Single Conditioning Session Research Articles

Pavlovian-based neurofeedback enhances meta-awareness of mind-wandering

Absorption in mind-wandering (MW) may worsen our mood and can cause psychological disorders. Researchers indicate the possibility that meta-awareness of MW prevents these mal-effects and enhances favorable consequences of MW, such as boosting creativity; thus, meta-awareness has attracted psychological and clinical attention. However, few studies have investigated the nature of meta-awareness of MW, because there has been no method to isolate and operate this ability. Therefore, we propose a new approach to manipulate the ability of meta-awareness. We used Pavlovian conditioning, tying to it an occurrence of MW and a neutral tone sound inducing the meta-awareness of MW. To perform paired presentations of the unconditioned stimulus (neutral tone) and the conditioned stimulus (perception accompanying MW), we detected participants’ natural occurrence of MW via electroencephalogram and a machine-learning estimation method. The double-blinded randomized controlled trial with 37 participants found that a single 20-min conditioning session significantly increased the meta-awareness of MW as assessed by behavioral and neuroscientific measures. The core protocol of the proposed method is real-time feedback on participants’ neural information, and in that sense, we can refer to it as neurofeedback. However, there are some differences from typical neurofeedback protocols, and we discuss them in this paper. Our novel classical conditioning is expected to contribute to future research on the modulation effect of meta-awareness on MW.

Aversive Conditioning of Spatial Position Sharpens Neural Population-Level Tuning in Visual Cortex and Selectively Alters Alpha-Band Activity.

Processing capabilities for many low-level visual features are experientially malleable, aiding sighted organisms in adapting to dynamic environments. Explicit instructions to attend a specific visual field location influence retinotopic visuocortical activity, amplifying responses to stimuli appearing at cued spatial positions. It remains undetermined both how such prioritization affects surrounding nonprioritized locations, and if a given retinotopic spatial position can attain enhanced cortical representation through experience rather than instruction. The current report examined visuocortical response changes as human observers (N = 51, 19 male) learned, through differential classical conditioning, to associate specific screen locations with aversive outcomes. Using dense-array EEG and pupillometry, we tested the preregistered hypotheses of either sharpening or generalization around an aversively associated location following a single conditioning session. Competing hypotheses tested whether mean response changes would take the form of a Gaussian (generalization) or difference-of-Gaussian (sharpening) distribution over spatial positions, peaking at the viewing location paired with a noxious noise. Occipital 15 Hz steady-state visual evoked potential responses were selectively heightened when viewing aversively paired locations and displayed a nonlinear, difference-of-Gaussian profile across neighboring locations, consistent with suppressive surround modulation of nonprioritized positions. Measures of alpha-band (8-12 Hz) activity were differentially altered in anterior versus posterior locations, while pupil diameter exhibited selectively heightened responses to noise-paired locations but did not evince differences across the nonpaired locations. These results indicate that visuocortical spatial representations are sharpened in response to location-specific aversive conditioning, while top-down influences indexed by alpha-power reduction exhibit posterior generalization and anterior sharpening.SIGNIFICANCE STATEMENT It is increasingly recognized that early visual cortex is not a static processor of physical features, but is instead constantly shaped by perceptual experience. It remains unclear, however, to what extent the cortical representation of many fundamental features, including visual field location, is malleable by experience. Using EEG and an aversive classical conditioning paradigm, we observed sharpening of visuocortical responses to stimuli appearing at aversively associated locations along with location-selective facilitation of response systems indexed by pupil diameter and EEG alpha power. These findings highlight the experience-dependent flexibility of retinotopic spatial representations in visual cortex, opening avenues toward novel treatment targets in disorders of attention and spatial cognition.

Significant Acute Response of Brain-Derived Neurotrophic Factor Following a Session of Extreme Conditioning Program Is Correlated With Volume of Specific Exercise Training in Trained Men.

