Role of the anterior cingulate cortex in the control over behavior by Pavlovian conditioned stimuli in rats.

To investigate the contribution of the anterior cingulate cortex (ACC) to stimulus-reward learning, rats with lesions of peri- and postgenual ACC were tested on a variety of Pavlovian conditioning tasks. Lesioned rats learned to approach a food alcove during a stimulus predicting food, and responded normally for conditioned reinforcement. They also exhibited normal conditioned freezing and Pavlovian-instrumental transfer, yet were impaired at autoshaping. To resolve this apparent discrepancy, a further task was developed in which approach to the food alcove was under the control of 2 stimuli, only 1 of which was followed by reward. Lesioned rats were impaired, approaching during both stimuli. It is suggested that the ACC is not critical for stimulus-reward learning per se, but is required to discriminate multiple stimuli on the basis of their association with reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial geniculate lesions block amygdalar and cingulothalamic learning-related neuronal activity

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)+] to avoid a foot shock, and they learn to ignore a different tone (CS-) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CS+ than to the CS-. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas.     

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.     

Pedunculopontine tegmental nucleus lesions impair stimulus–reward learning in autoshaping and conditioned reinforcement paradigms.

The role of the pedunculopontine tegmental nucleus (PPTg) in stimulus–reward learning was assessed by testing the effects of PPTg lesions on performance in visual autoshaping and conditioned reinforcement (CRf) paradigms. Rats with PPTg lesions were unable to learn an association between a conditioned stimulus (CS) and a primary reward in either paradigm. In the autoshaping experiment, PPTg-lesioned rats approached the CS+ and CS– with equal frequency, and the latencies to respond to the two stimuli did not differ. PPTg lesions also disrupted discriminated approaches to an appetitive CS in the CRf paradigm and completely abolished the acquisition of responding with CRf. These data are discussed in the context of possible cognitive function of the PPTg, particularly in terms of lesion-induced disruptions of attentional processes that are mediated by the thalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.

The present study examined the effects of lesions of the central nucleus of the amygdala (CeA) on the acquisition of a new response with conditioned reinforcement (CR) and its potentiation by intra-accumbens infusions of d-amphetamine (1, 3, 10, and 20 μg/μl). Rats were trained to associate a light-plus-noise compound stimulus with the availability of a sucrose solution before receiving both bilateral ibotenic acid lesions of the CeA and cannulas implanted above the nucleus accumbens. Lesions of the central nucleus did not impair the performance of positively reinforced discriminated approach, nor did they impair the acquisition of a new response with conditioned reinforcement. However, the potentiation of responding with CR following intra-accumbens amphetamine was blocked in lesioned animals. These results are discussed in terms of the possible interactions between associative mechanisms in the amygdala and the mesolimbic dopamine projection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia

Gerbils learned to approach a spatial-olfactory stimulus that signaled access to their pairmate. Experiments 1 and 3 used a discrimination procedure in which 1 conditioned stimulus (the CS+) was presented immediately before access to the pairmate and another (the CS-) was presented alone. Both male and female gerbils came to approach the CS+ sooner than the CS- and spent more time near the CS+ than the CS-. Discrimination learning was facilitated by making the CS+ and CS- spatially distinct (Experiment 3). Learning also was demonstrated in male gerbils, using a between-subjects design with a single CS. Pairing the CS with the opportunity for social interaction resulted in greater approach to the CS within 10 trials than presenting the CS and social opportunity in an unpaired fashion (Experiment 2). These findings demonstrate social-affiliative learning in the Mongolian gerbil. Similarities and differences between these findings and sexual conditioning effects in other species are discussed.     

Disconnection of the amygdala central nucleus and the substantia innominata/nucleus basalis magnocellularis disrupts performance in a sustained attention task.

