Onset Of Conditioned Stimulus Research Articles

Disruption of positive- and negative-feature morphine interoceptive occasion setters by dopamine receptor agonism and antagonism in male and female rats.

Internally perceived stimuli evoked by morphine administration can form Pavlovian associations such that they can function as occasion setters (OSs) for externally perceived reward cues in rats, coming to modulate reward-seeking behaviour. Though much research has investigated mechanisms underlying opioid-related reinforcement and analgesia, neurotransmitter systems involved in the functioning of opioids as Pavlovian interoceptive discriminative stimuli remain to be disentangled despite documented differences in the development of tolerance to analgesic versus discriminative stimulus effects. Dopamine has been implicated in many opioid-related behaviours, so we aimed to investigate the role of this neurotransmitter in expression of morphine occasion setting. Male and female rats were assigned to positive- (FP) or negative-feature (FN) groups and received an injection of morphine or saline before each training session. A 15-s white noise conditioned stimulus (CS) was presented 8 times during every training session; offset of this stimulus was followed by 4-s access to liquid sucrose on morphine, but not saline, sessions for FP rats. FN rats learned the reverse contingency. Following stable discrimination, rats began generalization testing for expression of morphine-guided sucrose seeking after systemic pretreatment with different doses of the non-selective dopamine receptor antagonist, flupenthixol, and the non-selective dopamine receptor agonist, apomorphine, combined with training doses of morphine or saline in a Latin-square design. The morphine discrimination was acquired under both FP and FN contingencies by males and females. Neither flupenthixol nor apomorphine at any dose substituted for morphine, but both apomorphine and flupenthixol disrupted expression of the morphine OS. This inhibition was specific to sucrose seeking during CS presentations rather than during the period before CS onset and, in the case of apomorphine more so than flupenthixol, to trials on which access to sucrose was anticipated. Our findings lend support to a mechanism of occasion setting involving gating of CS-induced dopamine release rather than by direct dopaminergic modulation by the morphine stimulus.

Divergent encoding of active avoidance behavior in corticostriatal and corticolimbic projections

Active avoidance behavior, in which an animal performs an action to avoid a stressor, is crucial for survival and may provide insight into avoidance behaviors seen in anxiety disorders. Active avoidance requires the dorsomedial prefrontal cortex (dmPFC), which is thought to regulate avoidance via downstream projections to the striatum and amygdala. However, the endogenous activity of dmPFC projections during active avoidance learning has never been recorded. Here we utilized fiber photometry to record from the dmPFC and its axonal projections to the dorsomedial striatum (DMS) and the basolateral amygdala (BLA) during active avoidance learning in both male and female mice. We examined neural activity during conditioned stimulus (CS) presentations and during clinically relevant behaviors such as active avoidance or cued freezing. Both prefrontal projections showed learning-related increases in activity during CS onset throughout active avoidance training. The dmPFC as a whole showed increased and decreased patterns of activity during avoidance and cued freezing, respectively. Finally, dmPFC-DMS and dmPFC-BLA projections show divergent encoding of active avoidance behavior, with the dmPFC-DMS projection showing increased activity and the dmPFC-BLA projection showing decreased activity during active avoidance. Our results demonstrate task-relevant encoding of active avoidance in projection-specific dmPFC subpopulations that play distinct but complementary roles in active avoidance learning.

Hippocampal theta phase–contingent memory retrieval in delay and trace eyeblink conditioning

Hippocampal theta oscillations (3–12Hz) play a prominent role in learning. It has been suggested that encoding and retrieval of memories are supported by different phases of the theta cycle. Our previous study on trace eyeblink conditioning in rabbits suggests that the timing of the conditioned stimulus (CS) in relation to theta phase affects encoding but not retrieval of the memory trace. Here, we directly tested the effects of hippocampal theta phase on memory retrieval in two experiments conducted on adult female New Zealand White rabbits. In Experiment 1, animals were trained in trace eyeblink conditioning followed by extinction, and memory retrieval was tested by presenting the CS at troughs and peaks of the theta cycle during different stages of learning. In Experiment 2, animals were trained in delay conditioning either contingent on a high level of theta or at a random neural state. Conditioning was then followed by extinction conducted either at a random state, contingent on theta trough or contingent on theta peak. Our current results indicate that the phase of theta at CS onset has no effect on the performance of the behavioral learned response at any stage of classical eyeblink conditioning or extinction. In addition, theta-contingent trial presentation does not improve learning during delay eyeblink conditioning. The results are consistent with our earlier findings and suggest that the theta phase alone is not sufficient to affect learning at the behavioral level. It seems that the retrieval of recently acquired memories and consequently performing a learned response is moderated by neural mechanisms other than hippocampal theta.

