Pavlovian Eyeblink Conditioning Research Articles

Discrimination training affects stimulus generalization in mice during Pavlovian eyeblink conditioning.

The delicate balance between discrimination and generalization of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investigate generalization of cerebellar-related eyelid motor responses, we find generalization effects on amount, amplitude and timing of the conditioned responses. However, it is unknown what the generalization effects are following differential training. We trained mice to close their eyelids to a 10 kHz tone with an air-puff as the reinforcing stimulus (CS+), while alternatingly exposing them to a tone frequency of either 4 kHz, 9 kHz or 9.5 kHz without the air-puff (CS-) during the training blocks. We tested the generalization effects during the expression of the responses after the training period with tones ranging from 2 kHz to 20 kHz. Our results show that the level of generalization tended to positively correlate with the difference between the CS+ and the CS- training stimuli. These effects of generalization were found for the probability, amplitude but not for the timing of the conditioned eyelid responses. These data indicate the specificity of the generalization effects following differential versus non-differential training, highlighting the relevance of discrimination learning for stimulus generalization.

Cerebellum-dependent associative learning is not impaired in a mouse model of neurofibromatosis type 1

Individuals with Neurofibromatosis type 1 (NF1) experience a high degree of motor problems. The cerebellum plays a pivotal role in motor functioning and the NF1 gene is highly expressed in cerebellar Purkinje cells. However, it is not well understood to what extent NF1 affects cerebellar functioning and how this relates to NF1 motor functioning. Therefore, we subjected global Nf1+/− mice to a cerebellum-dependent associative learning task, called Pavlovian eyeblink conditioning. Additionally, we assessed general motor function and muscle strength in Nf1+/− mice. To our surprise, we found that Nf1+/− mice showed a moderately increased learning rate of conditioned eyeblink responses, as well as improved accuracy in the adaptive timing of the eyeblink responses. Locomotion, balance, general motor function, and muscle strength were not affected in Nf1+/− mice. Together, our results support the view that cerebellar function in Nf1+/− mice is unimpaired.

Stimulus Generalization in Mice during Pavlovian Eyeblink Conditioning.

Here, we investigate stimulus generalization in a cerebellar learning paradigm, called eyeblink conditioning. Mice were conditioned to close their eyes in response to a 10-kHz tone by repeatedly pairing this tone with an air puff to the eye 250 ms after tone onset. After 10 consecutive days of training, when mice showed reliable conditioned eyelid responses to the 10-kHz tone, we started to expose them to tones with other frequencies, ranging from 2 to 20 kHz. We found that mice had a strong generalization gradient, whereby the probability and amplitude of conditioned eyelid responses gradually decreases depending on the dissimilarity with the 10-kHz tone. Tones with frequencies closest to 10 kHz evoked the most and largest conditioned eyelid responses and each step away from the 10-kHz tone resulted in fewer and smaller conditioned responses (CRs). In addition, we found that tones with lower frequencies resulted in CRs that peaked earlier after tone onset compared with those to tones with higher frequencies. Together, our data show prominent generalization patterns in cerebellar learning. Since the known function of cerebellum is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even addiction, our data imply generalization controlled by cerebellum in all these domains.

Influence of various temporal recoding on pavlovian eyeblink conditioning in the cerebellum