Several studies have demonstrated an acute and chronic increase of brain-derived neurotrophic factor (BDNF) in relation to different types of physical exercise. Currently, many individuals seek physical training strategies that present different types of stimulation and volume/intensity. Thus, the extreme conditioning methodology has gained great notoriety in the scientific and non-scientific environment. Knowing that BDNF values increase in an effort-dependent manner, it is necessary to study the effects of this strategy on BDNF levels. This study aimed to evaluate the acute response of BDNF in trained men submitted to an extreme conditioning program (ECP) session. Ten volunteers underwent an acute ECP session using the “as many reps as possible” (WOD-AMRAP) method, including three types of exercise (clean, wall ball and double or single-unders) for 9 min. BDNF was measured in the plasma, being collected baseline and immediately after the session. Total load of the clean exercise was five times greater than wall ball exercise (p < 0.05; 2096.1 ± 387.4 kg vs 415.8 ± 81.03 kg), which influenced little in the total load (p < 0.05, 2511.9 ± 358.52 kg) used. For the total volume, practitioners averaged 1.7 times more repetitions in the wall ball exercise compared to clean (46.2 ± 9 vs 29.5 ± 3.8 repetitions). The volunteers averaged 75.7 ± 12.6 double-unders repetitions, bringing the total volume of training to 151.4 ± 23.7 repetitions. Regarding the BDNF values, there was a significant difference (p = 0.05) between the pre- vs post-moments (11209.85 ± 1270.4 vs 12132.96 ± 1441.93 pg/ml). Effect size for this change as moderate (ES = 0.79). We found a positive correlation between total volume of clean exercise and delta BDNF values (p = 0.049). In conclusion, a single extreme conditioning session, through the practice of the WOD-AMRAP method, is capable of increasing the acute concentrations of plasma BDNF. In practical terms, we may suggest that future studies evaluate the effect of ECP as a strategy in the treatment of disorders associated with central degenerative changes.

Context-Dependent Passive Avoidance Learning in the Terrestrial SlugLimax

The terrestrial slug Limax has been used as a model animal for studying the neural mechanisms underlying associative olfactory learning. The slug also innately exhibits negative phototactic behavior using its eyes. In the present study, we developed an experimental paradigm for quantification of slug's negative phototaxis behavior, and investigated whether the nature of the negative phototaxis can be modified by learning experience. The experimental set-up consists of light and dark compartments, between which the slug can move freely. During conditioning, the slug was placed in the light compartment, and an aversive stimulus (quinidine sulfate solution) was applied when it reached the dark compartment. After a single conditioning session, the time to reach the dark compartment significantly increased when it was tested following 24 hr or one week. Protein synthesis inhibition immediately following the conditioning impaired the memory retention at one week but not at 24 hr. The retrieval of the memory was context-dependent, as the time to reach the dark compartment did not significantly increase if the slug was placed on a floor with a different texture in the memory retention test. If the aversive stimulus was applied when the slug was in the light compartment, the time to reach the dark compartment did not increase after 24 hr. This is the first report demonstrating the capability of the slug to form context-dependent passive avoidance memory that can be established in a single conditioning session.

Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization

Generalization of fear from previously threatening stimuli to novel but related stimuli can be beneficial, but if fear overgeneralizes to inappropriate situations it can produce maladaptive behaviors and contribute to pathological anxiety. Appropriate fear learning can selectively facilitate early sensory processing of threat-predictive stimuli, but it is unknown if fear generalization has similarly generalized neurosensory consequences. We performed in vivo optical neurophysiology to visualize odor-evoked neural activity in populations of periglomerular interneurons in the olfactory bulb 1 day before, 1 day after, and 1 month after each mouse underwent an olfactory fear conditioning paradigm designed to promote generalized fear of odors. Behavioral and neurophysiological changes were assessed in response to a panel of odors that varied in similarity to the threat-predictive odor at each time point. After conditioning, all odors evoked similar levels of freezing behavior, regardless of similarity to the threat-predictive odor. Freezing significantly correlated with large changes in odor-evoked periglomerular cell activity, including a robust, generalized facilitation of the response to all odors, broadened odor tuning, and increased neural responses to lower odor concentrations. These generalized effects occurred within 24 h of a single conditioning session, persisted for at least 1 month, and were detectable even in the first moments of the brain’s response to odors. The finding that generalized fear includes altered early sensory processing of not only the threat-predictive stimulus but also novel though categorically-similar stimuli may have important implications for the etiology and treatment of anxiety disorders with sensory sequelae.