Distinct state anxiety after predictable and unpredictable fear training in mice

Sustained fear paradigms in rodents have been developed to monitor states of anxious apprehension and to model situations in patients suffering from long-lasting anxiety disorders. A recent report describes a fear conditioning paradigm, allowing distinction between phasic and sustained states of conditioned fear in non-restrained mice. However, so far no prospective studies have yet been conducted to elucidate whether induction of phasic or sustained fear can affect states of anxiety. Here, we used CS (conditioned stimulus) and US (unconditioned stimulus) pairing with predictable and unpredictable timing to induce phasic and sustained fear in mice. State anxiety during various fear response components was assessed using the elevated plus-maze test. Training with unpredictable CS-US timing resulted in CS-evoked sustained components of fear (freezing), while predictable CS-US timing resulted in rapid decline. Data suggested the influence of training procedure on state anxiety which is dependent on progression of conditioned fear during fear memory retrieval. Animals trained with unpredictable CS-US timing showed an unchanged high anxiety state throughout behavioral observation. In contrast, mice trained with predictable CS-US timing showed anxiolytic-like behavior 3min after CS onset, which was accompanied by a fast decline of the fear conditioned response (freezing). Further systematic studies are needed to validate the phasic/sustained fear model in rodents as translational model for anxiety disorders in humans.

Individual trial analysis evidences clock and non-clock based conditioned suppression behaviors in rats

We analyzed the temporal pattern of conditioned suppression of lever-pressing for food in rats conditioned with tone-shock pairings using either a 10 or 15s conditioned stimulus (CS)-unconditioned stimulus (US) interval with a CS duration that was three times the CS-US interval. The analysis of average suppression and of individual trials was performed during Probe CS-alone trials and when a short gap was inserted during the CS. The pattern of suppression followed the classical temporal rules: (1) scalar property, (2) a shift in peak suppression due to a gap, compatible with a Stop rule, (3) a three-state pattern of lever-pressing in individual trials, with abrupt start and stop of suppression. The peak of the average suppression curve, but not the middle time, was anticipatory to the programmed US time. The pattern of lever-pressing in individual trials unraveled two types of start of suppression behavior: a clock-based biphasic responding, with a burst of lever-pressing before suppression, and a non-clock based monophasic reduction of lever-pressing close to the CS onset. The non-clock based type of behavior may be responsible for the anticipatory peak time, and the biphasic pattern of lever-pressing may reflect the decision stage described in clock models.

Implicit Memory in Monkeys: Development of a Delay Eyeblink Conditioning System with Parallel Electromyographic and High-Speed Video Measurements.

Delay eyeblink conditioning, a cerebellum-dependent learning paradigm, has been applied to various mammalian species but not yet to monkeys. We therefore developed an accurate measuring system that we believe is the first system suitable for delay eyeblink conditioning in a monkey species (Macaca mulatta). Monkey eyeblinking was simultaneously monitored by orbicularis oculi electromyographic (OO-EMG) measurements and a high-speed camera-based tracking system built around a 1-kHz CMOS image sensor. A 1-kHz tone was the conditioned stimulus (CS), while an air puff (0.02 MPa) was the unconditioned stimulus. EMG analysis showed that the monkeys exhibited a conditioned response (CR) incidence of more than 60% of trials during the 5-day acquisition phase and an extinguished CR during the 2-day extinction phase. The camera system yielded similar results. Hence, we conclude that both methods are effective in evaluating monkey eyeblink conditioning. This system incorporating two different measuring principles enabled us to elucidate the relationship between the actual presence of eyelid closure and OO-EMG activity. An interesting finding permitted by the new system was that the monkeys frequently exhibited obvious CRs even when they produced visible facial signs of drowsiness or microsleep. Indeed, the probability of observing a CR in a given trial was not influenced by whether the monkeys closed their eyelids just before CS onset, suggesting that this memory could be expressed independently of wakefulness. This work presents a novel system for cognitive assessment in monkeys that will be useful for elucidating the neural mechanisms of implicit learning in nonhuman primates.

Phase matters: responding to and learning about peripheral stimuli depends on hippocampal θ phase at stimulus onset.

