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Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation.

Consistent with the importance of the hippocampus in learning more complex stimulus relations, but not in simple associative learning, the dorsal hippocampus has commonly been implicated in classical fear conditioning to context, but not to discrete stimuli, such as a tone. In particular, a specific and central role in contextual fear conditioning has been attributed to mechanisms mediated by dorsal hippocampal N-methyl-D-aspartate (NMDA)-type glutamate receptors. The present study characterized the effects of blockade or tonic stimulation of dorsal hippocampal NMDA receptors by bilateral local infusion of the noncompetitive NMDA receptor antagonist MK-801 (dizocilpine maleate; 6.25 microg/side) or of NMDA (0.7 microg/side), respectively, on classical fear conditioning to tone and context in Wistar rats. Freezing was used to measure conditioned fear. Regardless of whether conditioning was conducted with tone-shock pairings or unsignaled footshocks (background or foreground contextual conditioning), both NMDA and MK-801 infusion before conditioning resulted in reduced freezing during subsequent exposure to the conditioning context. Freezing during subsequent tone presentation in a new context, normally resulting from conditioning with tone-shock pairings, was not impaired by MK-801 but was strongly reduced by NMDA infusion before conditioning; this freezing was also reduced by NMDA infusion before tone presentation (in an experiment involving NMDA infusions before conditioning and subsequent tone presentation to assess the role of state-dependent learning). It was assessed whether unspecific infusion effects (altered sensorimotor functions, state dependency) or infusion-induced dorsal hippocampal damage contributed to the observed reductions in conditioned freezing. Our data suggest that formation of fear conditioning to context, but not tone, requires NMDA receptor-mediated mechanisms in the dorsal hippocampus. As indicated by the effects of NMDA, some dorsal hippocampal processes may also contribute to fear conditioning to tone. The role of the dorsal hippocampus and local NMDA receptor-mediated processes in fear conditioning to tone and context is discussed in comparison with ventral hippocampal processes.

Acoustic Stimulation↗

Contextual control over the expression of fear in rats conditioned under a benzodiazepine.

RATIONALE: Benzodiazepines disrupt fear conditioning, but this disruption is context-specific; if rats have been conditioned under a benzodiazepine, their fear is recovered if they are tested in a different context. The present experiments investigated how the conditioning context controls fear in rats conditioned under a benzodiazepine. OBJECTIVES: The experiments had three aims: (1) to replicate the finding that fear is recovered when rats are tested in a different context, (2) to test whether the conditioning context reduces fear generally or only for the specific stimulus conditioned in that context and (3) to test whether latent inhibition of the conditioning context reduces its control over fear. METHODS: Rats were injected with the benzodiazepine midazolam (1.25 mg/kg) or saline and exposed to a conditioned stimulus (CS) and shock in a distinctive chamber. Latent inhibition of the chamber was induced by extensively preexposing the rats to the chamber. The day after conditioning, fear was assessed by presenting the CS while rats were in either the conditioning chamber or a different chamber. RESULTS: The midazolam-induced reduction of fear was reversed (i.e. fear was partially recovered) if rats were tested in the different context, and was completely prevented if the conditioning context had been latently inhibited. These two effects were not additive since, when the conditioning context had been latently inhibited, rats showed less fear in the different context than in the conditioning context. CONCLUSIONS: We argue that midazolam does not disrupt conditioning, but imbues the conditioning context with control over retrieval of the CS-shock association. In this regard, the effects of midazolam closely parallel those of extinction.

Animals↗

Neurotoxic lesions of the dorsal and ventral hippocampus impair acquisition and expression of trace-conditioned fear-potentiated startle in rats.