Cocaine and Caffeine Effects on the Conditioned Place Preference Test: Concomitant Changes on Early Genes within the Mouse Prefrontal Cortex and Nucleus Accumbens.

Caffeine is the world's most popular psychostimulant and is frequently used as an active adulterant in many illicit drugs including cocaine. Previous studies have shown that caffeine can potentiate the stimulant effects of cocaine and cocaine-induced drug seeking behavior. However, little is known about the effects of this drug combination on reward-related learning, a key process in the maintenance of addiction and vulnerability to relapse. The goal of the present study was thus to determine caffeine and cocaine combined effects on the Conditioned Place Preference (CPP) test and to determine potential differential mRNA expression in the Nucleus Accumbens (NAc) and medial prefrontal cortex (mPFC) of immediate-early genes (IEGs) as well as dopamine and adenosine receptor subunits. Mice were treated with caffeine (5 mg/kg, CAF), cocaine (10 mg/kg, COC), or their combination (caffeine 5 mg/kg + cocaine 10 mg/kg, CAF-COC) and trained in the CPP test or treated with repeated injections inside the home cage. NAc and mPFC tissues were dissected immediately after the CPP test, after a single conditioning session or following psychostimulant injection in the home cage for mRNA expression analysis. CAF-COC induced a marked change of preference to the drug conditioned side of the CPP and a significant increase in locomotion compared to COC. Gene expression analysis after CPP test revealed specific up-regulation in the CAF-COC group of Drd1a, cFos, and FosB in the NAc, and cFos, Egr1, and Npas4 in the mPFC. Importantly, none of these changes were observed when animals received same treatments in their home cage. With a single conditioning session, we found similar effects in both CAF and CAF-COC groups: increased Drd1a and decreased cFos in the NAc, and increased expression of Drd1a and Drd2, in the mPFC. Interestingly, we found that cFos and Npas4 gene expression were increased only in the mPFC of the CAF-COC. Our study provides evidence that caffeine acting as an adulterant could potentiate reward-associated memories elicited by cocaine. This is associated with specific changes in IEGs expression that were observed almost exclusively in mice that received the combination of both psychostimulants in the context of CPP memory encoding and retrieval. Our results highlight the potential relevance of caffeine in the maintenance of cocaine addiction which might be mediated by modifying neural plasticity mechanisms that strengthen learning of the association between drug and environment.

Taste Aversion Learning Despite Long Delays: How Best Explained?

Taste aversion learning (aka conditioned taste aversions or CTA) can occur even when there is delay of some hours between experience of the taste and the subsequent onset of illness. This property of CTA is quite distinct from other forms of associative learning, where typically no association between two events is acquired if they are separated by more than a minute. This paper provides an overview of a series of recent experiments based on the assumption that long-delay CTA is possible only when no potentially overshadowing – or ‘concurrently interfering’ (Revusky, 1971) – events occur during the delay. The general method is one in which in a single conditioning session the rats are first given 8% sucrose, providing the sweet target taste, and 65 min later are injected with lithium chloride. What vary across experiments are the potentially interfering events occurring during the 65-min delay period. When the interfering event is a second, and quite different, taste, namely sour-tasting hydrochloric acid solution (HCl), this produces 1-trial overshadowing of the sucrose aversion, to a degree that is greater when HCl is given late in the delay period, greater when HCl is given in the same context as sucrose and greater when HCl has not been pre-exposed. Other intervening events can also overshadow sucrose aversion learning. These include placement into a novel context, as long as this occurs immediately before injection, and even stimuli that evoke memories of food-related experiences. These results can be accounted for by adding to the Rescorla-Wagner model (Rescorla &amp; Wagner, 1972) the assumption that sickness is comprised of a succession of mini-bouts and the assumption that context-event associations (Wagner, 1981) are important in long-delay CTA.