We consider the Pavlovian eyeblink conditioning (EBC) via repeated presentation of paired conditioned stimulus (tone) and unconditioned stimulus (US; airpuff). In an effective cerebellar ring network, we change the connection probability from Golgi to granule (GR) cells, and make a dynamical classification of various firing patterns of the GR cells. Individual GR cells are thus found to show various well- and ill-matched firing patterns relative to the US timing signal. Then, these variously-recoded signals are fed into the Purkinje cells (PCs) through the parallel-fibers (PFs). Based on such unique dynamical classification of various firing patterns, we make intensive investigations on the influence of various temporal recoding (i.e., firing patterns) of the GR cells on the synaptic plasticity of the PF-PC synapses and the subsequent learning process for the EBC. We first note that the variously-recoded PF signals are effectively depressed by the (error-teaching) instructor climbing-fiber (CF) signals from the inferior olive neuron. In the case of well-matched PF signals, they are strongly depressed through strong long-term depression (LTD) by the instructor CF signals due to good association between the in-phase PF and the instructor CF signals. On the other hand, practically no LTD occurs for the ill-matched PF signals because most of them have no association with the instructor CF signals. This kind of "effective" depression at the PF-PC synapses coordinates firings of PCs effectively, which then makes effective inhibitory coordination on the cerebellar nucleus neuron [which elicits conditioned response (CR; eyeblink)]. When the learning trial passes a threshold, acquisition of CR begins. In this case, the timing degree of CR becomes good due to presence of the ill-matched firing group which plays a role of protection barrier for the timing. With further increase in the number of trials, strength of CR (corresponding to the amplitude of eyelid closure) increases due to strong LTD in the well-matched firing group, while its timing degree decreases. In this way, the well- and the ill-matched firing groups play their own roles for the strength and the timing of CR, respectively. Thus, with increasing the number of learning trials, the (overall) learning efficiency degree (taking into consideration both timing and strength of CR) for the CR is increased, and eventually it becomes saturated. Finally, we also discuss dependence of the variety degree for firing patterns of the GR cells and the saturated learning efficiency degree of the CR on and their relations.

Pavlovian eyeblink conditioning is severely impaired in tottering mice.

Cacna1a encodes the pore-forming α1A subunit of CaV2.1 voltage-dependent calcium channels, which regulate neuronal excitability and synaptic transmission. Purkinje cells in the cortex of cerebellum abundantly express these CaV2.1 channels. Here, we show that homozygous tottering (tg) mice, which carry a loss-of-function Cacna1a mutation, exhibit severely impaired learning in Pavlovian eyeblink conditioning, which is a cerebellar-dependent learning task. Performance of reflexive eyeblinks is unaffected in tg mice. Transient seizure activity in tg mice further corrupted the amplitude of eyeblink conditioned responses. Our results indicate that normal calcium homeostasis is imperative for cerebellar learning and that the oscillatory state of the brain can affect the expression thereof.NEW & NOTEWORTHY In this study, we confirm the importance of normal calcium homeostasis in neurons for learning and memory formation. In a mouse model with a mutation in an essential calcium channel that is abundantly expressed in the cerebellum, we found severely impaired learning in eyeblink conditioning. Eyeblink conditioning is a cerebellar-dependent learning task. During brief periods of brain-wide oscillatory activity, as a result of the mutation, the expression of conditioned eyeblinks was even further disrupted.

Propranolol produces short-term facilitation of extinction in a rabbit model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a learning-based anxiety disorder with significant public health challenges due to difficulties in treating the complex, multiple symptomology. We have developed an animal model of PTSD, based on Pavlovian eyeblink conditioning in rabbits, that addresses two key features: conditioned responses (CRs) to cues associated with an aversive event and a form of conditioned hyperarousal referred to as conditioning-specific reflex modification (CRM). We have found previously that unpaired extinction is ideal for reducing both CRs and CRM simultaneously and shows sensitivity to systemic serotonergic and glutamatergic manipulations. The following study aimed to extend our work to examine the role of the noradrenergic system, dysregulation of which is strongly implicated as part of the neurobiology of PTSD and which may also play a role in the balance shift from fear reconsolidation to extinction during treatment. The goal of the following two studies was to examine whether the β-adrenergic receptor antagonist propranolol combined with either a full or brief course of unpaired extinction treatment could enhance extinction of CRs and/or CRM. Results showed a within-session facilitation of propranolol on extinction of CRs, particularly during the first extinction session, and a short-term enhancement of extinction of CRM when extinction treatment was brief. However, neither benefit translated to long-term extinction retention for the majority of subjects. Findings suggest that propranolol may provide the most therapeutic benefit in situations of high arousal early in treatment, which may be more important for future patient compliance rather than long-term treatment outcomes.

Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice.

