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UnlabelledAltered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal "no-go" pathway. To this end, we expressed the Gαi-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal-directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization.Significance statementMotivation involves a directional component that allows subjects to efficiently select the behavior that will lead to an optimal outcome and an activational component that initiates and maintains the vigor and persistence of actions. Striatal output pathways modulate motivated behavior, but it remains unknown how these pathways regulate specific components of motivation. Here, we found that the indirect pathway controls response initiation without affecting response vigor or the sensitivity to changes in the reward outcome. A specific enhancement in the activational component of motivation, however, can come at the cost of goal-directed efficiency when a sustained response is required to obtain the goal. These data should inform treatment strategies for brain disorders with impaired motivation such as schizophrenia and Parkinson's disease.

Organisms are constantly extracting information from the temporal structure of the environment, which allows them to select appropriate actions and predict impending changes.  Several lines of research have suggested that interval timing is modulated by the dopaminergic system.  It has been proposed that higher levels of dopamine cause an internal clock to speed up, whereas less dopamine causes a deceleration of the clock.  In most experiments the subjects are first trained to perform a timing task while drug free.  Consequently, most of what is known about the influence of dopaminergic modulation of timing is on well-established timing performance.  In the current study the impact of altered DA on the acquisition of temporal control was the focal question.  Thirty male Sprague-Dawley rats were distributed randomly into three different groups (haloperidol, d-amphetamine or vehicle).  Each animal received an injection 15 min prior to the start of every session from the beginning of interval training.  The subjects were trained in a Fixed Interval (FI) 16s schedule followed by training on a peak procedure in which 64s non-reinforced peak trials were intermixed with FI trials.  In a final test session all subjects were given vehicle injections and 10 consecutive non-reinforced peak trials to see if training under drug conditions altered the encoding of time.  The current study suggests that administration of drugs that modulate dopamine do not alter the encoding temporal durations but do acutely affect the initiation of responding.

Human neonates spend the majority of their time sleeping. Despite the limited waking hours available for environmental exploration, the first few months of life are a time of rapid learning about the environment. The organization of neonate sleep differs qualitatively from adult sleep, and the unique characteristics of neonatal sleep may promote learning. Sleep contributes to infant learning in multiple ways. First, sleep facilitates neural maturation, thereby preparing the infants to process and explore the environment in increasingly sophisticated ways. Second, sleep plays a role in memory consolidation of material presented while the infant was awake. Finally, emerging evidence indicates that infants process sensory stimuli and learn about contingencies in their environment even while asleep. As infants make the transition from reflexive to cortically mediated control, learned responses to physiological challenges during sleep may be critical adaptations to promote infant survival.

R. Epstein criticizes an article by P. Balsam and A. Bondy which urged caution in the use of reinforcement techniques. Epstein cites logic problems and notes the complexity of interventions. Balsam and Bondy respond and restate their basic argument. (CL)

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. Stimuli that accompany drug administration may come to evoke conditioned responses (CRs), and these CRs may be the basis for changes in drug efficacy. Specifically, this research shows that a dopamine antagonist, pimozide, changes response rates through the direct action of the drug but changes time perception through the CRs elicited by drug administration.

Food pecking in the ring dove is a skilled prehensile response that is similar to, but simpler than, many other prehensile responses. Previous work has shown that this response is initially poorly executed and requires experience for its accurate direction and coordination. The response involves two components: the thrusting of the bird's head toward food, and the opening and closure of the beak around food. Here, this second component, called gape, is followed through development with a precise measurement system. Four squabs moved through a similar sequence of three gape topographies, each of which is more efficient in picking up seed, during development. The present outcome, together with other work, argues for a substantial contribution of experience with pecking to the development of food pecking. We discuss the implications of these findings for understanding the ontogeny of motor control and for understanding how experience affects behavioral development.

The effects of food deprivation on ring dove squabs' begging and pecking was examined during the period of transition from dependent to independent feeding. Food-deprived squabs begged more, pecked more, and were fed more by their parents than nondeprived squabs. When deprived, young squab primarily beg for food and older squab primarily peck. This difference may arise from the relative efficiencies of the two feeding responses at different ages. Additionally, parental state exerted control over the amount the squab pecked and begged. Parental food deprivation affected squab pecking, probably because hungry parents pecked more themselves and fed squabs less. Squab begging was not affected by parental food deprivation. However, parental separation from squab affected squab begging, as parents previously without squab were more likely to feed begging squab than were parents who were not separated from squab. Parental separation from squab did not affect squab pecking. The changes in the endogenous and exogenous controls of squab feeding allow for a great deal of plasticity in the transition from dependent to independent feeding.

This series of experiments analyzes the role of learning in the development of pecking in ring dove squab. Experiment 1 showed that there is a high probability that parents will feed squab after a period of separation (Experiment 1). Such feedings may have been essential for producing the previous observation (Graf, Balsam, & Silver, 1985) that pecking develops normally if squab which have been separated from their parents are given a daily 20-min interaction with seed followed by an immediate return to their parents. Experiment 2 showed that exposure to seed followed by experimenter-provided feedings were sufficient for inducing adult pecking levels. Experiment 3 showed that general experience with conspecifics was not necessary for the development of pecking and that maturation alone could not account for the pecking observed in previous experiments. Experiment 4 showed that Pavlovian contingencies consisting of visual exposure to seed followed by feeding was sufficient to induce high levels of pecking. There did not appear to be an additional contribution of an operant contingency present when squab were allowed to both see and peck at seed prior to feedings in Experiment 5. However, squab must actually be given experience in handling and ingesting seeds before adult levels of pecking can be obtained. These results are discussed in terms of the developmental pathways whereby experience leads to adult behavior.