Incubation of Cocaine Seeking following Brief Cocaine Experience in Mice Is Enhanced by mGluR1 Blockade

The incubation of cocaine craving describes the time-dependent augmentation of cue-induced cocaine seeking during withdrawal from prolonged cocaine self-administration and requires time-dependent changes in neuroplasticity at the level of glutamatergic synapses in the nucleus accumbens (NAc). In contrast to most studies that use multiple cocaine-cue conditioning sessions, the present study tested mice with limited cocaine experience (i.e., a single conditioning session) in the incubation of cue-mediated cocaine seeking and its associated changes in the glutamate system. Mice that self-administered cocaine during a single session exhibited a time-dependent increase in their response for the drug-associated cue as compared to mice that self-administered saline. This behavior was associated with changes in AMPA and NMDA receptor binding characteristics. Furthermore, Group I metabotropic glutamate receptor (mGluR1) mRNA levels were altered in several brain regions, including the NAc. Because of the pivotal role of mGluR1 in the control of cocaine-induced plasticity, we investigated the role of mGluR1 in the formation of drug cue-mediated cocaine seeking. After prolonged withdrawal, mice in which an mGluR1 antagonist was administered following cocaine self-administration displayed increased cocaine seeking compared to vehicle-treated mice. These results suggest that limited cocaine experience is sufficient to induce neurobiological changes that enable an initially neutral cue to acquire motivational value that increases over time, an effect that likely involves glutamate signaling through mGluR1.

Conditioned rewarding effects of morphine and methadone in mice pre-exposed to cocaine

BackgroundMethadone is widely accepted as the most effective treatment of opioid dependence. However, clinical observations indicate that the medication is less effective in individuals abusing cocaine. Diminished therapeutic efficacy of methadone in cocaine users is intriguing, but its mechanism has not been studied. MethodsHere, the conditioned place preference (CPP) procedure was used to examine the effects of the dose, number of conditioning sessions and pre-exposure to cocaine on the rewarding effects of morphine and methadone. Vehicle-pre-exposed and cocainesensitized mice (five injections of 10mg/kg over 16 days) were conditioned using methadone (0, 0.1, 0.5, 3, and 5mg/kg) or morphine (0, 1, and 10mg/kg). Place preference was measured after one and again after two additional conditioning sessions. ResultsAs expected, morphine at 10mg/kg produced CPP following just one conditioning session. While a single conditioning session with 1mg/kg of morphine produced no CPP, the rewarding effect became apparent following two additional conditioning sessions as well as in mice pre-exposed to cocaine. Methadone produced CPP following one conditioning session at doses of 0.5, 3 and 5mg/kg. However, unlike with morphine, methadone's rewarding effect was not enhanced by two additional conditioning sessions or by pre-exposure with cocaine. ConclusionsPrior exposure to cocaine increases unconditioned motivational effects of morphine but not of methadone.

Neither time nor number of context-shock pairings affect long-term dependence of memory on hippocampus