Pavlovian delay conditioning, in which a conditioned stimulus (CS) and unconditioned stimulus (US) co-terminate, is thought to reflect non-declarative memory. In contrast, trace conditioning, in which the CS and US are temporally separate, is thought to reflect declarative memory. Hippocampal lesions impair acquisition and expression of trace conditioning measured by the conditioned freezing and eyeblink responses, while having little effect on the acquisition of delay conditioning. Recent evidence suggests that lesions of the ventral hippocampus (VH) impair conditioned fear under conditions in which dorsal hippocampal (DH) lesions have little effect. In the present study, we examined the time-course of fear expression after delay and trace conditioning using the fear-potentiated startle (FPS) reflex, and the effects of pre- and post-training lesions to the VH and DH on trace-conditioned FPS. We found that both delay- and trace-conditioned rats displayed significant FPS near the end of the CS relative to the unpaired control group. In contrast, trace-conditioned rats displayed significant FPS throughout the duration of the trace interval, whereas FPS decayed rapidly to baseline after CS offset in delay-conditioned rats. In experiment 2, both DH and VH lesions were found to significantly reduce the overall magnitude of FPS compared to the control group, however, no differences were found between the DH and VH groups. These findings support a role for both the DH and VH in trace fear conditioning, and suggest that the greater effect of VH lesions on conditioned fear might be specific to certain measures of fear.

Animals↗

Pharmacological dissociation of trace and long-delay fear conditioning in young rats.

In most studies comparing trace and delay conditioning, CS duration is kept constant across training conditions but the interstimulus interval (ISI), the time from CS onset to US onset, is confounded. In the infrequently used long-delay condition, however, ISI is kept constant across the trace and delay conditions but CS duration varies. A recent study reported that trace and long-delay fear conditioning have the same developmental trajectory, with both emerging later in development than standard-delay conditioning (). Past studies have shown that trace conditioning is mediated by the cholinergic system; given the parallel developmental emergence of trace and long-delay conditioning, the present study examined whether the cholinergic system also mediates long-delay conditioning. Two experiments, both involving Sprague-Dawley-derived rats and using freezing as a measure of learned fear, showed that the cholinergic system is critically involved in trace conditioning but is not involved in long-delay conditioning. Specifically, pre-training injections of the muscarinic receptor antagonist scopolamine impaired acquisition of a CS-US association in 32-day-old rats trained with a trace procedure but had no effect on rats this age trained with a long-delay procedure (Experiment 1). Similarly, pre-training injections of physostigmine, a cholinesterase inhibitor, enhanced acquisition of trace conditioning in 25-day-old rats but had no effect on long-delay conditioning in rats this age (Experiment 2). Taken together, the results indicate that despite the similarities between trace and long-delay conditioning in terms of developmental emergence and level of conditioned responding, they are mediated by different physiological systems.

Age Factors↗

Working memory and fear conditioning.

Previous studies of associative learning implicate higher-level cognitive processes in some forms of classical conditioning. An ongoing debate is concerned with the extent to which attention and awareness are necessary for trace but not delay eye-blink conditioning [Clark, R. E. & Squire, L. R. (1998) Science 280, 77-81; Lovibond, P. F. & Shanks, D. (2002) J. Exp. Psychol. Anim. Behav. Processes 28, 38-42]. In trace conditioning, a short interval is interposed between the termination of the conditioned stimulus (CS) and the onset of the unconditioned stimulus (US). In delay conditioning, the CS and US overlap. We here investigate the extent to which human classical fear conditioning depends on working memory. Subjects had to carry out an n-back task, requiring tracking an item 1 or 2 back in a sequentially presented list of numbers, while simultaneously being tested for their ability to associate auditory cues with shocks under a variety of conditions (single-cue versus differential; delay versus trace; no task versus 0-, 1-, and 2-back). Differential delay conditioning proved to be more resilient than differential trace conditioning but does show a reduction due to task interference similar in slope to that found in trace conditioning. Explicit knowledge of the stimulus contingency facilitates but does not guarantee trace conditioning. Only the single-cue delay protocol shows conditioning during the more difficult working memory task. Our findings suggest that the larger the cognitive demands on the system, the less likely conditioning occurs. A postexperimental questionnaire showed a positive correlation between conditioning and awareness for differential trace conditioning extinction.

Adolescent↗

Discrete cues paired with naloxone-precipitated withdrawal from acute morphine dependence elicit conditioned withdrawal responses.

