Biomedical subjects

Peter C Holland

Publications and source records attributed to Peter C Holland.

At least 19 recordsLinked to original sources

PubMed2006

Learned contextual cue potentiates eating in rats.

Explicit cues associated with food consumption when hunger prevails will enhance eating when they are subsequently presented under conditions of satiety. Here we examined whether contextual conditioned stimuli (CSs) paired with consumption of food pellets while rats were food-deprived would enhance consumption of this food in rats that were not food-deprived. The conditioning context enhanced rats' consumption of the training food, but it did not change their consumption of the familiar, lab chow. These results show that the contextual CSs, like discrete cues, could modulate food consumption in a CS-potentiated eating paradigm. Furthermore, the data suggest that CS-potentiation of eating does not induce a general motivation to eat, akin to hunger, but instead more likely produces a more specific motivational state, akin to craving.

Animals↗

PubMed2006

Role of substantia nigra-amygdala connections in surprise-induced enhancement of attention.

Coding of prediction error by midbrain dopamine neurons has been examined extensively in the framework of associative learning theory. Most of this research has focused on the role of prediction error in determining the reinforcement value of unconditioned stimuli: poorly predicted ("surprising") outcomes are more effective reinforcers and produce a greater dopamine response than well predicted outcomes. However, surprise also enhances attention to cues that signal poorly predicted outcomes. Previous reports from our laboratories demonstrated that circuitry, including the amygdala central nucleus (CeA), the cholinergic neurons of the substantia innominata/nucleus basalis region, and their innervation of the posterior parietal cortex, is critical to these surprise-induced enhancements of attention in associative learning. The present study considered the origin of prediction error information important for the operation of this system by examining the effects of disrupting communication between the midbrain substantia nigra pars compacta (SNc) and the CeA. Rats received unilateral lesions of the SNc and lesions of the CeA in either the contralateral or ipsilateral hemisphere. Contralateral lesions eliminated the surprise-induced enhancement of attention and learning that was displayed by rats with ipsilateral control lesions. These results show that SNc-CeA communication is critical to mechanisms by which the coding of prediction error by midbrain dopamine neurons is translated into enhancement of attention and learning modulated by the cholinergic system.

Amygdala↗

PubMed2006

Different roles for amygdala central nucleus and substantia innominata in the surprise-induced enhancement of learning.

Within most modern learning theories, the discrepancy between expected and obtained outcomes ("prediction error" or "surprise") is a critical determinant of the acquisition of learned associations. The results of studies from many laboratories show that the surprising omission of an expected event may enhance attention to stimuli that remain present, such that subsequent learning about those stimuli is enhanced. A series of reports from our laboratories demonstrated that these surprise-induced enhancements of stimulus associability depend on circuitry that includes the amygdala central nucleus (CeA), the cholinergic neurons in the sublenticular substantia innominata/nucleus basalis magnocellularis (SI/nBM), as well as certain cortical projections of these latter neurons. In this study, we found very different roles for CeA and SI/nBM in surprise-induced enhancements of stimulus associability. In four experiments that used transient inactivation techniques, we found that surprise-induced enhancement of subsequent learning about a stimulus depended on intact CeA function at the time of surprise but not when more rapid learning was subsequently expressed. In contrast, normal SI/nBM function was critical to the expression of enhanced learning but was not necessary when surprise was induced. These data suggest that these two components of the so-called "extended amygdala" serve distinct roles in the encoding and retrieval of information used in modulating attention to stimuli in associative learning. Additional circuitry linking these brain regions may also be important in the maintenance of that information.

Amygdala↗

PubMed2006

Limitations on representation-mediated potentiation of flavour or odour aversions.

Odour aversion learning is often potentiated in the presence of flavour stimuli. Establishment of an aversion to an odour is greater when an odour + flavour compound is paired with illness than when the odour alone is paired with illness. Holland (1983) showed that under some circumstances auditory or olfactory stimuli previously paired with flavours may also potentiate odour aversion learning. The present experiments examined limitations on this representation-mediated potentiation of aversion learning. The results indicated that conditioned stimuli (CSs) that activate representations of potentiating cues are themselves immune to potentiation by other CS-activated representations, but remain susceptible to potentiation by their real stimulus associates.

Animals↗

PubMed2006

Substantia nigra pars compacta is critical to both the acquisition and expression of learned orienting of rats.