While research on the cerebellar cortex is crystallizing our understanding of its function in learning behavior, many questions surrounding its downstream targets remain. Here, we evaluate the dynamics of cerebellar interpositus nucleus (IpN) neurons over the course of Pavlovian eyeblink conditioning. A diverse range of learning-induced neuronal responses was observed, including increases and decreases in activity during the generation of conditioned blinks. Trial-by-trial correlational analysis and optogenetic manipulation demonstrate that facilitation in the IpN drives the eyelid movements. Adaptive facilitatory responses are often preceded by acquired transient inhibition of IpN activity that, based on latency and effect, appear to be driven by complex spikes in cerebellar cortical Purkinje cells. Likewise, during reflexive blinks to periocular stimulation, IpN cells show excitation-suppression patterns that suggest a contribution of climbing fibers and their collaterals. These findings highlight the integrative properties of subcortical neurons at the cerebellar output stage mediating conditioned behavior.

Video-based data acquisition system for use in eye blink classical conditioning procedures in sheep.

Pavlovian eye blink conditioning (EBC) has been extensively studied in humans and laboratory animals, providing one of the best-understood models of learning in neuroscience. EBC has been especially useful in translational studies of cerebellar and hippocampal function. We recently reported a novel extension of EBC procedures for use in sheep, and now describe new advances in a digital video-based system. The system delivers paired presentations of conditioned stimuli (CSs; a tone) and unconditioned stimuli (USs; an air puff to the eye), or CS-alone "unpaired" trials. This system tracks the linear distance between the eyelids to identify blinks occurring as either unconditioned (URs) or conditioned (CRs) responses, to a resolution of 5 ms. A separate software application (Eye Blink Reviewer) is used to review and autoscore the trial CRs and URs, on the basis of a set of predetermined rules, permitting an operator to confirm (or rescore, if needed) the autoscore results, thereby providing quality control for accuracy of scoring. Learning curves may then be quantified in terms of the frequencies of CRs over sessions, both on trials with paired CS-US presentations and on CS-alone trials. The latency to CR onset, latency to CR peak, and occurrence of URs are also obtained. As we demonstrated in two example cases, this video-based system provides efficient automated means to conduct EBC in sheep and can facilitate fully powered studies with multigroup designs that involve paired and unpaired training. This can help extend new studies in sheep, a species well suited for translational studies of neurodevelopmental disorders resulting from gestational exposure to drugs, toxins, or intrauterine distress.

Bidirectional Plasticity of Purkinje Cells Matches Temporal Features of Learning

Many forms of learning require temporally ordered stimuli. In Pavlovian eyeblink conditioning, a conditioned stimulus (CS) must precede the unconditioned stimulus (US) by at least about 100 ms for learning to occur. Conditioned responses are learned and generated by the cerebellum. Recordings from the cerebellar cortex during conditioning have revealed CS-triggered pauses in the firing of Purkinje cells that likely drive the conditioned blinks. The predominant view of the learning mechanism in conditioning is that long-term depression (LTD) at parallel fiber (PF)-Purkinje cell synapses underlies the Purkinje cell pauses. This raises a serious conceptual challenge because LTD is most effectively induced at short CS-US intervals, which do not support acquisition of eyeblinks. To resolve this discrepancy, we recorded Purkinje cells during conditioning with short or long CS-US intervals. Decerebrated ferrets trained with CS-US intervals ≥150 ms reliably developed Purkinje cell pauses, but training with an interval of 50 ms unexpectedly induced increases in CS-evoked spiking. This bidirectional modulation of Purkinje cell activity offers a basis for the requirement of a minimum CS-US interval for conditioning, but we argue that it cannot be fully explained by LTD, even when previous in vitro studies of stimulus-timing-dependent LTD are taken into account.

Axonal Sprouting and Formation of Terminals in the Adult Cerebellum during Associative Motor Learning

Plastic changes in the efficacy of synapses are widely regarded to represent mechanisms underlying memory formation. So far, evidence for learning-dependent, new neuronal wiring is limited. In this study, we demonstrate that pavlovian eyeblink conditioning in adult mice can induce robust axonal growth and synapse formation in the cerebellar nuclei. This de novo wiring is both condition specific and region specific because it does not occur in pseudoconditioned animals and is particularly observed in those parts of the cerebellar nuclei that have been implicated to be involved in this form of motor learning. Moreover, the number of new mossy fiber varicosities in these parts of the cerebellar nuclei is positively correlated with the amplitude of conditioned eyelid responses. These results indicate that outgrowth of axons and concomitant occurrence of new terminals may, in addition to plasticity of synaptic efficacy, contribute to the formation of memory.