Acute bolus doses of morphine induce a state of acute opioid dependence as measured by naloxone-precipitated withdrawal. Repeated morphine and precipitated withdrawal experience further enhances naloxone-induced withdrawal severity, partly because of direct neuroadaptation to repeated morphine, and partly because of conditioned associations of context and withdrawal experience. To determine whether a discrete tone/light conditioned stimulus could elicit conditioned withdrawal responses in acute dependence, rats trained on a fixed-ratio-15 operant schedule for food reward received morphine (5.6 mg/kg) 4x at daily or weekly intervals, with each morphine injection followed at 4 h by naloxone (1.0 mg/kg) and an operant session. The conditioned stimulus was presented to a Paired group after each naloxone injection. Separate control groups experienced the conditioned stimulus either at a different time of the day or on a different day of the week than naloxone (Unpaired), received naloxone without any conditioned stimulus exposure [Paired-no conditioned stimulus (Paired-NO CS)] or received vehicle instead of naloxone before conditioned stimulus presentation (NaI-Naive). On the test day, all rats received vehicle before conditioned stimulus exposure. The conditioned stimulus alone reliably suppressed responding in Paired groups relative to control conditions with either daily or weekly intervals between conditioning sessions. The administration of morphine 4 h before conditioned stimulus exposure on the test day was not necessary to observe conditioned withdrawal. Thus, conditioned withdrawal is reliably established to discrete cues associated with naloxone-precipitated withdrawal from acute, infrequent (weekly) opioid exposure.

Acoustic Stimulation↗

Changes in central delay of soleus H reflex after facilitatory or inhibitory conditioning in humans.

1. Central delay (CD) changes after facilitatory or inhibitory conditioning of the soleus H reflex have been investigated in a group of normal subjects as a function of the conditioning and test stimulus intensities and also as a function of the Hmax/Mmax ratio. Both facilitation and inhibition of the reflex response have been obtained by conditioning stimulation of the ipsilateral tibial nerve at suitable conditioning-test stimulus intervals. CD changes have been extrapolated from the variations of the time interval between afferent and efferent neural volleys underlying the H reflex, directly recorded from the sciatic nerve. 2. The CD was significantly decreased by facilitatory and increased by inhibitory conditioning. Facilitatory CD changes were positively related to test stimulus strength (at a given conditioning stimulus intensity) and negatively related to conditioning stimulus strength (at a given test stimulus intensity). Both trends were reversed after inhibitory conditioning. The effectiveness of facilitatory conditioning was positively related to the individual Hmax/Mmax ratio whereas a negative relationship could be observed after inhibitory conditioning. 3. Also, the "conditioning threshold" (the minimal conditioning stimulus strength affecting the reflex size) and the "maximal conditioning effect" (the conditioning stimulus intensities leading to either the saturation of the facilitatory effect or the suppression of the reflex response) were significantly related to the Hmax/Mmax ratio. 4. We suggest that temporal changes in the H reflex pathway after facilitatory or inhibitory conditioning stimuli depend both on the size of the motoneuronal pool underlying the reflex response, as determined by the test stimulus intensity, and on the individual excitability of the motoneuronal pool, as defined by the Hmax/Mmax ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A quantitative analysis of sensitivity to the conditioned reinforcing value of terminal-link stimuli in a concurrent-chains schedule.

Pigeons were exposed to a concurrent-chains schedule in which a single variable-interval 30-s schedule was used in the initial links and fixed-time schedules were used in the terminal links. Three types of keylight conditions were used in the terminal links. In the first condition, different delays were associated with different keylight stimuli (cued condition). In the second condition, different delays were associated with the same stimulus, either a blackout (uncued blackout condition) or a white key (uncued white condition). Paired values of terminal-link fixed-time schedules differed by a constant ratio of 3:1, while the absolute value of delays was varied from 3 s to 54 s. The results showed that choice proportions for the shorter of two delays increased when the absolute size of the delays was increased for all keylight conditions. Further, the choice proportions for the shorter delay increased from the uncued blackout condition, to the uncued white condition, to the cued condition. A modified version of Fantino's (1969) delay-reduction model (expressed as a function relating the response ratio to the delay-reduction ratio) can be applied to these data by showing that sensitivity to delay reduction increased from the uncued blackout condition, to the uncued white condition, to the cued condition. Thus, the present study demonstrated that a modified version of the delay-reduction model can be used to assess quantitative differences in the terminal-link keylight condition in terms of sensitivity to delay reduction (i.e., the conditioned reinforcing value of the terminal-link keylight stimuli).