Novel events produce characteristic orienting responses (ORs), which typically habituate rapidly with repeated stimulus presentation. However, they may re-emerge if those stimuli become predictors of biologically significant events. This acquisition of conditioned ORs may reflect a broader range of enhancements in top-down attentional processing of cues that predict important consequences. Previous research from this laboratory showed that a neural circuit that includes the amygdala central nucleus (CeA), substantia nigra pars compacta (SNc) and dorsolateral striatum (DLS) is essential for the learning and expression of one example of conditioned orienting, the rearing of rats to visual stimuli paired with food. Other studies showed that the CeA is critical to the acquisition of these conditioned ORs, but not their expression, and that normal DLS function is required for the expression of previously acquired conditioned ORs, but not for learning itself. The experiments reported here considered the roles of the SNc in conditioned orienting by examining the effects of transient inactivation of the SNc during the acquisition of new associations and during the expression of previous learning. SNc function was critical to both the acquisition and expression of conditioned ORs but not to the display of unconditioned ORs or the learning and expression of conditioned responses directed to the food source. Together with our previous findings, these results suggest that the SNc is trained by the CeA during learning and maintains acquired information so that it may modulate DLS sensory-motor function at the time of action.

Animals↗

PubMed2005

A neural systems analysis of the potentiation of feeding by conditioned stimuli.

Associative learning processes play many important roles in the control of food consumption. Although these processes can complement regulatory mechanisms in the control of eating by providing opportunities for the anticipation of upcoming needs, they may also contribute to inappropriate or pathological consumption patterns by overriding internal regulatory signals. In this article, we first review some of the ways in which associative learning can contribute to the control of feeding, and then describe a neural systems analysis of a simple animal model of the control of feeding by Pavlovian-conditioned stimuli (CSs). Food-sated rats increase their food consumption after presentation of CSs that were previously paired with food while the rats were food-deprived. This cue-potentiated feeding is independent of conditioned approach responses, and is at least somewhat specific to the foods associated with those CSs. A series of studies that used neuroanatomical tract tracing, immediate early gene expression, and neurotoxic disconnection lesion techniques implicated circuitry that includes the basolateral complex of the amygdala, the lateral hypothalamus, and the medial prefrontal cortex, but not the amygdala central nucleus, nucleus accumbens, or lateral orbitofrontal cortex, in cue-potentiated feeding. These studies also showed dissociations between cue-potentiated feeding and other learned motivational phenomena that are known to depend on function of amygdala systems. The data suggest that cue-potentiated feeding is uniquely mediated by cortical and amygdalar neurons that directly target the lateral hypothalamus, and thus gain access to hypothalamic neuropeptide and other systems involved in the promotion and suppression of eating.

Animals↗

PubMed2005

Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating.

Experimental animals that are trained to associate a cue with food consumption when hunger prevails will subsequently consume a greater amount of food when that cue is presented under conditions of satiety. Previously, we showed that this phenomenon of conditioned potentiation of feeding is abolished by a neurotoxic lesion that encompasses the basolateral (BL), basomedial (BM), and lateral (LA) nuclei of the amygdala (AMY) and by disconnection of this region and lateral hypothalamus (LHA). Here, we combined immediate-early gene (IEG) and tract-tracing methods to map functional AMY-LHA circuitry that is engaged when potentiated feeding is produced by pavlovian conditioning. Sated rats were assessed for food consumption in the presence of a cue that was paired previously with food (CS+), or in the presence of another cue that was never paired with food (CS-), in two consecutive tests temporally arranged for activation of the effector IEGs Arc (activity-regulated cytoskeletal protein) and Homer 1a. We examined the selective induction of the IEGs by tests with CS+ or CS- presentations in AMY neurons that project to LHA, as identified with the retrograde tracer FluoroGold. Using the same labeling methods, we also examined neurons in several other forebrain regions, including the prefrontal cortex and nucleus accumbens, that receive strong inputs from BL/BM/LA nuclei and, in turn, innervate the LHA. Our results indicate that a cue that has acquired the ability to promote eating in sated rats (CS+) strongly activates a functional network formed by direct pathways from the BL/BM and orbitomedial prefrontal cortex to the LHA.

Amygdala↗

PubMed2005

Enhanced conditioning produced by surprising increases in reinforcer value are unaffected by lesions of the amygdala central nucleus.

