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Using pavlovian higher-order conditioning paradigms to investigate the neural substrates of emotional learning and memory.

In first-order Pavlovian conditioning, learning is acquired by pairing a conditioned stimulus (CS) with an intrinsically motivating unconditioned stimulus (US; e.g., food or shock). In higher-order Pavlovian conditioning (sensory preconditioning and second-order conditioning), the CS is paired with a stimulus that has motivational value that is acquired rather than intrinsic. This review describes some of the ways higher-order conditioning paradigms can be used to elucidate substrates of learning and memory, primarily focusing on fear conditioning. First-order conditioning, second-order conditioning, and sensory preconditioning allow for the controlled demonstration of three distinct forms of memory, the neural substrates of which can thus be analyzed. Higher-order conditioning phenomena allow one to distinguish more precisely between processes involved in transmission of sensory or motor information and processes involved in the plasticity underlying learning. Finally, higher-order conditioning paradigms may also allow one to distinguish between processes involved in behavioral expression of memory retrieval versus processes involved in memory retrieval itself.

Animals↗

Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses.

Among the many issues surrounding the involvement of the cerebellum in motor learning, the relative roles of the cerebellar cortex and cerebellar nuclei in Pavlovian conditioning have been particularly difficult to assess. While previous studies have investigated the effects of cerebellar cortex lesions on the acquisition and retention of conditioned movements, we have examined the effects of these lesions on the timing of Pavlovian eyelid responses. The rationale for this approach arises from previous studies indicating that this timing is a component of Pavlovian eyelid responses that is learned and that involves temporal discrimination. To permit within-animal comparisons, rabbits were trained to produce differently timed responses to high- and low-frequency auditory conditioned stimuli (CSs). Before the lesion the conditioned responses to both CSs were appropriately timed--each peaked near the time at which the unconditioned stimulus was presented for that CS. However, after the lesion both CSs could elicit similarly timed conditioned responses that peaked inappropriately at very short latencies. The changes in responses timing were sensitive to the size of the lesion, particularly its rostral-caudal extent. Similar results were obtained in animals trained with one CS, indicating that the disruption of response timing is not related to impaired auditory discrimination. Because response timing is learned and therefore requires synaptic plasticity, these data suggest that there are at least two sites of plasticity involved in the motor expression of Pavlovian eyelid responses. Plasticity at one site is necessary for the learned timing of conditioned responses, while plasticity at another site is revealed by the inappropriately timed responses observed following removal of the cerebellar cortex. This lesion-induced dissociation of the expression of motor responses and their learned timing supports a synthesis of competing views by suggesting that motor learning involves both the cerebellar cortex and cerebellar nuclei. We hypothesize that motor learning involves a decrease in strength of the granule cell-Purkinje cell synapses (e.g., Ito and Kano, 1982) in the cerebellar cortex and an increase in strength of the mossy fiber-cerebellar nuclei synapses (e.g., Racine et al., 1986). Finally, these data suggest that the cerebellar cortex may mediate the temporal discriminations that are necessary for the learned timing of conditioned responses.

Animals↗

Cooperation and competition between the dorsal hippocampus and lateral amygdala in spatial discrimination learning.

The conditioned cue preference (CCP) was used to study how rats discriminate between adjacent arms on a radial maze. Chai and White (Behav Neurosci 2004, 118:770-784) showed that an intact dorsal hippocampus is required to learn this discrimination and that an amygdala-based conditioned approach response that produces an equal tendency to enter both arms is simultaneously acquired. In the present experiments, rats were preexposed to the maze with no food and trained by alternately confining them at the ends of two adjacent arms, one that contained food and one that did not. When given a choice between these arms with no food present, the rats spent more time on their food-paired arms, suggesting they had learned to discriminate their locations. Temporary inactivation of the dorsal hippocampus with muscimol during confinement on the food-paired arm had no effect on the discrimination, but inactivation while on the no-food arm impaired it. This pattern of effects was reversed in rats with amygdala lesions (inactivation on the food-paired arm impaired, but inactivation on the no-food arm had no effect on the discrimination), showing that hippocampus-based and amygdala-based learning interact to influence the behavior of normal rats in this situation. The dorsal hippocampus learns about locations that contain food and about locations that do not contain food. The amygdala-based tendency to enter the food-paired arm cooperates with hippocampus-based foraging for food on the food-paired, but the amygdala-based tendency to enter the no-food arm competes with hippocampus-based learning about the absence of food on that arm.

Amygdala↗

Auditory feedback and memory for music performance: sound evidence for an encoding effect.

Research on the effects of context and task on learning and memory has included approaches that emphasize processes during learning (e.g., Craik & Tulving, 1975) and approaches that emphasize a match of conditions during learning with conditions during a later test of memory (e.g., Morris, Bransford, & Franks, 1977; Proteau, 1992; Tulving & Thomson, 1973). We investigated the effects of auditory context on learning and retrieval in three experiments on memorized music performance (a form of serial recall). Auditory feedback (presence or absence) was manipulated while pianists learned musical pieces from notation and when they later played the pieces from memory. Auditory feedback during learning significantly improved later recall. However, auditory feedback at test did not significantly affect recall, nor was there an interaction between conditions at learning and test. Auditory feedback in music performance appears to be a contextual factor that affects learning but is relatively independent of retrieval conditions.

Adolescent↗

Amnesic patients can benefit from instructions to use imagery: evidence against the cognitive mediation hypothesis.