Animals↗

Physiological and subjective responses in the elderly when using floor heating and air conditioning systems.

The purpose of this study was to investigate the effects of a floor heating and air conditioning system on thermal responses of the elderly. Eight elderly men and eight university students sat for 90 minutes in a chair under the following 3 conditions: air conditioning system (A), floor heating system (F) and no heating system (C). The air temperature of sitting head height for condition A was 25 degrees C, and the maximum difference in vertical air temperature was 4 degrees C. The air and floor temperature for condition F were 21 and 29 degrees C, respectively. The air temperature for condition C was 15 degrees C. There were no significant differences in rectal temperature and mean skin temperature between condition A and F. Systolic blood pressure of the elderly men in condition C significantly increased compared to those in condition A and F. No significant differences in systolic blood pressure between condition A and F were found. The percentage of subjects who felt comfortable under condition F was higher than that of those under condition A in both age groups, though the differences between condition F and A was not significant. Relationships between thermal comfort and peripheral (e.g., instep, calf, hand) skin temperature, and the relationship between thermal comfort and leg thermal sensation were significant for both age groups. However, the back and chest skin temperature and back thermal sensation for the elderly, in contrast to that for the young, was not significantly related to thermal comfort. These findings suggested that thermal responses and physiological strain using the floor heating system did not significantly differ from that using the air conditioning system, regardless of the subject age and despite the fact that the air temperature with the floor heating system was lower. An increase in BP for elderly was observed under the condition in which the air temperature was 15 degrees C, and it was suggested that it was necessary for the elderly people to heat the room somehow in winter. Moreover, it is particularly important for elderly people to avoid a decrease in peripheral skin temperature, and maintain awareness of the warmth of peripheral areas, such as the leg, in order to ensure thermal comfort.

Adult↗

The direction of the conditioned natural killer cell response can be re-directed with indomethacin and/or handling.

We have used the pairing of camphor odor conditioned stimulus (CS) and injection of poly I:C unconditioned stimulus (US) in a short 3 day single trial conditioning paradigm. Conditioning was done by exposing mice to the CS/US combination on day 0 and reexposing the conditioned animals to the CS on day 2. This results in a conditioned augmentation of the natural killer (NK) cell response. Indomethacin treatment and/or handling stress induced by simply measuring rectal temperature was found to dramatically alter the direction of the conditioned NK cell response. Conditioning of indomethacin treated mice produced a conditioned suppression of the NK cell response mimicking a conditioned tolerance response. If handling stress was superimposed on day 2 the conditioned suppression response was replaced by a conditioned augmentation of the NK cell response. Even with one trial conditioning, drugs and handling stress can serve as additional cues to alter the direction of the conditioned response. The studies also show that the conditioning of the fever response is independent of conditioning of the NK cell response.

Animals↗

Prevalence, expenditures, and complications of multiple chronic conditions in the elderly.