The basal forebrain cholinergic system is broadly implicated in the regulation of attention. Disruptions in the function of this system produce impairments in many attentional functions, including the performance of well-learned responses under increased attentional load and the surprise-induced enhancement of learning rate. Similarly, lesions of the amygdala central nucleus (CeA) have been found to impair attentional function in some circumstances. In the present article, the effects of lesions that disconnected CeA from the cholinergic substantia innominata/nucleus basalis magnocellularis (SI/nBM) on performance are examined in a modified 5-choice serial reaction time (5CSRT) task, thought to assess selective or sustained attention. The lesions impaired performance under conditions of increased attentional load, suggesting that a circuit that includes CeA and SI/nBM regulates these aspects of attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the central nucleus of the amygdala in olfactory heart rate conditioning.

The role of the central nucleus of the amygdala on olfactory heart rate conditioning in the infant rat was investigated. The conditioned stimulus (CS) consisted of a 10-s presentation of grape juice odor that was immediately followed by a 0.5-s, 0.35-mA subcutaneous shock. A sensitization control group was also run. Three days prior to testing, Ss received either bilateral electrolytic lesions of the central nucleus of the amygdala, sham lesions, or were left unperturbed. Results show that damage to the central nucleus of the amygdala severely impaired olfactory heart rate conditioning but that it had no deleterious effect on the heart rate orienting response to that stimulus or on the heart rate unconditioned response (UCR) to shock. Results are analogous to those in previous research on auditory heart rate conditioning and suggest that the central nucleus of the amygdala may constitute a necessary stage in the transduction of the CS into a cardiac conditioned response (CR) regardless of sensory modality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian conditioning of agonistic behavior in male threespine stickleback (Gasterosteus aculeatus)

The red coloration of male stickleback (Gasterosteus aculeatus) possesses signal value in male-male interactions. Therefore, it was predicted that males would learn to associate a red signal more readily than a green signal with a conspecific rival in a Pavlovian conditioning experiment. Males were presented red and green signal lights where one signal was always paired with presentation of a rival (excitatory conditioned stimulus, CS+) and one signal was never paired with presentation of a rival (nonreinforced stimulus, CS-). Males learned the task rapidly, showing conditioned approach and zigzag responses, but CS+ vs. CS- differentiation persisted, even after a prolonged extinction period. In addition, there were no differences in learning rates between fish trained to the red signal as the CS+ and fish trained to the green signal as the CS+. The results suggest that, although males may rapidly learn about rivals, they are not predisposed to associated red (over green) with the appearance of a rival under the conditions of this experiment. Because males must establish and maintain territories in order to nest and mate, learning about neighboring rivals may be an adaptive mechanism by which males more effectively defend their territories and thereby increase their reproductive fitness.     

Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: Implications for the neurobiology of emotion.

The effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on stimulus-reward learning were investigated with a novel Pavlovian autoshaping procedure in an apparatus allowing for the automated presentation of computer-graphic stimuli to rats (T. J. Bussey, J. L. Muir, & T. W. Robbins, 1994). White vertical rectangles were presented on the left or the right of a computer screen. One of these conditioned stimuli (the CS+) was always followed by the presentation of a sucrose pellet; the other, the CS–, was never followed by reward. With training, rats came to approach the CS+ more often than the CS–. Anterior cingulate cortex-lesioned rats failed to demonstrate normal discriminated approach, making significantly more approaches to the CS– than did sham-operated controls. Medial frontal cortex-lesioned rats acquired the task normally but had longer overall approach latencies. Posterior cingulate cortex lesions did not affect acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microinjection of morphine into the nucleus accumbens impairs contextual learning in rats.

A unilateral microinjection of morphine into the amygdala impaired fear conditioning to both a conditioned stimulus (CS) paired with shock and the context where shock occurred, whereas a microinjection of morphine into the nucleus accumbens (NA) spared fear conditioning to the CS but impaired, in a dose-dependent and receptor-specific manner, fear conditioning to the context. Morphine in the NA also spared extinction and latent inhibition of a CS but abolished the context specificity of these effects and eliminated the increase in discriminability that results from preexposure to a to-be-shocked context. The results identify a role for the NA in the processes by which rats learn about a context and are discussed in terms of an opioid disruption of either within-context associations or of attentional processes that contribute to such associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste-potentiated odor aversion learning: Role of the amygdaloid basolateral complex and central nucleus.