Hippocampal θ (3–12 Hz) oscillations are implicated in learning and memory, but their functional role remains unclear. We studied the effect of the phase of local θ oscillation on hippocampal responses to a neutral conditioned stimulus (CS) and subsequent learning of classical trace eyeblink conditioning in adult rabbits. High-amplitude, regular hippocampal θ-band responses (that predict good learning) were elicited by the CS when it was timed to commence at the fissure θ trough (Trough group). Regardless, learning in this group was not enhanced compared with a yoked control group, possibly due to a ceiling effect. However, when the CS was consistently presented to the peak of θ (Peak group), hippocampal θ-band responding was less organized and learning was retarded. In well-trained animals, the hippocampal θ phase at CS onset no longer affected performance of the learned response, suggesting a time-limited role for hippocampal processing in learning. To our knowledge, this is the first study to demonstrate that timing a peripheral stimulus to a specific phase of the hippocampal θ cycle produces robust effects on the synchronization of neural responses and affects learning at the behavioral level. Our results support the notion that the phase of spontaneous hippocampal θ oscillation is a means of regulating the processing of information in the brain to a behaviorally relevant degree.

Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS.

Classical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex. The aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS. A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality. CR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset. Acquisition and timing of conditioned eyeblink responses is modified by cerebellar tDCS in a polarity dependent manner.

Impaired trace fear conditioning and diminished ERK1/2 phosphorylation in the dorsal hippocampus of adult rats administered alcohol as neonates.

Utilizing a rat model of fetal alcohol spectrum disorder (FASD), ethanol was administered over postnatal days (PD) 4 to 9. As adults, control and ethanol rats underwent trace fear conditioning (TFC), in which a tone conditioned stimulus (CS) and footshock unconditioned stimulus (US) were repeatedly paired, though the two stimuli never overlapped in time. Following training in Experiment 1, conditioned fear (freezing) to the tone CS was dose-dependently reduced in ethanol rats relative to controls. Experiment 2 was designed to test whether the TFC deficit varied based on the duration of the trace interval (TI; time from CS offset to US onset). Holding the time separating CS onset from US onset constant at 20 sec, control and ethanol rats were trained with a 5 or 15 sec tone CS, followed 15 or 5 sec later, respectively, by the US. Conditioned fear to the tone CS was significantly reduced in high dose ethanol rats trained with the 15 sec TI only. Acquisition and consolidation of trace fear memories relies on forebrain N-methyl-d-aspartate receptor (NMDAR) signaling, including the downstream phosphorylation of extracellular signal-regulated kinase 1/2 (pERK1/2). Separate rats were trained with the 5 or 15 sec TI and then sacrificed 1 hr later. Significant reductions in pERK1/2-positive neurons were seen in areas CA1 and CA3 of the dorsal hippocampus (DH) following training at both TIs in ethanol rats. The disruption of DH learning-dependent plasticity appears tied to freezing behavior in ethanol rats, but only when the training stimuli are separated by more than 5 sec.

Conditioning and time representation in long short-term memory networks

Dopaminergic models based on the temporal-difference learning algorithm usually do not differentiate trace from delay conditioning. Instead, they use a fixed temporal representation of elapsed time since conditioned stimulus onset. Recently, a new model was proposed in which timing is learned within a long short-term memory (LSTM) artificial neural network representing the cerebral cortex (Rivest et al. in J Comput Neurosci 28(1):107-130, 2010). In this paper, that model's ability to reproduce and explain relevant data, as well as its ability to make interesting new predictions, are evaluated. The model reveals a strikingly different temporal representation between trace and delay conditioning since trace conditioning requires working memory to remember the past conditioned stimulus while delay conditioning does not. On the other hand, the model predicts no important difference in DA responses between those two conditions when trained on one conditioning paradigm and tested on the other. The model predicts that in trace conditioning, animal timing starts with the conditioned stimulus offset as opposed to its onset. In classical conditioning, it predicts that if the conditioned stimulus does not disappear after the reward, the animal may expect a second reward. Finally, the last simulation reveals that the buildup of activity of some units in the networks can adapt to new delays by adjusting their rate of integration. Most importantly, the paper shows that it is possible, with the proposed architecture, to acquire discharge patterns similar to those observed in dopaminergic neurons and in the cerebral cortex on those tasks simply by minimizing a predictive cost function.

