Climbing fibers provide essential instructive signals for associative learning.

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber (CF) inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. In the present study we used cell-type-specific perturbations of various cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning in mice. Our findings reveal that, although optogenetic stimulation of either CFs or Purkinje cells can drive learning under some conditions, even subtle reductions in CF signaling completely block learning to natural stimuli. We conclude that CFs and corresponding Purkinje cell complex spike events provide essential instructive signals for associative cerebellar learning.

Distinct Hippocampal Oscillation Dynamics in Trace Eyeblink Conditioning Task for Retrieval and Consolidation of Associations.

Trace eyeblink conditioning (TEBC) has been widely used to study associative learning in both animals and humans. In this paradigm, conditioned responses (CRs) to conditioned stimuli (CS) serve as a measure for retrieving learned associations between the CS and the unconditioned stimuli (US) within a trial. Memory consolidation, that is, learning over time, can be quantified as an increase in the proportion of CRs across training sessions. However, how hippocampal oscillations differentiate between successful memory retrieval within a session and consolidation across TEBC training sessions remains unknown. To address this question, we recorded local field potentials (LFPs) from the rat dorsal hippocampus during TEBC and investigated hippocampal oscillation dynamics associated with these two functions. We show that transient broadband responses to the CS were correlated with memory consolidation, as indexed by an increase in CRs across TEBC sessions. In contrast, induced alpha (8-10 Hz) and beta (16-20 Hz) band responses were correlated with the successful retrieval of the CS-US association within a session, as indexed by the difference in trials with and without CR.

Distributional coding of associative learning in discrete populations of midbrain dopamine neurons.

Midbrain dopamine neurons are thought to play key roles in learning by conveying the difference between expected and actual outcomes. Recent evidence suggests diversity in dopamine signaling, yet it remains poorly understood how heterogeneous signals might be organized to facilitate the role of downstream circuits mediating distinct aspects of behavior. Here, we investigated the organizational logic of dopaminergic signaling by recording and labeling individual midbrain dopamine neurons during associative behavior. Our findings show that reward information and behavioral parameters are not only heterogeneously encoded but also differentially distributed across populations of dopamine neurons. Retrograde tracing and fiber photometry suggest that populations of dopamine neurons projecting to different striatal regions convey distinct signals. These data, supported by computational modeling, indicate that such distributional coding can maximize dynamic range and tailor dopamine signals to facilitate specialized roles of different striatal regions.

The role of uncertainty in regulating associative change.

Rescorla (2000, 2001) interpreted his compound test results to show that both common and individual error terms regulate associative change such that the element of a conditioned compound with the greater prediction error undergoes greater associative change than the one with the smaller prediction error. However, it has recently been suggested that uncertainty, not prediction error, is the primary determinant of associative change in people (Spicer et al., 2020, 2022). The current experiments use the compound test in a continuous outcome allergist task to assess the role of uncertainty in associative change, using two different manipulations of uncertainty: outcome uncertainty (where participants are uncertain of the level of the outcome on a particular trial) and causal uncertainty (where participants are uncertain of the contribution of the cue to the level of the outcome). We replicate Rescorla's compound test results in the case of both associative gains (Experiment 1) and associative losses (Experiment 3) and then provide evidence for greater change to more uncertain cues in the case of associative gains (Experiments 2 and 4), but not associative losses (Experiments 3 and 5). We discuss the findings in terms of the notion of theory protection advanced by Spicer et al., and other ways of thinking about the compound test procedure, such as that proposed by Holmes et al. (2019). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Conditioned preferences: Gated by experience, context, and endocrine systems.