Examined the relative contributions of the amygdaloid basolateral complex (ABL) and central nucleus (CN) to taste-potentiated odor aversion (TPOA) learning, an associative learning task that is dependent on information processing in 2 sensory modalities. In Exp 1, rats with neurotoxic lesions of these systems were trained on the TPOA task by presenting a compound taste–odor conditioned stimulus (CS), which was followed by LiCl administration. Results showed that ABL damage caused an impairment in potentiated odor aversion learning but no deficit in the conditioned taste aversion. In contrast, rats with CN damage learned both tasks. Exp 2 examined the effects of ABL damage on TPOA and odor discrimination learning. The odor discrimination procedure used a place preference task to demonstrate normal processing of olfactory information. Results indicated that although ABL-lesioned animals were impaired on TPOA, there was no deficit in odor discrimination learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Observational fear conditioning in the acquisition and extinction of attentional bias for threat: An experimental evaluation.

Anxious persons show automatic and strategic attentional biases for threatening information. Yet, the mechanisms and processes that underlie such biases remain unclear. The central aim of the present study was to elucidate the relation between observational threat learning and the acquisition and extinction of biased threat processing by integrating emotional Stroop color naming tasks within an observational differential fear conditioning procedure. Forty-three healthy female participants underwent several consecutive observational fear conditioning phases. During acquisition, participants watched a confederate displaying mock panic attacks (UCS) paired with a verbal stimulus (CS+), but not with a second nonreinforced verbal stimulus (CS-). As expected, participants showed greater magnitude electrodermal and verbal-evaluative (e.g., distress, fear) conditioned responses to the CS+ over the CS- word. Participants also demonstrated slower color-naming latencies to CS+ compared to the CS- word following acquisition and showed attenuation of this preferential processing bias for threat following extinction. Findings are discussed broadly in the context of the interplay between fear learning and processing biases for threat as observed in persons suffering from anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitory learning tests of conditioned stimulus associability in rats with lesions of the amygdala central nucleus.

Normal rats showed faster inhibitory learning about a light conditioned stimulus (CS) if it had previously been an inconsistent predictor of a tone CS than if it had been a consistent predictor of the tone. In contrast, the inhibitory learning of rats with ibotenic acid lesions of the amygdala central nucleus (CN) was unaffected by the prior predictive value of the light. These results support claims that the CN is critical to surprise-induced enhancement of attentional processing of CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of the behavioural effects of R(+) 7-OH-DPAT infusions in the central and basolateral amygdala nuclei upon Pavlovian and instrumental conditioned appetitive behaviours

Dopaminergic cell bodies located within the ventral mesencephalon innervate the amygdaloid complex, a region critically involved in the attribution of affective significance to environmental stimuli. Recently, we have shown that post-session intra-amygdala administration of a D3 dopamine receptor agonist enhances selectively the acquisition of an appetitive conditioned response. In the present study, we have investigated the potential involvement of the central nucleus and the basolateral nuclei of the amygdala in mediating this effect. Thus, rats were trained to associate an arbitrary stimulus (CS+) with the availability of 10% sucrose reward. Post-session infusions of the D3 receptor-preferring agonist, R(+) 7-OH-DPAT, were made into either the central nucleus or basolateral nuclei. Acquisition of a conditioned approach response was enhanced by R(+) 7-OH-DPAT infusions within the central nucleus, but not within the basolateral nuclei. Drug infusions into either region failed to affect approach behaviour elicited by presentation of a control stimulus (CS-), explicitly unpaired with sucrose reward. The effects of pre-test infusions of R(+) 7-OH-DPAT on the instrumental properties of the stimuli were then determined. Rats were presented with two novel levers, depression of one lever resulted in presentation of the CS+, while presentation of the CS- was contingent upon depression of the other lever. Rates of response upon each lever as well as the ability of the conditioned stimuli subsequently to elicit conditioned approach behaviour were recorded. Data revealed a double dissociation of the effects of R(+) 7-OH-DPAT on the expression of the Pavlovian and instrumental properties of the reward-related stimulus. Thus, within the central nucleus R(+) 7-OH-DPAT dose-dependently attenuated expression of the conditioned approach response, but had no effect upon instrumental responding maintained by the conditioned reward. In contrast, within the basolateral nuclei, R(+) 7-OH-DPAT had no effect upon expression of conditioned approach behaviour, but abolished selectively the ability of the reward-associated stimulus to support the acquisition of a novel instrumental response. Hence, these data indicate that distinct regions of the amygdaloid complex process distinct aspects of conditioned appetitive behaviours.     