Children with Specific Language Impairment are not impaired in the acquisition and retention of Pavlovian delay and trace conditioning of the eyeblink response

Three converging lines of evidence have suggested that cerebellar abnormality is implicated in developmental language and literacy problems. First, some brain imaging studies have linked abnormalities in cerebellar grey matter to dyslexia and specific language impairment (SLI). Second, theoretical accounts of both dyslexia and SLI have postulated impairments of procedural learning and automatisation of skills, functions that are known to be mediated by the cerebellum. Third, motor learning has been shown to be abnormal in some studies of both disorders. We assessed the integrity of face related regions of the cerebellum using Pavlovian eyeblink conditioning in 7–11year-old children with SLI. We found no relationship between oral language skills or literacy skills with either delay or trace conditioning in the children. We conclude that this elementary form of associative learning is intact in children with impaired language or literacy development.

Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning.

Neuronal Correlates of Cross-Modal Transfer in the Cerebellum and Pontine Nuclei

Cross-modal transfer occurs when learning established with a stimulus from one sensory modality facilitates subsequent learning with a new stimulus from a different sensory modality. The current study examined neuronal correlates of cross-modal transfer of pavlovian eyeblink conditioning in rats. Neuronal activity was recorded from tetrodes within the anterior interpositus nucleus (IPN) of the cerebellum and basilar pontine nucleus (PN) during different phases of training. After stimulus preexposure and unpaired training sessions with a tone conditioned stimulus (CS), light CS, and periorbital stimulation unconditioned stimulus (US), rats received associative training with one of the CSs and the US (CS1-US). Training then continued on the same day with the other CS to assess cross-modal transfer (CS2-US). The final training session included associative training with both CSs on separate trials to establish stronger cross-modal transfer (CS1/CS2). Neurons in the IPN and PN showed primarily unimodal responses during pretraining sessions. Learning-related facilitation of activity correlated with the conditioned response (CR) developed in the IPN and PN during CS1-US training. Subsequent CS2-US training resulted in acquisition of CRs and learning-related neuronal activity in the IPN but substantially less little learning-related activity in the PN. Additional CS1/CS2 training increased CRs and learning-related activity in the IPN and PN during CS2-US trials. The findings suggest that cross-modal neuronal plasticity in the PN is driven by excitatory feedback from the IPN to the PN. Interacting plasticity mechanisms in the IPN and PN may underlie behavioral cross-modal transfer in eyeblink conditioning.

Effect of Conditioned Stimulus Parameters on Timing of Conditioned Purkinje Cell Responses

Pavlovian eyeblink conditioning is a useful experimental model for studying adaptive timing, an important aspect of skilled movements. The conditioned response (CR) is precisely timed to occur just before the onset of the expected unconditioned stimulus (US). The timing can be changed immediately, however, by varying parameters of the conditioned stimulus (CS). It has previously been shown that increasing the intensity of a peripheral CS or the frequency of a CS consisting of a train of stimuli to the mossy fibers shortens the latency of the CR. The adaptive timing of behavioral CRs probably reflects the timing of an underlying learned inhibitory response in cerebellar Purkinje cells. It is not known how the latency of this Purkinje cell CR is controlled. We have recorded form Purkinje cells in conditioned decerebrate ferrets while increasing the intensity of a peripheral CS or the frequency of a mossy fiber CS. We observe changes in the timing of the Purkinje cell CR that match the behavioral effects. The results are consistent with the effect of CS parameters on behavioral CR latency being caused by corresponding changes in Purkinje cell CRs. They suggest that synaptic temporal summation may be one of several mechanisms underlying adaptive timing of movements.

Bilateral nature of the conditioned eyeblink response in the rabbit: Behavioral characteristics and potential mechanisms.

