A mathematical analysis on the biological zero problem in laser Doppler flowmetry

Whilst neurons within the lateral hypothalamus are well known to be responsive to the presentation of previously learned associative stimuli, the consolidation of a Pavlovian association is thought to depend in large part upon other brain regions, including the amygdala. The present study addressed this assumption directly, by examining the effect of post-session infusions of sulpiride within the lateral hypothalamus upon the acquisition of a conditioned approach response in an appetitive differential conditioning task. Subjects were exposed to an initially neutral stimulus (CS+), which immediately preceded the availability of a 10% sucrose reward (US). A second, control stimulus (CS ) was also presented. but never in close temporal proximity to the US. The number and duration of alcove approaches were recorded. Immediately following each training session, subjects were infused bilaterally with sulpiride (0, 0.5, 5 microg) in the vicinity of the perifornical region of the lateral hypothalamus. Sulpiride dose-dependently enhanced the rate of acquisition of a conditioned approach response to presentation of the CS+, but was without affect upon approach behaviour during CS(-) or US presentations. Thus, 0.5 microg sulpiride facilitated at an early stage (session 2 onwards) the number of alcove approaches to the CS+, while 5 microg sulpiride enhanced to a greater extent the duration of conditioned approach, particularly during later sessions. A subsequent locomotor test using 0.5 mg/kg d-amphetamine indicated that repeated infusions of the higher dose sulpiride (5 microg), but not the lower dose (0.5 microg), resulted in behavioural sensitisation to administration of the psychomotor stimulant. Acquisition of a novel conditioned instrumental response was not affected by previous exposure to sulpiride. These data suggest that dopamine-sensitive neurons within the lateral hypothalamus may play a significant role in the acquisition of appetitive Pavlovian associations.     

Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear

The amplitude of the acoustic startle response is reliably enhanced when elicited in the presence of bright light (light-enhanced startle) or in the presence of cues previously paired with shock (fear-potentiated startle). Light-enhanced startle appears to reflect an unconditioned response to an anxiogenic stimulus, whereas fear-potentiated startle reflects a conditioned response to a fear-eliciting stimulus. We examine the involvement of the basolateral nucleus of the amygdala, the central nucleus of the amygdala, and the bed nucleus of the stria terminalis in both phenomena. Immediately before light-enhanced or fear-potentiated startle testing, rats received intracranial infusions of the AMPA receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (3 microg) or PBS. Infusions into the central nucleus of the amygdala blocked fear-potentiated but not light-enhanced startle, and infusions into the bed nucleus of the stria terminalis blocked light-enhanced but not fear-potentiated startle. Infusions into the basolateral amygdala disrupted both phenomena. These findings indicate that the neuroanatomical substrates of fear-potentiated and light-enhanced startle, and perhaps more generally of conditioned and unconditioned fear, may be anatomically dissociated.     

Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala

The amygdala has long been thought to be involved in emotional behaviour, and its role in anxiety and conditioned fear has been highlighted. Individual amygdaloid nuclei have been shown to project to various cortical and subcortical regions implicated in affective processing. Here we show that some of these nuclei have separate roles in distinct mechanisms underlying conditioned fear responses. Rats with lesions of the central nucleus exhibited reduction in the suppression of behaviour elicited by a conditioned fear stimulus, but were simultaneously able to direct their actions to avoid further presentations of this aversive stimulus. In contrast, animals with lesions of the basolateral amygdala were unable to avoid the conditioned aversive stimulus by their choice behaviour, but exhibited normal conditioned suppression to this stimulus. This double dissociation demonstrates that distinct neural systems involving separate amygdaloid nuclei mediate different types of conditioned fear behaviour. We suggest that theories of amygdala function should take into account the roles of discrete amygdala subsystems in controlling different components of integrated emotional responses.     

Facilitation of appetitive Pavlovian conditioning by d-amphetamine in the shell, but not the core, of the nucleus accumbens.