Learning and memory in the Port Jackson shark, Heterodontus portusjacksoni

Basic understanding of the fundamental principles and mechanisms involved in learning is lacking for elasmobranch fishes. Our aim in this study was to experimentally investigate the learning and memory capacity of juvenile Port Jackson sharks, Heterodontus portusjacksoni. Sharks (N=30) were conditioned over a 19-day period to associate an underwater LED light or stream of air-bubbles [conditioned stimulus (CS)] with a food reward [unconditioned stimulus (US)], using three procedures (delay, trace and control). During experiments, the CS signalled at a random time between 180 and 300s for 30s (six times per day). For the delay the US overlapped in time with the CS, for the trace the US delivered 10s after the CS and for our control the US was delivered at random time between 180 and 300s after the CS. H. portusjacksoni sharks trained in all procedures improved consistently in their time to obtain food, indicative of Pavlovian learning. Importantly, the number of sharks in the feeding area 5s prior to CS onset did not change over time for any procedures. However, significantly more sharks were present 5safter CS onset for delay for both air-bubble and light CS. Sharks trained in the delay and trace procedures using air-bubbles as the CS also displayed significantly more anticipatory behaviours, such as turning towards the CS and biting. Sharks trained with the light CS did not exhibit such behaviours; however, trace procedural sharks did show a significant improvement in moving towards the CS at its onset. At 20 and 40days after the end of the conditioning experiments, some sharks were presented the CS without reward. Two sharks trained in the delay procedure using air-bubbles as the CS exhibited biting behaviours: one at 20 and the other at 40days. This study demonstrates that H. portusjacksoni have the capacity to learn a classical conditioning procedure relatively quickly (30 trials during 5days) and associate two time-separated events and retention of learnt associations for at least 24h and possibly up to 40days.

Towards a unified model of pavlovian conditioning: short review of trace conditioning models.

There are three basic paradigms of classical conditioning: delay, trace and context conditioning where presentation of a conditioned stimulus (CS) or a context typically predicts an unconditioned stimulus (US). In delay conditioning CS and US normally coterminate, whereas in trace conditioning an interval of time exists between CS termination and US onset. The modeling of trace conditioning is a rather difficult computational problem and is a challenge to the behavior and connectionist approaches mainly due to a time gap between CS and US. To account for trace conditioning, Pavlov (Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex, Oxford University Press, London, 1927) postulated the existence of a stimulus "trace" in the nervous system. Meanwhile, there exist many other options for solving this association problem. There are several excellent reviews of computational models of classical conditioning but none has thus far been devoted to trace conditioning. Eight representative models of trace conditioning aimed at building a prospective model are being reviewed below in a brief form. As a result, one of them, comprising the most important features of its predecessors, can be suggested as a real candidate for a unified model of trace conditioning.

In the Blink of an Eye: Investigating the Role of Awarenessin Fear Responding by Measuring the Latency ofStartle Potentiation.

The latency of startle reflex potentiation may shed light on the aware and unaware processes underlying associative learning, especially associative fear learning. We review research suggesting that single-cue delay classical conditioning is independent of awareness of the contingency between the conditioned stimulus (CS) and the unconditioned stimulus (US). Moreover, we discuss research that argues that conditioning independent of awareness has not been proven. Subsequently, three studies from our lab are presented that have investigated the role of awareness in classical conditioning, by measuring the minimum latency from CS onset to observed changes in reflexive behavior. In sum, research using this method shows that startle is potentiated 30 to 100 ms after CS onset following delay conditioning. Following trace fear conditioning, startle is potentiated 1500 ms after CS presentation. These results indicate that the process underlying delay conditioned responding is independent of awareness, and that trace fear conditioned responding is dependent on awareness. Finally, this method of investigating the role of awareness is discussed and future research possibilities are proposed.

How Fast is Fear?

The minimum latency of potentiated startle after delay and trace fear conditioning was investigated. Delay conditioning is hypothesized to be mediated by automatic processes, whereas trace conditioning is hypothesized to involve controlled cognitive processes. In a group receiving delay conditioning, a tone conditioned stimulus (CS) signaled an electric shock unconditioned stimulus (US) presented 1,000 ms after CS onset. In a group receiving trace conditioning, a 200 ms tone CS was followed by an 800 ms gap prior to US presentation. Two control groups received unpaired CS/US presentations. It was hypothesized that fear-potentiated startle should be observed at shorter time intervals after CS onset in the group receiving delay conditioning compared to the group receiving trace conditioning. The results showed increased startle at 100 and 150 ms after CS onset in the group receiving delay conditioning compared to the unpaired group. In the group receiving trace conditioning, increased startle was observed at 1,500 ms after CS onset compared to the unpaired group. This supports the idea that conditioned fear after delay conditioning may be due to automatic processes, whereas trace conditioning is dependent on controlled processes.