In Pavlovian eyeblink conditioning, the conditioned response (CR) is highly lateralized to the eye to which the unconditioned stimulus (US) has been directed. However, the initial conditioning of one eye can facilitate subsequent conditioning of the other eye, a phenomenon known as the intereye transfer (IET) effect. Because a conditioned emotional response (CER), as well as the eyeblink CR, is acquired during eyeblink conditioning and influences the development of the CR, the CER acquired in initial training can plausibly account for the IET effect. To evaluate this possibility, the present study utilized previously determined eyeblink conditioning procedures that effectively decouple the degree of CER and CR development to investigate the IET effect. In each of 3 experiments rabbits were initially trained with comparison procedures that differentially favored the development of the eyeblink CR or the CER, prior to a shift of the US to the alternate eye. The observed differences in the IET suggest that the effect depends largely on the specific development of eyeblink CRs rather than the CER. The neurobiological implications of this apparent bilaterality of the eyeblink CR are discussed.

Discriminative delay Pavlovian eyeblink conditioning in veterans with and without posttraumatic stress disorder

Background Impaired eyeblink (EB) classical conditioning using a delay paradigm has previously been shown in combat veterans, as well as in a group of depressed adults, compared to normal individuals. Significant deficits in immediate memory (IM) in combat PTSD+ veterans, compared to normal controls, have also been previously shown, but these differences became non-significant after controlling for level of self-reported depression. Furthermore, EB conditioning has been shown to be significantly correlated with heart rate variability (HRV) in normal adults. The present study examined how depression (self-reported), IM, and resting HRV are related to discriminative delay classical EB conditioning in veterans with and without PTSD. Method Three groups of subjects (combat PTSD+, combat PTSD−, and non-combat PTSD−) were assessed for self-report of depression and anxiety, as well as IM and HRV. Subjects received a single session of discriminative EB classical conditioning in which the conditioned stimulus (CS) was a light signal (either red or green) compounded with a tone. On CS+ trials, the light-tone compound stimulus co-terminated with a corneal airpuff (unconditioned stimulus, US), thus producing a delay paradigm. On CS− trials the appropriate light-tone stimulus was presented but not followed by the airpuff US. EB amplitude and frequency were recorded. Results PTSD+ subjects had greater self-reported depression and anxiety scores than the two control groups, as well as lower scores on a measure of IM. However, the IM difference was not significant after the effects of self-reported depression and anxiety were controlled. EB CR amplitude was significantly greater to CS+ than CS− for all three groups. EB amplitude to both the US (airpuff) and the CS+ declined over trials, but was significantly lower in the combat PTSD+ group compared to the combined PTSD− groups. Subjects who reached an EB CR acquisition criterion had significantly greater scores on IM than those who did not reach criterion. Factor analysis of the entire data set revealed four factors corresponding to (1) self-reported depression and anxiety, (2) IM, (3) HRV, and (4) EB amplitude. EB frequency was significantly predicted by IM and HRV. Conclusions These data extend our previous results by showing deficits in EB conditioning among combat PTSD+ veterans that were associated with lower IM and resting HRV, but were not associated with self-report of depression.

Acquisition, Extinction, and Reacquisition of a Cerebellar Cortical Memory Trace

Associative learning in the cerebellum underlies motor memories and probably also cognitive associations. Pavlovian eyeblink conditioning, a widely used experimental model of such learning, depends on the cerebellum, but the memory locus within the cerebellum as well as the underlying mechanisms have remained controversial. To date, crucial information on how cerebellar Purkinje cells change their activity during learning has been ambiguous and contradictory, and there is no information at all about how they behave during extinction and reacquisition. We have now tracked the activity of single Purkinje cells with microelectrodes for up to 16 h in decerebrate ferrets during learning, extinction, and relearning. We demonstrate that paired peripheral forelimb and periocular stimulation, as well as paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibers) consistently causes a gradual acquisition of an inhibitory response in Purkinje cell simple spike firing. This conditioned cell response has several properties that matches known features of the behavioral conditioned response. The response latency varies with the interstimulus interval, and the response maximum is adaptively timed to precede the unconditioned stimulus. Across training trials, it matches behavioral extinction to unpaired stimulation and also the substantial savings that occur when paired stimulation is reinstated. These data suggest that many of the basic behavioral phenomena in eyeblink conditioning can be explained at the level of the single Purkinje cell.