The effects of postsession d-amphetamine within subregions of the ventral and dorsal striatum on appetitive Pavlovian learning were assessed. Rats acquired a conditioned approach response on presentation of a stimulus predictive of 10% sucrose solution (unconditioned stimulus [US]), but not during equally frequent presentations of a stimulus uncorrelated with the US. In Experiment 1, postsession d-amphetarnine infusions enhanced acquisition of conditioned responding, with no effect on control measures. In Experiment 2, rats received postsession d-amphetamine in the accumbens shell or core. Shell infusions facilitated conditioning; core infusions did not. In Experiment 3, dorsomedial striatal infusions of d-amphetamine also were ineffective. In sum, dopaminergic activation within the shell, but not the core, of the nucleus accumbens facilitates the acquisition of a Pavlovian association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Targeted deletion of the GluR-1 AMPA receptor in mice dissociates general and outcome-specific influences of appetitive rewards on learning.

The authors assessed the hypothesis that deletion of the GluR-1 subtype of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor in mice disrupts the associative activation of a sensory-specific representation of an appetitive reward. In Experiment 1, mice received training on a Pavlovian-instrumental transfer task. In the test stage, conditioned stimulus (CS) presentations enhanced instrumental actions in both groups. However, this effect was specific to the action that shared the same outcome as the CS in wild-type (WT), but not GluR-1-/-, mice. In Experiment 2, the mice were trained on a heterogeneous instrumental chain in which rewards were obtained for emitting 1 response (R1, that was distal to reward delivery), followed by a 2nd response (R2, that was proximal to reward delivery). A change in general motivational state (from hungry to sated) reduced the number of R2 responses in both groups. In contrast, an outcome-specific satiety treatment produced a selective decline in R1 responding only in WT mice. The results support the hypothesis that GluR-1 deletion impairs the associative activation of a representation of the sensory-specific incentive motivational properties of an appetitive reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdaloid block fear-potentiated startle and shock sensitization of startle.

Destroyed cell bodies in the lateral and basolateral amygdaloid nuclei by local infusion of N-methyl-{d}-aspartate. Adjacent areas, such as the central amygdaloid nucleus, were largely spared. Lesions were carried out before training and testing (Exp 1) or after training but before testing (Exp 2). In both cases, the lesions completely blocked fear-potentiated startle (increased acoustic startle in the presence of a light previously paired with footshock). They also blocked increased startle after a series of footshocks, provided they damaged the most anterior part of the basolateral nucleus. It is suggested that the lateral or basolateral amygdaloid nuclei (or both) relay visual information to the central amygdaloid nucleus, which is also critical for fear-potentiated startle. In addition, activation of the most anterior part of the basolateral nucleus may be critical for processing shock information during fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquired appetitive responding to intravenous nicotine reflects a Pavlovian conditioned association.

Recent research examining Pavlovian appetitive conditioning has extended the associative properties of nicotine from the unconditioned stimulus or reward to include the role of a conditional stimulus (CS), capable of acquiring the ability to evoke a conditioned response. To date, published research has used presession extravascular injections to examine nicotine as a contextual CS in that appetitive Pavlovian drug discrimination task. Two studies in the current research examined whether a nicotine CS can function discretely, multiple times within a session using passive iv infusions. In Experiment 1, rats readily acquired a discrimination in conditioned responding between nicotine and saline infusions when nicotine was selectively paired with sucrose presentations. In Experiment 2, rats were either trained with nicotine paired with sucrose or explicitly unpaired with sucrose. The results showed that rats trained with explicitly unpaired nicotine and sucrose did not increase dipper entries after the infusions. Nicotine was required to be reliably paired with sucrose for control of conditioned responding to develop. Implications of these findings are discussed in relation to tobacco addiction, learning theory, and pharmacology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an impaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS + significantly less often than controls, failing to discriminate between the CS + and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prolonged enhancement of REM sleep produced by carbachol microinjection into the amygdala

The effect on sleep organization of carbachol microinjected into different amygdaloid nuclei was analysed in 12 cats. Single carbachol doses of 8 micrograms in 0.50 microliter saline were delivered unilaterally or bilaterally into the central, basal, lateral or basolateral amygdaloid nucleus. Carbachol administration into the central nucleus induced a prolonged (5 days) enhancement of both REM sleep and its preceeding slow wave sleep episodes with PGO waves (sommeil phasique a ondes lentes, SPHOL), which was more pronounced following bilateral than unilateral carbachol administration. However, neither SPHOL nor REM sleep changes were produced by administration of carbachol into the other amygdaloid nuclei. We conclude that cholinergic activation of the central amygdaloid nucleus produces a long-term facilitation of REM sleep occurrence.     