In many experimental settings, lesions of the central nucleus of the amygdala (CN) interfere with surprise-induced enhancement of event processing. In those settings, surprise was produced by omitting an expected event. This experiment examined the effects of CN lesions on enhanced learning after surprise was induced by presenting an unexpected event. After extensive light-food pellet pairings, a light-noise compound was paired with food pellets, and a sucrose solution was unexpectedly delivered after the food. Relative to a control condition, this manipulation enhanced the formation of associations between the auditory conditioned stimulus and food, in both sham- and CN-lesioned rats. These results indicate that CN circuitry implicated in surprise-induced increases in event processing is preferentially engaged when expected events are omitted, and not when unexpected events are presented.

Amygdala↗

PubMed2005

Lesions of orbitofrontal cortex impair rats' differential outcome expectancy learning but not conditioned stimulus-potentiated feeding.

Patients with damage to the orbitofrontal cortex (OFC) display various impairments in cognitive and affective function, including a reduced ability to use information about the consequences of their actions to guide their behavior. In this study, rats with neurotoxic lesions of the OFC failed to use specific expectancies about outcomes to guide their learning of an instrumental discrimination task. In contrast, lesioned rats were unimpaired in a measure of learned motivational function, the potentiation of feeding under conditions of food satiation, by a conditioned stimulus that had been paired with food while the rats were food deprived. Notably, performance of both of these tasks has been shown to depend on the function of the basolateral amygdala (BLA), a region that is richly interconnected with the OFC. Thus, the present results are consistent with the view that the acquisition and use of specific outcome expectancies to guide behavior critically involve a neural system that includes the BLA and the OFC, but they indicate that certain motivational properties acquired by cues on the basis of appetitive learning involve BLA circuitry apart from the OFC.

Animals↗

PubMed2005

Role of amygdalo-nigral circuitry in conditioning of a visual stimulus paired with food.

The amygdala central nucleus (CeA) plays an important part in associative learning. Although most research has focused on functions of its descending projections to brainstem areas involved in autonomic and somatomotor responses, the ascending projections of CeA also play critical roles in learning. For example, a CeA-nigrostriatal pathway is important for acquiring orienting responses (ORs) to conditioned stimuli (CSs) that signal food delivery. In this study, the function of this CeA-nigrostriatal pathway in appetitive conditioning of rats was considered in more detail. In experiment 1, we combined anatomical tracing and methods for detecting neuronal activation to examine whether CeA neurons that project to the substantia nigra pars compacta (SNc) are activated by a visual CS for food. After injection of the retrograde tracer Fluoro-Gold (FG) into SNc, the rats received pairings of a visual CS with food. After a test with the CS alone, the brains were prepared to assess FG labeling and CS-induced Fos expression in CeA with immunohistochemical procedures. Colocalization of Fos and FG in CeA neurons was visualized with confocal-fluorescence microscopy. The CS induced Fos expression in CeA, and a majority of these Fos-positive neurons were also FG positive, indicating activation of the CeA-SNc pathway by the CS. In experiment 2, lesions that disconnected CeA and SNc prevented the acquisition of conditioned ORs but did not affect the acquisition of conditioned food-related responses or the display of unconditioned ORs. These experiments demonstrate a role for amygdalo-nigral circuitry in learned modulation of attention to signals for biologically significant events.

Amygdala↗

PubMed2005

Variations in unconditioned stimulus processing in unblocking.

Three experiments examined the mechanisms by which downward shifts in reinforcer value influence learning in appetitive unblocking procedures. The downward shift was accomplished by omitting the 2nd of a 2-reinforcer sequence (food-food or food-sucrose). Performance of normal rats was compared with that of rats with lesions of the central nucleus of the amygdala, which are thought to interfere with surprise-induced enhancements of event processing. The results suggested that, in normal rats, omission of the 2nd reinforcer enhanced processing of the 1st reinforcer rather than processing of the conditioned stimuli and that lesions of the central nucleus eliminated this enhancement. The roles of reinforcement error signals in conditioning are discussed.

Amygdala↗

PubMed2005

Amygdala central nucleus function is necessary for learning, but not expression, of conditioned auditory orienting.

In Pavlovian appetitive conditioning, rats often acquire 2 classes of conditioned responses: those whose form is determined by the reinforcer, and those whose form is determined by characteristics of the conditioned stimulus (CS). Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function during pairings of an auditory CS with food prevented the acquisition of conditioned orienting responses specific to auditory CSs, whereas food-related conditioned behaviors were acquired normally. Neither inactivation nor posttraining neurotoxic lesions of the central nucleus affected the expression of previously acquired conditioned orienting. Thus, although the central nucleus is critical to the acquisition of information required for conditioned orienting to auditory cues, it is not needed for maintaining this information for later use.