BACKGROUND: The prevalence, health care expenditures, and hospitalization experiences are important considerations among elderly populations with multiple chronic conditions. METHODS: A cross-sectional analysis was conducted on a nationally random sample of 1 217 103 Medicare fee-for-service beneficiaries aged 65 and older living in the United States and enrolled in both Medicare Part A and Medicare Part B during 1999. Multiple logistic regression was used to analyze the influence of age, sex, and number of types of chronic conditions on the risk of incurring inpatient hospitalizations for ambulatory care sensitive conditions and hospitalizations with preventable complications among aged Medicare beneficiaries. RESULTS: In 1999, 82% of aged Medicare beneficiaries had 1 or more chronic conditions, and 65% had multiple chronic conditions. Inpatient admissions for ambulatory care sensitive conditions and hospitalizations with preventable complications increased with the number of chronic conditions. For example, Medicare beneficiaries with 4 or more chronic conditions were 99 times more likely than a beneficiary without any chronic conditions to have an admission for an ambulatory care sensitive condition (95% confidence interval, 86-113). Per capita Medicare expenditures increased with the number of types of chronic conditions from $211 among beneficiaries without a chronic condition to $13 973 among beneficiaries with 4 or more types of chronic conditions. CONCLUSIONS: The risk of an avoidable inpatient admission or a preventable complication in an inpatient setting increases dramatically with the number of chronic conditions. Better primary care, especially coordination of care, could reduce avoidable hospitalization rates, especially for individuals with multiple chronic conditions.

Age Factors↗

Selecting target conditions for quality of care improvement in vulnerable older adults.

OBJECTIVE: To identify a set of geriatric conditions as optimal targets for quality improvement to be used in a quality measurement system for vulnerable older adults. DESIGN: Discussion and two rounds of ranking of conditions by a panel of geriatric clinical experts informed by literature reviews. METHODS: A list of 78 conditions common among vulnerable older people was reduced to 35 on the basis of their (1) prevalence, (2) impact on health and quality of life, (3) effectiveness of interventions in improving mortality and quality of life, (4) disparity in the quality of care across providers and geographic areas, and (5) feasibility of obtaining the data needed to test compliance with quality indicators. A panel of 12 experts in geriatric care discussed and then ranked the 35 conditions on the basis of the same five criteria. We then selected 21 conditions, based on panelists' iterative rankings. Using available national data, we compiled information about prevalence of the selected conditions for community-dwelling older people and older nursing home residents and estimated the proportion of inpatient and outpatient care attributable to the selected conditions. RESULTS: The 21 conditions selected as targets for quality improvement among vulnerable older adults include (in rank order): pharmacologic management; depression; dementia; heart failure; stroke (and atrial fibrillation); hospitalization and surgery; falls and mobility disorders; diabetes mellitus; end-of-life care; ischemic heart disease; hypertension; pressure ulcers; osteoporosis; urinary incontinence; pain management; preventive services; hearing impairment; pneumonia and influenza; vision impairment; malnutrition; and osteoarthritis. The selected conditions had mean rank scores from 1.2 to 3.8, and those excluded from 4.6 to 6.9, on a scale from 1 (highest ranking) to 7 (lowest ranking). Prevalence of the selected conditions ranges from 10 to 50% among community-dwelling older adults and from 25 to 80% in nursing home residents for the six most common selected conditions. The 21 target conditions account for at least 43% of all acute hospital discharges and 33% of physician office visits among persons 65 years of age and older. Actual figures must be higher because several of the selected conditions (e.g., end-of-life care) are not recorded as diagnoses. CONCLUSIONS: Twenty-one conditions were selected as targets for quality improvement in vulnerable older people for use in a quality measurement system. The 21 geriatric conditions selected are highly prevalent in this group and likely account for more than half of the care provided to this group in hospital and ambulatory settings.

Aged↗

Projection, stereotyping, and the perception of chronic medical conditions.

OBJECTIVES: To test the hypotheses that people with chronic medical conditions are more likely than those without chronic medical conditions to project personal characteristics onto the population with chronic medical conditions, and that people without chronic medical conditions are more likely to stereotype those with chronic medical conditions. METHODS: The study is a secondary analysis of the 2000 Chronic Illness and Caregiving survey conducted by Harris Interactive Inc. using linear and probit regressions. RESULTS: The hypothesis that persons with chronic medical conditions project their characteristics onto the population of those with chronic medical conditions is strongly supported. The hypothesis that persons without chronic medical conditions stereotype the population of those with chronic medical conditions is weakly supported. DISCUSSION: The findings imply that characterizations of persons with chronic medical conditions vary more among those with chronic medical conditions than among those without, and that those without chronic medical conditions have more homogeneous representations. This difference between those who have chronic medical conditions and those who do not implies a potential for greater variation in support for the particulars of policies addressing chronic medical conditions among those with chronic medical conditions.