CS modality transfer of two-way avoidance in rats with central and basolateral amygdala lesions

Post-lesion acquisition of two-way avoidance and subsequent transfer to two warning signals (conditioned stimulus, CS) of different modality were investigated in 60 rats. In Experiment I the animals were originally trained with less salient (darkness) CS, then transferred to more salient compound (darkness and white noise), and finally to white noise CS. The opposite arrangement of the conditioned stimuli (CSi) during the subsequent stages was employed in Experiment II. In control animals, avoidance acquisition was faster and the intertrial responding (ITR) rate lower with the auditory than with the visual CS. Lesioned rats learned avoidance responses more slowly, independently of CS modality. The transfer to other CSi revealed dramatic between-group difference in the level and consistency of avoidance response, shuttle-box latencies and ITR rate. In control animals, transfer to more salient CSi enhanced avoidance performance, whereas change to less salient CS decreased it. Rather small changes in shuttle-box performance and consistency of avoidance response due to CS modality were seen in rats with the basolateral lesions. In contrast, central nucleus injury caused a strong deterioration in the avoidance transfer, especially when the visual CS followed the acoustic one. The results indicate differential involvement of the basolateral and central amygdala nuclei in stimulus-processing mechanisms of instrumental defensive behavior.     

Basal forebrain cholinergic lesions enhance conditioned approach responses to stimuli predictive of food

This study examined the effects of lesions to different neuronal populations within the basal forebrain on reward-related learning. Rats received bilateral alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or quinolinate lesions that preferentially destroy the cholinergic nucleus basalis magnocellularis (NBM) or noncholinergic ventral pallidal neurons, respectively. Both lesions enhanced conditioned approach responses to stimuli predictive of food but did not increase the locomotor stimulating effect of d-amphetamine. Although both lesions disrupted the discriminative control over behavior by a conditioned stimulus, they did not impair the subsequent acquisition of instrumental responding with conditioned reinforcement (CR). Indeed, both lesions were associated with an increased responding with CR following intra-accumbens infusions of d-amphetamine (0, 1, 3, 10, and 20 microg). Quinolinate lesions also increased responses on an inactive control lever. Neither lesion altered consummatory responses to food or sucrose. Results suggest that NBM lesions may disrupt the balance between cortical and subcortical dopamine levels, and/or produce a deficit in attentional mechanisms that is manifested as increased responding to specific stimuli.     

Hyperphagia induced by GABAA receptor-mediated inhibition of the nucleus accumbens shell: Dependence on intact neural output from the central amygdaloid region.

To investigate the role of corticolimbic input in modulating feeding-related nucleus accumbens (Acb) circuitry, researchers temporarily deactivated sites within the basolateral amygdaloid complex (BLA) or central amygdaloid region (CeA) via GABAA agonist (muscimol) infusions and measured feeding responses following muscimol infusions into the Acb shell. Hyperphagia elicited by intra-Acb shell muscimol was not altered by coinfusions of intra-BLA muscimol. In contrast, muscimol infusions into the CeA dose-dependently reduced feeding elicited either by intra-Acb shell GABAA receptor stimulation or by food deprivation and produced a syndrome of forepaw treading. Intra-CeA tetrodotoxin infusions also blocked intra-Acb shell muscimol-induced hyperphagia. Hence, feeding elicited by intra-Acb shell GABAA receptor stimulation requires intact neural output from the CeA but not the BLA. (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.     

Measurement of digestive disorders in the piglet at weaning and related risk factors

Inputs from the amygdaloid and extraamygdaloid areas terminate in various divisions of the central nucleus. To elucidate the interconnections between the different regions of the central nucleus and its connectivity with the other amygdaloid areas, we injected the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L) into the capsular, lateral, intermediate, and medial divisions of the central nucleus in rat. There were a number of labeled terminals near the injection site within each division. The intrinsic connections between the various divisions of the central nucleus were organized topographically and originated primarily in the lateral division, which projected to the capsular and medial divisions. Most of the connections were unidirectional, except in the capsular division, which received a light reciprocal projection from its efferent target, the medial division. The intermediate division did not project to any of the other divisions of the central nucleus. Extrinsic projections from the central nucleus to the other amygdaloid nuclei were meager. Light projections were observed in the parvicellular division of the basal nucleus, the anterior cortical nucleus, the amygdalohippocampal area, and the anterior amygdaloid area. No projections to the contralateral amygdala were found. These data show that the central nucleus has a dense network of topographically organized intradivisional and interdivisional connections that may integrate the intraamygdaloid and extraamygdaloid information entering the different regions of the central nucleus. The sparse reciprocal connections to the other amygdaloid nuclei suggest that the central nucleus does not regulate the other amygdaloid regions but, rather, executes the responses evoked by the other amygdaloid nuclei that innervate the central nucleus.     