Amygdala↗

PubMed2005

Orbitofrontal lesions impair use of cue-outcome associations in a devaluation task.

The orbitofrontal cortex (OFC) has been implicated in the use of outcome expectancies to guide behavior. The present study used a devaluation task to examine this function. Rats first received light-food pairings followed by food-toxin pairings designed to devalue the food. After either excitotoxic or sham OFC lesions, responding to the light was reassessed. Sham-lesioned rats showed reduced responding to the light relative to behavioral controls, which had received food and toxin unpaired. In contrast, OFC-lesioned rats showed no such reductions. Combined with previous data (C. L. Pickens, M. P. Saddoris, B. Setlow, M. Gallagher, P. C. Holland, & G. Schoenbaum, 2003), these results indicate that the OFC is critical for the maintenance of information about the current incentive value of reinforcers or the use of that information to guide behavior.

Animal Feed↗

PubMed2005

Amount of training effects in representation-mediated food aversion learning: no evidence of a role for associability changes.

Rats acquired aversions to food pellets when a previously trained signal for that food was paired with a toxin, but only after minimal signal-food training. After extensive signal-food training, signal-toxin pairings had no effect on food consumption even after manipulations that enhanced the associability of the signal. By contrast, conditioned responding to the signal retained its sensitivity to devaluation of the food reinforcer by food-toxin pairings after extensive training. These results suggest that the nature of associatively activated event representations changes over the course of training.

Animals↗

PubMed2004

Amygdala-frontal interactions and reward expectancy.

Recent evidence indicates that networks including the amygdala and prefrontal cortex provide a key interface between affect and cognition. Converging evidence from rodents, humans, and non-human primates indicates that interconnections between the basolateral complex of the amygdala and the orbitofrontal cortex are crucial to the formation and use of expectancies of reinforcers in the guidance of goal-directed behavior.

Amygdala↗

PubMed2004

Conditioning and cognition.

Animals' abilities to use internal representations of absent objects to guide adaptive behavior and acquire new information, and to represent multiple spatial, temporal, and object properties of complex events and event sequences, may underlie many aspects of human perception, memory, and symbolic thought. In this review, two classes of simple associative learning tasks that address these core cognitive capacities are discussed. The first set, including reinforcer revaluation and mediated learning procedures, address the power of Pavlovian conditioned stimuli to gain access, through learning, to representations of upcoming events. The second set of investigations concern the construction of complex stimulus representations, as illustrated in studies of contextual learning, the conjunction of explicit stimulus elements in configural learning procedures, and recent studies of episodic-like memory. The importance of identifying both cognitive process and brain system bases of performance in animal models is emphasized.

Animals↗

PubMed2004

Relations between Pavlovian-instrumental transfer and reinforcer devaluation.

Relations between posttraining reinforcer devaluation and Pavlovian-instrumental transfer were examined in 2 experiments. When a single reinforcer was used, extended training of the instrumental response increased transfer but reduced devaluation effects. When multiple instrumental reinforcers were used, both reinforcer-specific transfer and devaluation effects were less influenced by the amount of instrumental training. Finally, although reinforcer devaluation decreased both Pavlovian conditioned responses and baseline instrumental responding, it had no effect on either single-reinforcer or reinforcer-specific transfer. These results indicate that transfer and reinforcer devaluation can reflect different aspects of associative learning and that the nature of associative learning can be influenced by parameters such as the amount of training and the use of multiple reinforcers.

Analysis of Variance↗

PubMed2004

Amygdala central nucleus function is necessary for learning but not expression of conditioned visual orienting.

When exposed to pairings of a visual stimulus with food delivery, rats normally acquire both conditioned orienting responses directed toward the visual stimulus and conditioned food-related responses. Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function before each conditioning session prevented the acquisition of conditioned orienting responses, whereas food-related behaviors were acquired normally. By contrast, neither inactivation nor neurotoxic lesions of central nucleus affected the expression of previously acquired conditioned orienting responses. Thus, the central nucleus is apparently not critical to the maintenance of information required for conditioned orienting, but instead is necessary for memory storage elsewhere. Specialized roles for components of a circuit for conditioned orienting, which includes the central nucleus, the substantia nigra, and dorsolateral striatum, are discussed.

Amygdala↗