NMDA receptor-dependent plasticity in the nucleus accumbens connects reward-predictive cues to approach responses.

Learning associations between environmental cues and rewards is a fundamental adaptive function. Via such learning, reward-predictive cues come to activate approach to locations where reward is available. The nucleus accumbens (NAc) is essential for cued approach behavior in trained subjects, and cue-evoked excitations in NAc neurons are critical for the expression of this behavior.

The role of the nucleus accumbens in learned approach behavior diminishes with training.

Nucleus accumbens dopamine plays a key role in reward-directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine-independent reward approach.

Expanding the role of striatal cholinergic interneurons and the midbrain dopamine system in appetitive instrumental conditioning.

The basal ganglia are a collection of subcortical nuclei thought to underlie a wide variety of vertebrate behavior. Although a great deal is known about the functional and physiological properties of the basal ganglia, relatively few models have been formally developed that have been tested against both behavioral and physiological data. Our previous work (Ashby FG, Crossley MJ.

Effects of varying reinforcement probability on pavlovian approach behavior and ultrasonic vocalizations in rats.

Long Evans rats (n=32) were trained for 2 weeks to respond to an auditory conditioned stimulus (CS) which signaled the delivery of a 20% sucrose unconditioned stimulus (US) with varying probabilities. Animals were randomly assigned to 1 of 4 groups. In the control groups, the CS signaled sucrose delivery with equal probabilities across two weeks, at 100% (Group 100-100) and 25% (Group 25-25) respectively.

Effects of cortical and striatal dopamine D1 receptor blockade on cued versus noncued behavioral responses.

Various lines of evidence suggest that disruptions in brain dopamine (DA) transmission produce behavioral impairments that can be overcome by salient response-eliciting environmental stimuli. We examined here whether D1 receptor blockade within striatal or frontal cortical DA target regions would differentially affect head entry responses elicited by an auditory cue compared with those occurring during noncued intertrial intervals. Rats received 2 drug-free 28-trial daily sessions in which an auditory cue was immediately followed by food delivery.

Cortical and basal ganglia contributions to habit learning and automaticity.

In the 20th century it was thought that novel behaviors are mediated primarily in cortex and that the development of automaticity is a process of transferring control to subcortical structures. However, evidence supports the view that subcortical structures, such as the striatum, make significant contributions to initial learning. More recently, there has been increasing evidence that neurons in the associative striatum are selectively activated during early learning, whereas those in the sensorimotor striatum are more active after automaticity has developed.

Dopamine D1 and D2 antagonist effects on response likelihood and duration.

Experimentally induced and parkinsonian disruptions in dopamine (DA) transmission are associated with motor abnormalities that include a reduced likelihood of behavioral response initiation and an increased duration of executed responses. Here we investigated the dopamine receptor subtypes involved in regulating these two aspects of behavior. We examined the effects of D1 family (D1/D5) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0, 0.

Stimulus-response and response-outcome learning mechanisms in the striatum.

While midbrain DA neurons show phasic activations in response to both reward-predicting and salient non-reward events, activation responses to primary and conditioned rewards are sustained for several hundreds of milliseconds beyond those elicited by salient non-reward-related stimuli. The longer-duration DA reward response and corresponding elevated DA release in striatal target sites may selectively strengthen currently-active corticostriatal synapses, i.e.

Dopaminergic mechanisms in actions and habits.

Recent studies suggest new ways to interpret dopaminergic actions in goal-directed performance and habitual responding. In the early stages of learning dopamine plays an essential role, but with extended training dopamine appears to play a decreasing role in response expression. Experimental manipulation of dopamine levels alters the correlation of cortical and striatal neural activity in behaving animals, and these dopamine-dependent changes in corticostriatal correlations may be reflected in changes in action selection in the basal ganglia.

A "good parent" function of dopamine: transient modulation of learning and performance during early stages of training.

While extracellular dopamine (DA) concentrations are increased by a wide category of salient stimuli, there is evidence to suggest that DA responses to primary and conditioned rewards may be distinct from those elicited by other types of salient events. A reward-specific mode of neuronal responding would be necessary if DA acts to strengthen behavioral response tendencies under particular environmental conditions or to set current environmental inputs as goals that direct approach responses. As described in this review, DA critically mediates both the acquisition and expression of learned behaviors during early stages of training, however, during later stages, at least some forms of learned behavior become independent of (or less dependent upon) DA transmission for their expression.

Amphetamine affects the start of responding in the peak interval timing task.

In this paper we investigate how amphetamine affects performance in a PI task by comparing two analyses of responding during peak trials. After training on 24 s fixed interval (FI-24) with 96 s peak trials, rats were given amphetamine for 4 consecutive days at doses of .5 and 1.

Dopamine receptor blockade and extinction differentially affect behavioral variability.

Dopamine (DA) neurons respond to unexpected food delivery and are inhibited during the omission of expected reward. DA receptor blockade mimics some, but not all, aspects of non-reward (extinction) conditions. It was therefore of interest to ask whether DA receptor blockade produces extinction-like increases in behavioral variability in addition to its well-known operant response-suppressing effects.