There are still basic uncertainties concerning the role of the hippocampus (HPC) in maintaining long-term context memories. All experiments examining the effects of extensive HPC damage on context memory for a single learning episode find that damage soon after learning results in robust retrograde amnesia. Some experiments find that if the learning-to-damage interval is extended, remote context memories are spared. In contrast, other experiments fail to find spared remote context memory. One possible explanation for inconsistency might be the potency of the context memory conditioning procedure, as the experiments showing spared remote memory used a greater number of context-shock pairings, likely creating a stronger context fear memory. We designed an experiment to directly test the question: does increasing the number of context-shock pairings result in sparing of remote context memory after HPC damage? Six independent groups of rats received either 3 or 12 context-shock pairings during a single conditioning session and then either received extensive HPC damage or Control surgery at 1-week, 2-months, or 4-months after conditioning. 10days after surgery rats were tested for memory of the shock context. Consistent with all relevant studies, HPC damage at the shortest training-surgery interval produced robust retrograde amnesia for both 3- and 12-shock groups whereas the Control rats expressed significantly high levels of memory. At the longer training-surgery interval, HPC damage produced similarly robust retrograde amnesia in the rats in both the 3- and 12-shock groups. These results clearly demonstrate that increasing the number of context-shock pairings within a single learning session does not change the dependence of the memory on the HPC. Current evidence from our group on retrograde amnesia has now shown that partial damage, dorsal vs. ventral damage, discrete cue+context conditioning, time after training, and number of context-shock pairings do not affect HPC dependence of context fear memories. When taken together, the evidence strongly supports a permanent role of the HPC in context memory.

Serial overshadowing of taste aversion learning by stimuli preceding the target taste

Three experiments tested whether events taking place before a rat has access to a target taste, sucrose, can proactively interfere with the acquisition of a sucrose aversion when sucrose is followed by a lithium chloride injection. Using a serial overshadowing procedure with various delays before lithium injection, proactive interference by a taste (Experiments 1 and 3) and by a novel context (Experiment 2) was found following two conditioning sessions, but not after a single conditioning session. Conversely, overshadowing by a taste given after the target was detectable after a single conditioning trial (Experiment 3) and, thus, indicated that retroactive interference involves a process different from that producing proactive interference. A simulation confirmed that the results are consistent with a modified Rescorla and Wagner (1972) interpretation of Revusky's (1971) concurrent interference theory of delay learning.

Social Transmission of Avoidance Behavior under Situational Change in Learned and Unlearned Rats

BackgroundRats receive information from other conspecifics by observation or other types of social interaction. Such social interaction may contribute to the effective adaptation to changes of environment such as situational switching. Learning to avoid dangerous places or objects rapidly occurs with even a single conditioning session, and the conditioned memory tends to be sustained over long periods. The avoidance is important for adaptation, but the details of the conditions under which the social transmission of avoidance is formed are unknown. We demonstrate that the previous experience of avoidance learning is important for the formation of behaviors for social transmission of avoidance and that the experienced rats adapt to a change of situation determined by the presence or absence of aversive stimuli. We systematically investigated social influence on avoidance behavior using a passive avoidance test in a light/dark two-compartment apparatus.Methodology/Principal FindingsRats were divided into two groups, one receiving foot shocks and another with no aversive experience in a dark compartment. Experienced and inexperienced rats were further divided into subjects and partners. In Experiment 1, each subject experienced (1) interaction with an experienced partner, (2) interaction with an inexperienced partner, or (3) no interaction. In Experiment 2, each subject experienced interaction with a partner that received a shock. The entering latency to a light compartment was measured. The avoidance behavior of experienced rats was inhibited by interaction with inexperienced or experienced partners in a safely-changed situation. The avoidance of experienced rats was reinstated in a dangerously-changed situation by interaction with shocked rats. In contrast, the inexperienced rats were not affected by any social circumstances.Conclusions/SignificanceThese results suggest that transmitted information among rats can be updated under a situational change and that the previous experience is crucial for social enhancement and inhibition of avoidance behavior in rats.