Chronic Disease↗

Sexual selection, genetic architecture, and the condition dependence of body shape in the sexually dimorphic fly Prochyliza xanthostoma (Piophilidae).

The hypothesis that sexual selection drives the evolution of condition dependence is not firmly supported by empirical evidence, and the process remains poorly understood. First, even though sexual competition typically involves multiple traits, studies usually compare a single sexual trait with a single "control" trait, ignoring variation among sexual traits and raising the possibility of sampling bias. Second, few studies have addressed the genetic basis of condition dependence. Third, even though condition dependence is thought to result from a form of sex-specific epistasis, the evolution of condition dependence has never been considered in relation to intralocus sexual conflict. We argue that condition dependence may weaken intersexual genetic correlations and facilitate the evolution of sexual dimorphism. To address these questions, we manipulated an environmental factor affecting condition (larval diet) and examined its effects on four sexual and four nonsexual traits in Prochyliza xanthostoma adults. As predicted by theory, the strength of condition dependence increased with degree of exaggeration among male traits. Body shape was more condition dependent in males than in females and, perhaps as a result, genetic and environmental effects on body shape were congruent in males, but not in females. However, of the four male sexual traits, only head length was significantly larger in high-condition males after controlling for body size. Strong condition dependence was associated with reduced intersexual genetic correlation. However, homologous male and female traits exhibited correlated responses to condition, suggesting an intersexual genetic correlation for condition dependence itself. Our findings support the role of sexual selection in the evolution of condition dependence, but reveal considerable variation in condition dependence among sexual traits. It is not clear whether the evolution of condition dependence has mitigated or exacerbated intralocus sexual conflict in this species.

Animals↗

Conditioning of behavioural effects produced by an intermediate dose of apomorphine: hypokinesia, ptosis and stereotypies.

Apomorphine, in an intermediate dose (0.18 mg/kg s.c.) decreased dopamine turnover and produced signs generally attributed to a decrease in dopaminergic neurotransmission, e.g. ptosis and yawning, as well as signs of an increased stimulation of dopamine receptors in dopaminoceptive target neurones, e.g. stereotyped sniffing. In contrast, the former signs were exclusively observed after smaller doses and the latter after larger doses of apomorphine. Since it had been shown in previous studies that these signs, except yawning, could be conditioned in association with discriminative stimuli in the environment, the present study using conditioning experiments with this intermediate dose aimed at determining, 1. the time course of each conditioned response, 2. the interaction of conditioned and unconditioned responses, and 3. the conditions under which hypokinesia occurred. In each series, conditioned animals were compared with pseudoconditioned controls. Rats were conditioned for 8 days with apomorphine, and on day 9, treated with saline in presence of the conditional stimuli (a test cage in combination with acoustic and olfactory stimuli). In contrast to pseudoconditioned controls, ptosis and stereotyped behaviour were observed in conditioned rats, sometimes occurring alternatingly. These signs closely resembled the direct, unconditioned pharmacological effects. In addition, akinesia occurred after conditioning, although it was never manifest as a pure drug response, nor during the conditioning period. In contrast, yawning was observed in pseudoconditioned as well as in conditioned rats, although slightly more frequently in the former animals. Subsequently, the rats were again conditioned (or pseudoconditioned) on days 10-14 with apomorphine and both groups tested with the same dose (0.18 mg/kg) of apomorphine in the presence of the conditioned stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Blocking and nonsimultaneous compounds: comparison of responding during compound conditioning and testing.