Effects of a marihuana homologue (Pyrahexyl) on avoidance learning in the gerbil.

Pyrahexyl (synhexyl, 3-hexy1-7,8,9,10-tetrahydro-6,6,9-trimethy1-6H-dibenzo[b,d] pyran-l-ol) is a synthetic cannabis compound having behavioural effects similar to tetrahydrocannabinol (mc) one of the active principles of Cannabis sativa L (Hollister, Richards & Gillespie, 1968). Although pyrahexyl has been studied in man (Stockings, 1947; Parker & Wrigley, 1950; Thompson & Procter, 1953; Hollister & others, 1968), little is known of its specific behavioural effects except that it seems to have euphoriant properties. Recently, Abel (1969) found in rats that pyrahexyl markedly reduced the amount of time required to resume lever pressing for water after this activity had been suppressed by a fear-producing stimulus and Abel & Schiff (1969) reported that pyrahexyl increased curiosity in rats as measured by the time they spent observing other animals. We now report its effect in an avoidance learning situation. The particular testing procedure chosen assessed the effect of pyrahexyl on the acquisition of new behaviour rather than its effect upon a previously learned response as examined by Abel (1969). Six adult male Mongolian gerbils (Meriones Unguiculatus), 80-90 g, were injected intraperitoneally with 0.2 ml of a solution of pyrahexyl (2.3 mg/kg) in olive oil ; six control animals received only oil injections. After 2 h animals were placed individually into a standard two-compartment automated shuttle box (Lehigh Valley Electronics, Model 146-04) in which they could avoid being shocked through the grid floor by jumping over a barrier dividing the apparatus. An auditory signal was the conditioned stimulus and a 0.8 mA constant current electric shock the unconditioned stimulus. The conditioned stimulus preceded the onset of shock by 5 s. If an avoidance response was not made during this period, shock came on and remained on until the animal jumped over the barrier. Each presentation of the conditioned stimulus and the performance of a jumping response constituted a single trial ; 50 such trials were given each day with a 25 s interval between trials. A total of 250 trials was given over a 5-day test period. The test apparatus and recording equipment were completely automated and the animals were not disturbed once the daily test period had begun. Records were kept of the number of successful trials; the time taken to jump the barrier after each conditioned stimulus onset (jump latency); and the number of between trial jumps which were not associated with the conditioned stimulus. As shown in Fig. IA, pyrahexyl-injected animals made more avoidance responses on the first day of testing than did control animals ; this difference was statistically significant (t-test, Edwards, 1964; t = 1.89, P<0.05). By the second test day all animals had achieved high performance levels and no differences in acquisition of the avoidance response were found between groups on this or any subsequent day. However, analysis of variance (Edwards, 1964) showed that, compared to controls pyrahexyl-injected animals had significantly lower response latencies to the conditioned stimulus throughout the five day test period (F = 11, 21, df, 1, 10, P<0.01, see Fig. 1B). There was no effect of the drug on responding independent of presentation of the conditioned stimulus (between-trial jumps). The mean daily between-trial jump rates were : pyrahexyl animals, 5C = 12.19, range 2.8-47; control animals, X = 14.32, range 4-0-50.

Revealing Context-Specific Conditioned Fear Memories with Full Immersion Virtual Reality

The extinction of conditioned fear is known to be context-specific and is often considered more contextually bound than the fear memory itself (Bouton, 2004). Yet, recent findings in rodents have challenged the notion that contextual fear retention is initially generalized. The context-specificity of a cued fear memory to the learning context has not been addressed in the human literature largely due to limitations in methodology. Here we adapt a novel technology to test the context-specificity of cued fear conditioning using full immersion 3-D virtual reality (VR). During acquisition training, healthy participants navigated through virtual environments containing dynamic snake and spider conditioned stimuli (CSs), one of which was paired with electrical wrist stimulation. During a 24-h delayed retention test, one group returned to the same context as acquisition training whereas another group experienced the CSs in a novel context. Unconditioned stimulus expectancy ratings were assayed on-line during fear acquisition as an index of contingency awareness. Skin conductance responses time-locked to CS onset were the dependent measure of cued fear, and skin conductance levels during the interstimulus interval were an index of context fear. Findings indicate that early in acquisition training, participants express contingency awareness as well as differential contextual fear, whereas differential cued fear emerged later in acquisition. During the retention test, differential cued fear retention was enhanced in the group who returned to the same context as acquisition training relative to the context shift group. The results extend recent rodent work to illustrate differences in cued and context fear acquisition and the contextual specificity of recent fear memories. Findings support the use of full immersion VR as a novel tool in cognitive neuroscience to bridge rodent models of contextual phenomena underlying human clinical disorders.