Analysis of Ethanol Reinforcement in 1‐Day‐Old Rats: Assessment Through a Brief and Novel Operant Procedure

An accumulating body of experimental evidence supports the notion that, early in development, heterogeneous rats exhibit heightened affinity for ethanol ingestion and are sensitive to the drug's postabsorptive reinforcing effects. The brevity of this ontogenetic period and the limited behavioral repertoire of the newborn represent obstacles in the examination of these phenomena. In the present study, we developed a novel operant technique aimed at examining the neonatal predisposition to gain access to intraoral infusions of different ethanol solutions and other potential reinforcers. In all experiments, 1-day-old rats were placed in a supine position that allowed access to a touch-sensitive sensor. In Paired pups, reinforcers were delivered through an intraoral cannula in a fixed-ratio-1 schedule, based on their physical contact with the sensor. Yoked controls were included to account for overall magnitude of behavioral responding and were given infusions in accord with behavior of the corresponding Paired pup. The reinforcement effect of milk, water and different ethanol solutions (0.75 to 10% v/v) was assessed using a single 15-minute conditioning session. Additional pharmacokinetic studies were conducted to determine blood ethanol concentrations attained during the course of the training session. Within-subjects analysis revealed that Paired pups rapidly learned to increase the probability of behavioral execution to gain access to a biological reinforcer such as milk (Experiment 1). Follow-up experiments indicated that relatively low ethanol concentrations are equally likely to support operant performance (Experiments 2a and 3a). It was also observed that Paired pups exhibited surprisingly high levels of responding during an extinction session, particularly when initially trained with milk or 3% v/v ethanol as reinforcers (Experiment 4). The pharmacokinetic studies indicated that, within a short period of time, ethanol was detectable in blood. Levels attained during conditioning varied as a function of the ethanol concentration utilized as a reinforcer (Experiments 2b and 3b). The present technique appears to represent a valuable tool for examining ethanol self-administration and seeking behavior of the drug during early ontogeny. The results indicate that newborn rats, subjected to the explicit contingency comprising suckling-related behaviors and intraoral ethanol delivery (Paired pups), rapidly learn to gain access to the drug. These results are not explainable through psychomotor effects of ethanol as Yoked pups consumed similar amounts of ethanol and yet exhibited relatively low and consistent levels of responding. The overall pattern of results extends and validates previous observations of substantial affinity for ethanol during early stages of development, a phenomenon rarely encountered in genetically heterogeneous adult rats.

The role of the basolateral amygdala in stimulus–reward memory and extinction memory consolidation and in subsequent conditioned cued reinstatement of cocaine seeking

The consolidation of cue-cocaine associations and extinction learning (i.e. cue-no cocaine associations) into long-term memory probably regulates the long-lasting control of conditioned stimuli (CS) over cocaine-seeking behaviour, and the basolateral amygdala (BLA) may play a role in this phenomenon. To test this hypothesis, rats previously trained to self-administer cocaine underwent a single classical conditioning (CC) session, during which they received passive pairings of cocaine infusions and a novel light + tone stimulus complex. After additional self-administration sessions in the absence of CS presentation and subsequent extinction training sessions, the ability of the CS to reinstate cocaine-seeking on five test days was assessed. Rats received intra-BLA microinfusions of vehicle or the Na+-channel blocker tetrodotoxin (TTX) immediately after CC (consolidation of CS-cocaine associations) or immediately after reinstatement testing (consolidation of extinction learning). TTX administered immediately after CC attenuated subsequent CS-induced reinstatement. In contrast, TTX administered after the first reinstatement test impaired the extinction of cocaine-seeking behaviour during a second reinstatement test by disrupting extinction memory. Overall, these findings suggest that Na+ channel-mediated mechanisms within the BLA mediate the consolidation of both cocaine-stimulus association and extinction learning, two processes that have opposite effects on subsequent cue-induced cocaine-seeking behaviour.

Dopamine D1 or D2 receptor antagonism within the basolateral amygdala differentially alters the acquisition of cocaine-cue associations necessary for cue-induced reinstatement of cocaine-seeking