Visual search deficits in Parkinson's disease are attenuated by bottom-up target salience and top-down information.

Patients with Parkinson's disease (PD), a degenerative disorder primarily affecting the nigrostriatal dopamine system, exhibit deficits in selecting task-relevant stimuli in the presence of irrelevant stimuli, such as in visual search tasks. However, results from previous studies suggest that these deficits may vary as a function of whether selection must rely primarily on the "bottom-up" salience of the target relative to background stimuli, or whether "top-down" information about the identity of the target is available to bias selection. In the present study, moderate-to-severe medicated PD patients and age-matched controls were tested on six visual search tasks that systematically varied the relationship between bottom-up target salience (feature search, noisy feature search, conjunction search) and top-down target knowledge (Target Known versus Target Unknown).

Extended habit training reduces dopamine mediation of appetitive response expression.

A wide range of behaviors is impaired after disruption of dopamine (DA) transmission, yet behaviors that are reflexive, automatic, or elicited by salient cues often remain intact. Responses triggered by strong external cues appear to be DA independent. Here, we examined the possibility that a single behavior may become DA independent as a result of extended training.

Maintenance of response readiness in patients with Parkinson's disease: evidence from a simple reaction time task.

The authors explored the effect of Parkinson's disease (PD) on the generation and maintenance of response readiness in a simple reaction time task. They compared performance of idiopathic PD patients without dementia, age-matched controls, and younger controls over short (1-, 3-, and 6-s) and long (12- and 18-s) foreperiod intervals. After each trial, the authors probed memory for visual information that also had to be maintained during the trial interval.

Differential cingulate and caudate activation following unexpected nonrewarding stimuli.

This study examined the effects of varying the predictability of nonrewarding events on behavior and neural activation using a rapid mixed-trial functional magnetic resonance imagery (fMRI) design. Twelve adult subjects were scanned with echo planar imaging during performance of a visual detection task where the probability of events (target and nontarget) varied. This task included expected and unexpected nonrewarding events (expected target, unexpected nontarget, and omission of target) in a design that closely parallels studies of dopamine function and reward processing in the alert monkey.

Effects of dopamine antagonists on the timing of two intervals.

Rats were trained on a two-interval (12 and 36 s) temporal production task (the peak procedure). Test sessions were conducted in which either the D(1) antagonist SCH-23390 (SCH; 0.02, 0.

Opposing roles of D1 and D2 receptors in appetitive conditioning.

Previous studies have shown that D(1) receptor blockade disrupts and D(2) receptor blockade enhances long-term potentiation. These data lead to the prediction that D(1) antagonists will attenuate and D(2) antagonists will potentiate at least some types of learning. The prediction is difficult to test, however, because disruptions in either D(1) or D(2) transmission lead to reduced locomotion, exploration, and response execution and are therefore likely to impair learning that requires behavioral responding (including exploration of an environment) during the learning episode.

Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum.

Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area (VTA) respond to a wide category of salient stimuli. Activation of SN and VTA DA neurons, and consequent release of nigrostriatal and mesolimbic DA, modulates the processing of concurrent glutamate inputs to dorsal and ventral striatal target regions. According to the view described here, this occurs under conditions of unexpected environmental change regardless of whether that change is rewarding or aversive.

The role of dopamine in the timing of Pavlovian conditioned keypecking in ring doves.

The effect of dopaminergic drugs on the timing of conditioned keypecking in ring doves was studied in two experiments. Subjects were given pairings of a keylight with food and the temporal distribution of keypecks was obtained during unreinforced probe trials. Experiment 1 demonstrated that injections of pimozide before each session immediately decreased response rates but shifted timing distributions gradually to the right over several days of treatment.

Time-dependent actions of D2 family agonist quinpirole on spontaneous behavior in the rat: dissociation between sniffing and locomotion.

Rationale: Dopamine agonists elevate locomotion, sniffing, grooming, and a number of other behaviors. However, the D2 family (D2/D3/D4) agonist quinpirole, across a wide dose range, produces a period of locomotor inhibition that precedes the drug's locomotor excitatory effects.

Objectives: The present study asked whether the suppressive actions of quinpirole also extend to other aspects of spontaneous behavior, such as sniffing, rearing and grooming, or whether this suppression of locomotion occurs while the frequency of other behaviors is increased or unaffected.

Conditioned and unconditioned behavioral-cognitive effects of a dopamine antagonist in rats.

Many drugs need to be taken multiple times to achieve a therapeutic effect. Researchers have identified several mechanisms to account for the slow onset of drug action, including drug accumulation and structural changes induced by drugs. This article provides an example of a new mechanism to account for this change in drug action.

Dopamine D2 receptor blockade reduces response likelihood but does not affect latency to emit a learned sensory-motor response: implications for Parkinson's disease.

Parkinsonian behavioral deficits are reduced in the presence of strong eliciting stimuli and are most pronounced when the response requires internal generation. In the present study, rats' head entries into a food compartment were measured in the presence and absence of an eliciting stimulus. The D2 receptor blocker raclopride suppressed the emission of spontaneous head entries but did not slow head entries emitted in response to a food cue.