Central to the navigation of an ever-changing environment is the ability to form positive associations with places and conspecifics. The functions of location and social conditioned preferences are often studied independently, limiting our understanding of their interplay. Furthermore, a de-emphasis on natural functions of conditioned preferences has led to neurobiological interpretations separated from ecological context. By adopting a naturalistic and ethological perspective, we uncover complexities underlying the expression of conditioned preferences. Development of conditioned preferences is a combination of motivation, reward, associative learning, and context, including for social and spatial environments. Both social- and location-dependent reward-responsive behaviors and their conditioning rely on internal state-gating mechanisms that include neuroendocrine and hormone systems such as opioids, dopamine, testosterone, estradiol, and oxytocin. Such reinforced behavior emerges from mechanisms integrating past experience and current social and environmental conditions. Moreover, social context, environmental stimuli, and internal state gate and modulate motivation and learning via associative reward, shaping the conditioning process. We highlight research incorporating these concepts, focusing on the integration of social neuroendocrine mechanisms and behavioral conditioning. We explore three paradigms: 1) conditioned place preference, 2) conditioned social preference, and 3) social conditioned place preference. We highlight nonclassical species to emphasize the naturalistic applications of these conditioned preferences. To fully appreciate the complex integration of spatial and social information, future research must identify neural networks where endocrine systems exert influence on such behaviors. Such research promises to provide valuable insights into conditioned preferences within a broader naturalistic context.

Pupillary Responses Reflect Dynamic Changes in Multiple Cognitive Factors During Associative Learning in Primates.

Associative learning involves complex interactions of multiple cognitive factors. While adult subjects can articulate these factors verbally, for model animals such as macaques, we rely on behavioral outputs. In our study, we used pupillary responses as an alternative measure to capture these underlying cognitive changes. We recorded the dynamic changes in the pupils of three male macaques when they learned the associations between visual stimuli and reward sizes under the classical Pavlovian experimental paradigm. We found that during the long-term learning process, the gradual changes in the pupillary response reflect the changes in the cognitive state of the animals. The pupillary response can be explained by a linear combination of components corresponding to multiple cognitive factors. These components reflect the impact of visual stimuli on the pupils, the prediction of reward values associated with the visual stimuli, and the macaques' understanding of the current experimental reward rules. The changing patterns of these factors during interday and intraday learning clearly demonstrate the enhancement of current reward-stimulus association and the weakening of previous reward-stimulus association. Our study shows that the dynamic response of pupils can serve as an objective indicator to characterize the psychological changes of animals, understand their learning process, and provide important tools for exploring animal behavior during the learning process.

Encoding of Predictive Associations in Human Prefrontal and Medial Temporal Neurons During Pavlovian Appetitive Conditioning.

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here, we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus, and amygdala while patients of both sexes performed an appetitive Pavlovian conditioning task probing both stimulus-value and stimulus-stimulus associations. Ventromedial prefrontal cortex encoded predictive value along with the amygdala, and also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial frontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning.

Examining the neural basis of unitization: A review.

Associative memory refers to the ability to form and remember associations between individual pieces of information rather than memory for a single object or word. Encoding associations in memory tends to be a more difficult task than item (only) encoding, because associative memory requires encoding multiple items as well as the specific links amongst the items. Accordingly, researchers have worked to identify interventions and strategies to reduce the effort and neural resources required for successful associative memory processing. Unitization is one such strategy that has traditionally been defined as the process by which two or more discrete items are processed, or encoded, such that they are perceived as a single ensemble. The current review explores the neural research on unitization while considering the behavioral benefits that accompany the process.

Optogenetic activation of dopamine D1 receptors in island cells of medial entorhinal cortex inhibits temporal association learning.

A critical feature of episodic memory formation is to associate temporally segregated events as an episode, called temporal association learning. The medial entorhinal cortical-hippocampal (EC-HPC) networks is essential for temporal association learning. We have previously demonstrated that pyramidal cells in the medial EC (MEC) layer III project to the hippocampal CA1 pyramidal cells and are necessary for trace fear conditioning (TFC), which is an associative learning between tone and aversive shock with the temporal gap. On the other hand, Island cells in MECII, project to GABAergic neurons in hippocampal CA1, suppress the MECIII input into the CA1 pyramidal cells through the feed-forward inhibition, and inhibit TFC. However, it remains unknown about how Island cells activity is regulated during TFC. In this study, we report that dopamine D1 receptor is preferentially expressed in Island cells in the MEC. Optogenetic activation of dopamine D1 receptors in Island cells facilitate the Island cell activity and inhibited hippocampal CA1 pyramidal cell activity during TFC. The optogenetic activation caused the impairment of TFC memory recall without affecting contextual fear memory recall. These results suggest that dopamine D1 receptor in Island cells have a crucial role for the regulation of temporal association learning.

Chinese character unitization enhances recollection-based associative recognition: Evidence from fMRI.

