed by naloxone (1 mg/kg im) which, if injected at TO, reinstated morphine self-administration behaviour. When an injection of chlorpromazine (5.6 mg/kg im) preceded a given session, responding for morphine injections was also suppressed; naloxone (1 mg/kg im) failed to reinstate chlorpromazine-suppressed responding, indicating that naloxone acted as an acute morphine antagonist under some circumstances, but did not otherwise influence behaviour. When the unit dose of morphine was increased to 200 μg/kg per injection, naloxone (1–3 mg/kg im) elicited agitation and occasional vomiting in each monkey tested, but did not suppress their drug-taking behaviour. Though small increases in morphine intake were observed after naloxone pretreatment, substantial increases in response output during the inter-trial interval, with a consequent loss of stimulus control normally exerted by the trial signal, were observed. These results were interpreted in terms of acute, antagonist-precipitated withdrawal signs, not evident in response to naloxone pretreatment when drug self-injection responding was maintained on a daily basis by a limited number of smaller unit injection doses of morphine (50 or 100 μg/kg per injection).

Animal psychophysics: improvements in the tracking method.

It is difficult to maintain stimulus control in animal psychophysical studies using the tracking method. Loss of stimulus control is characterized by wandering thresholds and responses in the absence of the stimulus. Rats were trained to make a variable number of licking responses to turn on an auditory stimulus. A response on a lever in the presence of the stimulus was reinforced with food. Two precedures were added to improve stimulus control. First, lever responses in the absence of the stimulus raised the intensity of the stimulus at the next presentation; second, rate of reinforcement in the threshold region was maintained at about the same level as that in the suprathreshold region by reducing the number of licking responses required to turn on the stimulus. Using these two procedures, stimulus control was improved and maintained and reliable auditory intensity thresholds were obtained.