A method to study global spatial patterns related to sensory perception in scalp EEG

Prior studies of multichannel ECoG from animals showed that beta and gamma oscillations carried perceptual information in both local and global spatial patterns of amplitude modulation, when the subjects were trained to discriminate conditioned stimuli (CS). Here the hypothesis was tested that similar patterns could be found in the scalp EEG human subjects trained to discriminate simultaneous visual-auditory CS. Signals were continuously recorded from 64 equispaced scalp electrodes and band-pass filtered. The Hilbert transform gave the analytic phase, which segmented the EEG into temporal frames, and the analytic amplitude, which expressed the pattern in each frame as a feature vector. Methods applied to the ECoG were adapted to the EEG for systematic search of the beta–gamma spectrum, the time period after CS onset, and the scalp surface to locate patterns that could be classified with respect to type of CS. Spatial patterns of EEG amplitude modulation were found from all subjects that could be classified with respect to stimulus combination type significantly above chance levels. The patterns were found in the beta range (15–22 Hz) but not in the gamma range. They occurred in three short bursts following CS onset. They were non-local, occupying the entire array. Our results suggest that the scalp EEG can yield information about the timing of episodically synchronized brain activity in higher cognitive function, so that future studies in brain–computer interfacing can be better focused. Our methods may be most valuable for analyzing data from dense arrays with very high spatial and temporal sampling rates.

Interstimulus interval and delivery cues influence timed conditioned responding in rats

Appetitive contextual excitation supported by intertrial unconditioned stimuli was more easily overcome by timed conditioned responding in rats using quiet (Experiment 1) rather than noisy (Experiment 2) food pellet deliveries. Head-entry responding in acquisition peaked above the contextual baseline when pellet delivery occurred 10, 30, 60, or 90 s after the onset of the 120-s white-noise conditioned stimulus (CS). Special tests in extinction revealed CS onset and offset were conditioned by pellet delivery at 0 and 120 s, respectively. Responding was not undermined in Experiment 3 when noisy pellet deliveries replaced quiet pellet deliveries. Our results suggest that micro-stimuli occasioned at different times during the CS are vulnerable to overshadowing, but do not lose strength if they are already predictive.

Fear potentiated startle at short intervals following conditioned stimulus onset during delay but not trace conditioning

The latency of conditioned fear after delay and trace conditioning was investigated. Some argue that delay conditioning is not dependent on awareness. In contrast, trace conditioning, where there is a gap between the conditioned stimulus (CS) and the unconditioned stimulus (US), is assumed to be dependent on awareness. In the present study, a tone CS signaled a noise US presented 1000 ms after CS onset in the delay conditioning group. In the trace conditioning group, a 200-ms tone CS was followed by an 800-ms gap prior to US presentation. Fear-potentiated startle should be seen at shorter intervals after delay conditioning compared to trace conditioning. Analyses showed increased startle at 30, 50, 100, and 150 ms after CS onset following delay conditioning compared to trace conditioning. This implies that fear-relevant stimuli elicit physiological reactions before extended processing of the stimuli occur, following delay, but not trace conditioning.

Computational Models of Timing Mechanisms in the Cerebellar Granular Layer

A long-standing question in neuroscience is how the brain controls movement that requires precisely timed muscle activations. Studies using Pavlovian delay eyeblink conditioning provide good insight into this question. In delay eyeblink conditioning, which is believed to involve the cerebellum, a subject learns an interstimulus interval (ISI) between the onsets of a conditioned stimulus (CS) such as a tone and an unconditioned stimulus such as an airpuff to the eye. After a conditioning phase, the subject’s eyes automatically close or blink when the ISI time has passed after CS onset. This timing information is thought to be represented in some way in the cerebellum. Several computational models of the cerebellum have been proposed to explain the mechanisms of time representation, and they commonly point to the granular layer network. This article will review these computational models and discuss the possible computational power of the cerebellum.