Brain systems mediating aversive conditioning: an event-related fMRI study

We have used event-related functional magnetic resonance imaging (fMRI) to characterize neural responses associated with emotional learning. Employing a classical conditioning paradigm in which faces were conditioned by pairing with an aversive tone (US), we compared responses evoked by conditioned (CS+) and nonconditioned (CS-) stimuli. Pairing 50% of the CS+ with the US enabled us to constrain our analysis to responses evoked by a CS+ not followed by a US. Differential evoked responses, related to conditioning, were found in the anterior cingulate and the anterior insula, regions with known involvement in emotional processing. Differential responses of the amygdalae were best characterized by a time by stimulus interaction indicating a rapid adaptation of CS+-specific responses in this region.     

Effects of reward timing information on cue associability are mediated by amygdala central nucleus.

The central nucleus of the amygdala (CeA) has been implicated in a range of associative learning phenomena often attributed to changes in attentional processing of events. Experiments using a number of behavioral tasks have shown that rats with lesions of CeA fail to show the enhancements of stimulus associability that are normally induced by the surprising omission of expected events. By contrast, in other tasks, rats with lesions of CeA show normal enhancements of associability when events are presented unexpectedly. In this experiment, we examined the effects of CeA lesions on changes in cue associability in a reward timing task. In sham-lesioned rats, the associability of cues that were followed by stimuli that provided reward timing information was maintained at higher levels than that of cues that were followed by uninformative stimuli. Rats with lesions of CeA failed to show this advantage. These results indicate that the role of CeA in the modulation of associability is not limited to cases of event omission. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Hippocampal lesions alter conditioning to conditional and contextual stimuli

The control of conditioned fear behaviour by a conditional stimulus (CS) and contextual stimuli (CXT) was compared in rats with lesions to the hippocampus (HPC) or neocortex (CO), and operated controls (OC). After classical fear conditioning in a distinctive context, rats were subsequently tested in the presence of the CS and CXT (CS + CXT), the CS alone (CS-only), or context alone (CXT-only). Two experiments were conducted in which conditioned fear was measured by an active avoidance response (experiment 1) or by response suppression (experiment 2). Groups did not differ in acquiring the conditioned fear response, as measured in the CS + CON test but, in both experiments, hippocampal (HPC) groups exhibited more conditioned fear behaviour than controls in the CXT-Only and CS-Only conditions. It was suggested that control rats conditioned the fear response to a stimulus complex that incorporated the CS and CTX. Rats with HPC lesions did not form this association between the stimulus elements; instead they segregated the CS and CXT and formed independent associations between the conditioned response (CR) and each component. In showing that HPC damage disrupts the process of forming associations between environmental stimuli and that the effect is not restricted to contextual cues, the results help to resolve apparently contradictory findings regarding the role of HPC in contextual information processing.     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning of a flavor aversion in rats by amygdala kindling.

Rats received 30 stimulations and 30 sham stimulations (the lead was attached to the subjects but no current was delivered) to the left basolateral amygdala in a quasirandom sequence. Stimulations were preceded by the presentation of 1 flavored solution conditional stimulus (CS+); sham stimulations were preceded by the presentation of another flavored solution, CS-. As kindled motor seizures developed, the rats began to consume significantly less of the CS+ than the CS- Moreover, at the end of the experiment, the rats consumed significantly less of the CS+ than the CS- during a 20-min conditioned flavor preference test in which both solutions were available simultaneously. These findings confirm and extend the recent report that interictal changes in defensive behavior can be conditioned by amygdalar kindling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)