Effect of serotonin depletion on 5-HT2A-mediated learning in the rabbit: evidence for constitutive activity of the 5-HT2A receptor in vivo

Associative learning during Pavlovian eyeblink conditioning has been shown to be regulated by 5-HT2A receptors. The existence of inverse agonists that retard learning through an action at the 5-HT2A receptor suggests the existence of constitutive activity at that receptor and that depletion of serotonin should have minimal effects on learning. We examined whether depletion of serotonin would impair trace eyeblink conditioning or the enhancement of conditioning produced by the agonist lysergic acid diethylamide (LSD) and the retardation of conditioning produced by the inverse agonist MDL11,939. Animals received bilateral intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) at doses of 760 or 1,140 microg/side (1.88 or 2.82 micromol/side) and were later exposed to eight daily conditioning sessions. Serotonin depletion produced by the lower dose of 5,7-DHT was 71 and 72% in cortex and hippocampus, respectively, with no change in 5-HT2A receptor density, no effect on learning, and no effect on the ability of LSD to enhance and MDL11,939 to retard learning. The higher dose of 5,7-DHT produced serotonin decreases of 85 and 90% in cortex and hippocampus, respectively, accompanied by a 96% decrease in the density of the serotonin transporter, but no significant effect on learning. Pavlovian trace eyeblink conditioning is regulated predominantly by the constitutive activity of the 5-HT2A receptor rather than by serotonin release onto the receptor during learning. It was suggested that the 5-HT2A receptor regulates learning by modulating the release of dopamine, acetylcholine, and glutamate, transmitters known to affect eyeblink conditioning.

The Neuroscience of Mammalian Associative Learning

Mammalian associative learning is organized into separate anatomically defined functional systems. We illustrate the organization of two of these systems, Pavlovian fear conditioning and Pavlovian eyeblink conditioning, by describing studies using mutant mice, brain stimulation and recording, brain lesions and direct pharmacological manipulations of specific brain regions. The amygdala serves as the neuroanatomical hub of the former, whereas the cerebellum is the hub of the latter. Pathways that carry information about signals for biologically important events arrive at these hubs by circuitry that depends on stimulus modality and complexity. Within the amygdala and cerebellum, neural plasticity occurs because of convergence of these stimuli and the biologically important information they predict. This neural plasticity is the physical basis of associative memory formation, and although the intracellular mechanisms of plasticity within these structures share some similarities, they differ significantly. The last Annual Review of Psychology article to specifically tackle the question of mammalian associative learning ( Lavond et al. 1993 ) persuasively argued that identifiable "essential" circuits encode memories formed during associative learning. The next dozen years saw breathtaking progress not only in detailing those essential circuits but also in identifying the essential processes occurring at the synapses (e.g., Bi & Poo 2001, Martinez & Derrick 1996 ) and within the neurons (e.g., Malinow & Malenka 2002, Murthy & De Camilli 2003 ) that make up those circuits. In this chapter, we describe the orientation that the neuroscience of learning has taken and review some of the progress made within that orientation.

Medial Prefrontal Lesions and Pavlovian Eyeblink and Heart Rate Conditioning: Effects of Partial Reinforcement on Delay and Trace Conditioning in Rabbits (Oryctolagus cuniculus).

Effects of continuous (100%) versus partial (25%) reinforcement were studied on Pavlovian delay and trace eyeblink conditioning in rabbits (Oryctolagus cuniculus) with either lesions to the medial prefrontal cortex (mPFC) or sham lesions. Concomitant heart rate changes evoked by the conditioned stimulus were also assessed. Partial reinforcement retarded eyeblink conditioning in both the trace and delay paradigm, but this impairment was greater during trace conditioning and in rabbits with mPFC lesions. Accompanying conditioned stimulus-evoked heart rate slowing was attenuated under all conditions by the mPFC lesions, although this result was not always statistically significant.