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)     

Cortical substrates of taste aversion learning: Involvement of dorsolateral amygdaloid nuclei and temporal neocortex in taste aversion learning.

Examined the involvement of the central (CE), lateral (LA), and basolateral (BL) amygdaloid nuclei and the temporal neocortices (area 20) in conditioned taste-aversion (CTA) learning. 40 adult male Long-Evans hooded rats received bilateral electrolytic lesion placements in the CE, LA, BL, or the temporal neocortices. 16 controls received scalp and meningeal incisions only. Following recovery, Ss were habituated to a restricted drinking schedule with distilled water. Animals then received CTA conditioning, with LiCl used both as the CS and as the UCS. Anterograde degeneration histologies were performed on all brain tissue to evaluate relations between CTA learning deficits and axonal pathology induced by lesion placements. Results indicate that destruction of the CE, LA, or temporal neocortex impaired CTA acquisition, but damage induced to the BL amygdaloid nucleus did not. Anatomical observations indicated that degeneration of amygdalofugal and/or corticofugal projections to the convolutions of the olfactory tubercle (medial), subthalamic nucleus, and the parabrachial complex was correlated with CTA learning deficits. Findings suggest that destruction of the dorsolateral amygdaloid nuclei and/or the temporal neocortices may produce CTA learning deficits by affecting olfactory, gustatory, and/or gastrointestinal processing in various portions of the forebrain. (51 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Operant and Pavlovian control of visual stimulus orienting and food-related behaviors in rats with lesions of the amygdala central nucleus.

The effects of superimposing operant reward and omission contingencies on 2 Pavlovian conditioned responses evoked by a visual conditioned stimulus paired with food were examined in rats with lesions of the amygdala central nucleus (CN). In sham-lesioned rats, the frequency of an orienting response, rearing, was increased by reward contingencies and decreased by omission contingencies, compared with yoked Pavlovian controls. In contrast, in CN-lesioned rats, rearing was not affected by either operant contingency and occurred at lower levels with Pavlovian procedures alone than in sham-lesioned rats. Nevertheless, CN-lesioned and sham-lesioned rats showed similar increases in the frequency of conditioned food-cup behavior with reward contingencies, similar decreases with omission contingencies, and similar levels of that response with Pavlovian procedures. (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)     

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)     

Conditioned responses of monkey locus coeruleus neurons anticipate acquisition of discriminative behavior in a vigilance task

Impulse activity was recorded extracellularly from noradrenergic neurons in the nucleus locus coeruleus of three cynomolgus monkeys performing a visual discrimination (vigilance) task. For juice reward, the subjects were required to release a lever rapidly in response to an improbable target stimulus (20% of trials) that was randomly intermixed with non-target stimuli presented on a video display. All locus coeruleus neurons examined were phasically and selectively activated by target stimuli in this task. Other task events elicited no consistent response from these neurons (juice reward, lever release, fix spot stimuli, non-target stimuli). With reversal of the task contingency, locus coeruleus neurons ceased responding to the former target stimuli, and began responding instead to the new target (old non-target) stimuli. In addition, the latency of locus coeruleus response to target stimuli increased after reversal (by about 140 ms) in parallel with a similar increase in the latency of the behavioral response. These results indicate that the conditioned locus coeruleus responses reflect stimulus meaning and cognitive processing, and are not driven by physical sensors attributes. Notably, the reversal in locus coeruleus response to stimuli after task reversal occurred rapidly, hundreds of trials before reversal was expressed in behavioral responses. These findings indicate that conditioned responses of locus coeruleus neurons are plastic and easily altered by changes in stimulus meaning, and that the locus coeruleus may play an active role in learning the significance of behaviorally important stimuli.