The basolateral amygdala complex has been implicated in the formation and utilization of cocaine-cue associations in rat models of cue-induced reinstatement to cocaine-seeking behavior. We have previously demonstrated the importance of dopamine inputs to the basolateral amygdala complex in the reinstatement of cocaine-seeking behavior following chronic cocaine self-administration. Here we show that selective blockade of amygdalar dopamine D1 and D2 receptors during acquisition of cocaine-cue associations has distinctive effects on subsequent conditioned-cued cocaine-seeking behavior. Male, Sprague–Dawley rats were first trained to self-administer i.v. cocaine on a fixed ratio 1 schedule for 5 days. Subjects then received bilateral, intra-basolateral amygdala complex infusions of a dopamine D1 receptor antagonist (SCH23390, 0.25–2.0μg/side; experiment 1), a dopamine D2 receptor antagonist (raclopride, 0.625–5.0μg/side; experiment 2), or vehicle just prior to a single classical conditioning session, during which a light+tone cue was discretely paired with passive infusions of cocaine in the absence of lever responding. Following five additional days of cocaine self-administration and 7–10 days of extinction training, animals underwent multiple tests for cue-induced reinstatement. SCH23390 (2.0μg/side), administered at the time of cocaine-cue association only, produced an attenuation of reinstatement to cue-induced cocaine-seeking behavior. In contrast, low doses of raclopride potentiated, while a higher dose of raclopride attenuated cue-induced reinstatement. These results demonstrate unique contributions of D1 vs. D2 receptors in mediating dopamine inputs within the basolateral amygdala complex during the formation of cocaine-stimulus associations that are critical for cue-induced reinstatement.

Single Neurons in CA1 Hippocampus Encode Trace Interval Duration during Trace Heart Rate (Fear) Conditioning in Rabbit

This study sought to determine whether CA1 hippocampal neurons encode the duration of the trace interval during trace fear conditioning. Single neurons were recorded extracellularly in the CA1 of rabbits during and after a single trace fear classical conditioning session. Trace fear conditioning trials consisted of an auditory conditioned stimulus (CS; 3 sec) and a fear-producing shock unconditioned stimulus (US; 0.5 sec) separated by a silent trace interval. One group of rabbits was trained using a 10 sec trace interval (n = 5), and another group was trained using a 20 sec trace interval (n = 4). These groups were compared with pseudoconditioning control rabbits (n = 5 and n = 4, respectively) that received unpaired CSs and USs. One day after trace and pseudo fear conditioning rabbits received a CS-alone retention session in which no USs were presented. The trace conditioned groups showed larger bradycardiac-fear responses on CS-alone trials compared with the pseudoconditioning groups. A significant percentage of CA1 neurons from the 10 and 20 sec trace groups (24 and 28%, respectively) showed maximal firing on CS-alone retention trials timed to 10 sec (+/-1.5 sec) and 20 sec (+/-2.0 sec) after CS offset, respectively. These latencies were similar to the duration of the trace interval used on previous CS-trace-US trials. Timed CA1 firing was not seen in pseudoconditioning control animals, suggesting that a subset of CA1 neurons encoded the trace interval duration. The percentage of neurons encoding trace duration was largest when rabbits exhibited significant fear responses to the CS, suggesting that trace encoding was related to the strength of the CS and US association.

The development of olfactory conditioned ejaculatory preferences in the male rat: II. Parametric manipulation of conditioning session number and duration

We have previously demonstrated that repeated pairing of a neutral odor with copulation produces a subsequent conditioned ejaculatory preference (CEP) for females bearing that odor. The present study examines the course of CEP development. In Experiment 1, Long–Evans male rats were allowed access to almond-scented, sexually receptive females for either one, five, or nine conditioning sessions that were 30 min in duration. Males given five or nine sessions displayed significant CEPs. In Experiment 2, male rats were given a single conditioning session with multiple almond-scented females until either a duration (60, 120, 180, or 240 min) or copulatory criterion (two, four, or six ejaculatory series) was satisfied. Males that received 120-, 180-, or 240-min sessions or four ejaculations displayed significant CEPs; males that received two or six ejaculations displayed a trend for CEPs. Analysis of effect size estimates revealed that the strongest CEPs were produced by 120 min of copulation or four ejaculations. In Experiment 3, males receiving nine conditioning sessions each 30 min in duration displayed a more enduring CEP than did males receiving a single conditioning session 240 min in duration. These data suggest that early sexual experiences have particularly powerful influences on subsequent sexual preferences and that the development of sexual preferences are influenced by interactions between CS–UCS pairings and motivational variables.