Six bi-temporal amnesics and seven Korsakoff patients were compared on paired associate learning under four different conditions, rote learning, images provided, images self generated, and verbal mediation. Both imagery manipulations produced better learning than either rote learning or verbal mediation but the latter two conditions did not differ. The data are interpreted as arguing against an interpretation of amnesia in terms of cognitive mediation. The two patient groups behaved similarly in the experiment, thus suggesting that immediate recall of paired-associates learning does not differentiate different forms of organic amnesia.

Amnesia↗

Modification of the discharge of lateral geniculate neurons during visual learning.

Visually conditioned heart rate change in the pigeon has been developed as a vertebrate model system for cellular analysis of associative learning. Previous studies have characterized the behavior, largely delineated the neural circuitry mediating the conditioning, and estimated the central processing time for the conditioned response. Most recently, this system has been used to investigate neuronal activity during conditioning along the visual pathways that transmit the conditioned stimulus (CS) information. It was first shown that neither maintained nor CS-evoked discharge of retinal ganglion cells changes during conditioning. Subsequently, we found that the thalamic and telencephalic components of the ascending tectofugal pathway show associative modification. We report here studies of the thalamofugal pathway, the avian homolog of the mammalian geniculocortical system. Single-cell activity was recorded in the thalamic relay of this pathway, the dorsal lateral geniculate equivalent (LGNe). This provided an opportunity to evaluate the generality of the training-induced modification found along the tectofugal pathway, and to determine if such modification occurs as peripherally as retinorecipient neurons. The results show that almost all LGNe neurons (97%) respond phasically to the onset of whole-field illumination. Most (94%) also respond to the unconditioned stimulus (US), footshock, some with increased and others with decreased discharge. Of cells receiving convergent input, those responding with decreased discharge to the US showed associative change (52%). Neurons that did not respond to both the CS and US, or that responded to the US with increased discharge, did not show associative modification. These findings suggest that the visual pathways transmitting CS information are not merely input lines, but undergo training-induced modification; such modification can occur as peripherally as the retinorecipient neurons of these pathways; and CS-US convergence is necessary but not sufficient for associative modification, since modifiability is apparently contingent on specific US response properties.

Analysis of Variance↗

Signal detection analysis of conditioning data.

Signal detection analysis of learning and conditioning data provides for a greater distinction to be made between learning and performance through the use of the two signal detection parameters, d' and B. The use of the two parameters permits alternative interpretation of several types of data sets discussed. This analytic technique may be used with either discrete trial or free-response data. The present article reveiws applications of signal detection parameters in the literature, and provides for their extension to other uses.

Conditioning, Classical↗

Dopamine cells respond to predicted events during classical conditioning: evidence for eligibility traces in the reward-learning network.

Behavioral conditioning of cue-reward pairing results in a shift of midbrain dopamine (DA) cell activity from responding to the reward to responding to the predictive cue. However, the precise time course and mechanism underlying this shift remain unclear. Here, we report a combined single-unit recording and temporal difference (TD) modeling approach to this question. The data from recordings in conscious rats showed that DA cells retain responses to predicted reward after responses to conditioned cues have developed, at least early in training. This contrasts with previous TD models that predict a gradual stepwise shift in latency with responses to rewards lost before responses develop to the conditioned cue. By exploring the TD parameter space, we demonstrate that the persistent reward responses of DA cells during conditioning are only accurately replicated by a TD model with long-lasting eligibility traces (nonzero values for the parameter lambda) and low learning rate (alpha). These physiological constraints for TD parameters suggest that eligibility traces and low per-trial rates of plastic modification may be essential features of neural circuits for reward learning in the brain. Such properties enable rapid but stable initiation of learning when the number of stimulus-reward pairings is limited, conferring significant adaptive advantages in real-world environments.

Action Potentials↗

Amygdalar unit activity during three learning tasks: eyeblink classical conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning.

Neural activity in central and basolateral amygdala nuclei (CeA and BLA, respectively) was recorded during delay eyeblink conditioning, Pavlovian fear conditioning, and signaled barpress avoidance. During paired training, the CeA exhibited robust learning-related excitatory activity during all 3 tasks. By contrast, the BLA exhibited minimal activity during eyeblink conditioning, while demonstrating pronounced increases in learning-related excitatory responsiveness during fear conditioning and barpress avoidance. In addition, the relative amount of amygdalar activation observed appeared to be related to the relative intensity of the unconditioned stimulus and somatic requirements of the task. Results suggest the CeA mediates the Pavlovian association between sensory stimuli and the BLA mediates the modulation of instrumental responding through the assignment of motivational value to the unconditioned stimulus.

Action Potentials↗

Vicarious conditioned acceleration: successful observational learning of an aversive Pavlovian stimulus contingency.

Five rats (observers) were trained to avoid unsignalled shocks in a shuttlebox and then habituated to brief light presentations. They were next confined on an observation platform while another rat (model) received light-shock pairings in the opposite compartment. The observers were exposed only to the sight and sound of the model during classical conditioning and were not shocked themselves. Test presentations of the light during subsequent avoidance sessions produced response rate increases (vicarious conditioned acceleration) comparable to those obtained in other studies where the avoidance animals were used in classical conditioning. Following sessions in which the model was not shocked after the light, the light presentations during avoidance eventually failed to elicit any response increases in the observers. When the model was again shocked, immediate recovery of avoidance acceleration occurred in the observers during the light.

Animals↗