The effects of different shaping approximations on the topography of the rat's bar press were investigated in two experiments. Behavior was classified into discrete components, and changes in components and their sequential organization were analyzed. Experiment 1 examined response form early in training and found that specific components reinforced during shaping were incorporated into press sequences. Experiment 2 investigated how response form changed when a shaping contingency was relaxed later in training. Two topographies were selected for reinforcement, and both appeared in the press sequences of all subjects by the end of shaping. Subsequently, all variations of bar pressing were reinforced, and neither topography was necessary to satisfy the contingency. Although the frequency of the topographies reinforced during shaping declined for 3 of 4 subjects during this phase, the most frequent press sequence for 2 rats at the end of training included both unnecessary topographies. Variability in press topographies declined when all emitted variants were reinforced. However, all subjects emitted novel response forms throughout training. The results demonstrate that specific response-reinforcer contingencies influence response form by modulating component availability and organization.

In the random control procedure, responding to a conditioned stimulus (target CS) is prevented when the probability of unsignaled, unconditioned stimuli (USs) in the intertrial interval (ITI) is equal to the probability of the US in the presence of the target CS. Three experiments used an autoshaping procedure with White Carneaux pigeons to examine the effects of the temporal duration of signals for the ITI USs (cover CSs) and for concomitant periods of nonreinforcement. In Experiment 1, a short duration cover, but not a long duration cover, resulted in responding to the target CS. In Experiment 2, an explicit CS- cue during periods of nonreinforcement did not affect target acquisition. In Experiment 3, a long CS-, but not a short cover CS, was a sufficient condition for the acquisition of responding to the target CS. These results imply that the acquisition of responding to a target CS requires a discriminable period of nonreinforcement that is long relative to the target CS duration.

Two experiments are reported which investigate the speed of contextual conditioning in autoshaping. In both experiments, a procedure was employed in which ring doves were magazine trained in one context prior to the manipulation of background values in a second context. In Experiment 1, subjects were exposed to 4, 8, 64, 128, or 256 US-only presentations prior to autoshaping. Acquisition speed and maintained response measures were monotonically related to the number of pretraining trials. Subjects in Group 4 acquired the key-peck response fastest, and retardation was maximal within 64 pretraining trials. In Experiment 2, subjects given 20 pretraining trials were significantly more retarded than subjects given 2 pretraining trials, but only when pretraining and testing were conducted in the same context. Overall, the results of these experiments show that in autoshaping, contextual conditioning is very rapid; this demonstrates the plausibility of theoretical accounts of Pavlovian conditioning which assert that the development of the conditioned response depends on the associative values of both the CS and background stimuli.

In a series of three experiments the effects of variation in grain duration on automaintenance were evaluated. In the first experiment, key illumination was followed by grain only when pigeons did not peck the key. Each subject was exposed to 2-, 4-, and 8-second feeder durations in blocks of 10 sessions. Subjects pecked on a high percentage of trials at all feeder durations. The mean peck latency was shorter in the 8-second condition than in the two other conditions in five of six subjects. The conditional probability of pecking given successive keylight-grain pairings did not increase as the number of pairings increased. The second experiment was identical to the first, except that key pecking had no scheduled consequence. Under these conditions, all three subjects showed substantial responding. The recorded measures showed no systematic relationship to feeder duration in this study. In the third experiment, two different stimuli were followed by feeder presentations of either identical (2- or 8-second) or different (2- and 8-second) durations within each session. Subjects tended to respond sooner and with a higher overall rate in the presence of the stimulus associated with the longer feeder duration only when different feeder durations were presented within the same session. This result was confirmed by direct observation of the pigeons. The results of these experiments suggest that the effects of varying grain duration may be small, compared to the effects of varying other variables. The results also suggest that the location as well as the frequency of pecking may be an important measure in the analysis of factors controlling the pigeon's key peck.

In four experiments we investigated whether signaled and unsignaled US presentations resulted in differential context conditioning. Experiments 1 and 2 showed that the presence of a tone during grain presentation facilitated the formation of tone-food associations in pigeons. Experiment 2 also showed that the acquisition of associative value by the tone did not diminish associations between context and the unconditioned stimulus (US). Experiment 3 showed that signaled USs did not interfere with the acquisition of context-US associations, and Experiment 4 showed that even when the signal was extensively pretrained, context-US associations could not be blocked. The results of these experiments are inconsistent with conditioning models that require competition between cues and contexts for associative value.

In these studies, descriptive information on the diet and feeding behavior of ring dove squab is considered in the context of an analysis of the mechanisms underlying the development of eating. Experiment I shows that squab begin to peck at grain around Day 13 and both the rate and efficiency of pecking increase through Day 21 when the squab are weaned. Experiment II shows that squab reared without seed in their home cage do not develop normal levels of pecking unless exposure to seed is followed in close temporal proximity by interaction with parents. It is concluded that an association between some aspect of squab's interaction with seed and a parentally provided unconditioned stimulus is sufficient for normal pecking to develop. The nature of these associations and their contribution to the ontogeny of independent feeding are discussed.