Neurotoxic lesions of the dorsal hippocampus disrupt auditory-cued trace heart rate (fear) conditioning in rabbits.

The first experiment in this study used the classical heart rate (HR) conditioning paradigm to determine if rabbits could associate an auditory conditioned stimulus (CS) and a fear-producing shock-unconditioned stimulus (US) separated by an empty 10-s trace interval. Trace conditioned rabbits (n = 7) acquired significant bradycardiac conditioned HR responses on CS-alone test trials during a single 35-trial conditioning session. Control animals (n = 7) which received unpaired CSs and USs did not show HR conditioning. During a retention session of CS-alone trials 24 h after the conditioning session, some trace-conditioned animals showed conditioned HR responses immediately following CS onset (n = 3), while others showed responses appropriately timed to the US onset (n = 4) used in trace conditioning 24 h earlier. Thus, rabbits remember the duration of the long 10-s trace interval 24 h after a single day of training. The second part of this study sought to determine if cells in the dorsal hippocampus play a role in trace HR conditioning. Rabbits were given bilateral ibotenic acid lesions in the neocortex (n = 7) or dorsal hippocampus (n = 8). During trace conditioning and retention, neocortical animals showed conditioned HR responses to the CS, whereas the hippocampal group showed no significant HR conditioning. One week after trace conditioning, the same animals received a delay HR conditioning session where no trace interval separated the CS and US. During delay conditioning, hippocampal animals showed significant conditioned HR responses to the CS that were similar to the neocortical group. Thus, the dorsal hippocampus plays a critical role in rabbit HR conditioning when the CS and US are separated by a 10-s trace interval. This paradigm may be ideal for in vivo electrophysiological recording studies because rabbits are easily immobilized during the testing procedure, and learning occurs during a single day of training.

Effects of lesions to the hippocampus on contextual fear: Evidence for a disruption of freezing and avoidance behavior but not context conditioning.

The effects of ibotenic lesions of the hippocampus on conditioning to contextual cues during classical fear conditioning in rats were evaluated by (a) the amount of freezing elicited by contextual cues and (b) the relative avoidance of a shock compartment. In Experiment 1, lesions to the hippocampus had no effect on contextual freezing and marginally affected avoidance after repeated sessions. Experiment 2 showed that lesions to the hippocampus disrupted avoidance when tested after a single conditioning session, while leaving unaffected the acquisition of contextual freezing. Experiment 3 indicated that these lesions decreased the acquisition of contextual freezing when higher footshock intensity was used but had no effect on avoidance after repeated conditioning sessions. These results show that freezing and avoidance do not quantify context conditioning similarly. They further indicate that lesions to the hippocampus may disrupt the expression of these behaviors used as measures of context conditioning but not the acquisition of context conditioning per se.

Effects of lesions to the hippocampus on contextual fear: evidence for a disruption of freezing and avoidance behavior but not context conditioning.

The effects of ibotenic lesions of the hippocampus on conditioning to contextual cues during classical fear conditioning in rats were evaluated by (a) the amount of freezing elicited by contextual cues and (b) the relative avoidance of a shock compartment. In Experiment 1, lesions to the hippocampus had no effect on contextual freezing and marginally affected avoidance after repeated sessions. Experiment 2 showed that lesions to the hippocampus disrupted avoidance when tested after a single conditioning session, while leaving unaffected the acquisition of contextual freezing. Experiment 3 indicated that these lesions decreased the acquisition of contextual freezing when higher footshock intensity was used but had no effect on avoidance after repeated conditioning sessions. These results show that freezing and avoidance do not quantify context conditioning similarly. They further indicate that lesions to the hippocampus may disrupt the expression of these behaviors used as measures of context conditioning but not the acquisition of context conditioning per se.