Three blocking experiments were run using a conditional emotional response procedure with rats as subjects. In each experiment, following initial conditioning to a light stimulus, blocking rats were conditioned to a compound in which a short-duration (30-second) noise was superimposed on the terminal portion of the longer-duration light. In Experiment 1, the light was always three minutes in duration; in Experiment 2, the light was switched from a constant (three-minute) to a variable (0.5-5.0 minute) duration at the start of compound conditioning; in Experiment 3, the light was variable in duration throughout conditioning. Control rats received the same compound conditioning experiences as the blocking rats but did not receive prior conditioning to the light by itself. These temporal manipulations had strong and systematic influence on the rats' pattern of responding during compound conditioning. Most notably, experience with a constant-duration light resulted in both blocking and compound animals showing little conditional suppression to the early conditional stimulus portion of light by itself, followed by strong conditional suppression to the terminal 30 seconds of light plus noise. When testing was done with the noise in isolation subsequent to compound conditioning, however, an equally strong blocking effect was obtained across all the temporal manipulations. In all cases, the blocking animals showed much less conditional suppression to the noise than did the compound control animals. This lack of correspondence between the rats' responding during compound conditioning and their response to the noise by itself is theoretically puzzling. The confounding effect of inhibition of delay may provide at least a partial explanation of this pattern of results.

Acoustic Stimulation↗

Selective attention and Pavlovian conditioning.

The present results show that the common practice of using self-indexing conditioned stimuli (CSs) in research on Pavlovian conditioning is a major source of experimental bias. The typical stimulus used is either a light flash or a sound pulse in a light/sound-shielded chamber. Under these conditions the onset characteristics of the CS signal totally predominate over the durational characteristic, i.e. the pattern information. Thus a visual pattern presented as a CS in a dark chamber is confounded with a brightness change from darkness to light. In the first experiment, animals were conditioned with a brightness CS using a self-indexing signal paradigm. When tested for specificity of the conditioning, they showed complete transfer of learning to either a visual pattern or even an auditory CS. These findings indicated that the traditional conditioning paradigm is biased towards non-specific sensory learning. The second experiment showed that specific sensory conditioning is critically dependent on selective attention mechanisms. When the onset characteristics of the CS signal were de-emphasized by the use of equal energy background illumination in the intertribal interval (ITI) during conditioning, the animals were not able to feature extract either the onset or the durational component of the CS signal from the ITI background despite prolonged training. It was only by starting with conditioning that was initially anchored to the CS onset characteristics that a perceptual fade-in procedure would bias attention to feature extract the durational characteristics of the CS. Thus conditioning occurred only when the rabbit's attention was directed to detection of the gratings display without any associated changes in visual albedo. Perhaps the most important finding of the present experiments is that the use of self-indexing CS signals in Pavlovian conditioning inevitably introduces non-specific sensory processing involving multiple sensory input pathways in the conditioning. This inherent uncertainty of the sensory input pathways presents a problem for clarifying the role of sensory pathways in the neural mechanisms of NM conditioning. In addition, the use of self-indexing CSs inevitably leads to an underestimation of the role of forebrain mechanisms in Pavlovian conditioning.

Acoustic Stimulation↗

Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation.

Isolating rats immediately after conditioning impairs contextual but not auditory-cue fear conditioning. The reported experiments examine the involvement of brain interleukin-1beta (IL-1beta) in the impairment in contextual fear conditioning caused by social isolation. As measured by the conditioned freezing response, 5 h of social isolation after conditioning, impaired contextual but not auditory-cue fear conditioning in adult male Sprague-Dawley rats. Social isolation for 1 or 3 h after conditioning also increased IL-1beta protein in the hippocampus and cerebral cortex. No differences in IL-1beta protein levels were found in the pituitary or the hypothalamus. Intracerebroventricular (ICV) IL-1 receptor antagonist (IL-1ra) given after conditioning prevented the impairment in contextual fear conditioning caused by isolation. ICV IL-1ra had no effect on auditory-cue fear conditioning in these same animals, nor did it affect the level of contextual fear conditioning displayed by home cage controls. Like isolation, ICV IL-1beta (10 or 20 ng) after conditioning also impaired contextual but not auditory-cue fear conditioning. These results suggest that increased levels of brain IL-1beta play a role in producing the impairment in contextual fear conditioning produced by social isolation. These findings also add to the generality of the idea that stressors induce IL-1beta activity in the brain and that IL-1beta may play physiological roles in the uninjured brain.

Acoustic Stimulation↗