Previous research has suggested that familiarity can enhance associative memory after unitization, but the cognitive mechanisms underlying unitization remain debated. To explore the neural mechanisms of associative memory after unitization in the absence of semantic relations, we used Chinese characters as stimuli and recorded participants' blood oxygen level-dependent signals during recognition. Behavioral results showed that after Chinese character unitization, not only the associative performance of recognition (Pr, hit rate minus false alarm rate) and general Pr but also the hit rate and correct rejection rate increased. Neuroimaging results revealed activation of the hippocampus and parahippocampal gyrus during associative recognition in both the unitized and the non-unitized condition, and hippocampal activation increased after unitization. However, activation of the perirhinal cortex was not observed in either condition. These findings, in contrast to those from previous studies on unitization, suggest that Chinese character unitization enhances recollection-based, rather than familiarity-based, associative recognition. This suggests that the encoding of semantic relations during unitization is critical for subsequent familiarity-based associative recognition.

Retardation of acquisition after conditioned inhibition and latent inhibition training in human causal learning.

Inhibitory stimuli are slow to acquire excitatory properties when paired with the outcome in a retardation test. However, this pattern is also seen after simple nonreinforced exposure: latent inhibition. It is commonly assumed that retardation would be stronger for a conditioned inhibitor than for a latent inhibitor, but there is surprisingly little empirical evidence comparing the two in either animals or humans. Thus, retardation after inhibitory training could in principle be attributable entirely to latent inhibition. We directly compared the speed of excitatory acquisition after conditioned inhibition and matched latent inhibition training in human causal learning. Conditioned inhibition training produced stronger transfer in a summation test, but the two conditions did not differ substantially in a retardation test. We offer two explanations for this dissociation. One is that learned predictiveness attenuated the latent inhibition that otherwise would have occurred during conditioned inhibition training, so that retardation in that condition was primarily due to inhibition. The second explanation is that inhibitory learning in these experiments was hierarchical in nature, similar to negative occasion-setting. By this account, the conditioned inhibitor was able to negatively modulate the test excitor in a summation test, but was no more retarded than a latent inhibitor in its ability to form a direct association with the outcome. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The opportunity to compare similar stimuli can reduce the effectiveness of features they hold in common.

In three experiments, rats were given experience of flavored solutions AX and BX, where A and B represent distinctive flavors and X a flavor common to both solutions. In one condition, AX and BX were presented on the same trial separated by a 5-min interval (intermixed preexposure). In another condition, each daily trial consisted of presentations of only AX or only BX (blocked preexposure). The properties acquired by stimulus X were then tested. Experiment 1 showed that after intermixed preexposure X was less able to interfere with a conditioned response established to a different flavor. Experiment 2 showed that X was less effective at overshadowing when trained in compound with another flavor. Simple conditioning, with X as the conditioned stimulus, was not sensitive to the form of preexposure (Experiment 3). These results indicate that the opportunity to compare similar stimuli that is provided by presenting them in close succession can change the properties of features they hold in common, making these features less effective when tested in compound with other stimuli. A loss of effectiveness by such features would contribute to the perceptual learning effect, the enhancement of subsequent discrimination, that is generated by prior exposure to closely spaced similar stimuli. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neural distinctiveness and reinstatement of hippocampal representations support unitization for associations.

The medial temporal lobe (MTL) is critical to associative memory success, yet not all types of associations may be processed in a similar manner within MTL subregions. In particular, previous work suggests intra- and inter-item associations not only exhibit differences in overall rates of recollection, but also recruit different MTL subregions. Whereas intra-item associations, akin to unitization, take advantage of associations between within-item features, inter-item associations form links across discrete items. The current work examines the neural differences between these two types of associations using fMRI and multivoxel analyses. Specifically, the current study examines differences across face-occupation as a function of whether the pairing was viewed as a person performing the given job (intra-item binding) or a person saying they knew someone who had a particular job (inter-item binding). The results show that at encoding, successfully recollected neural patterns related to intra- and inter-item associations are distinct from one another in the hippocampus, parahippocampal and perirhinal cortex. Additionally, the two trial types are reinstated distinctly such that inter-item trials have higher neural reinstatement from encoding to retrieval compared to intra-item trials in the hippocampus. We conclude that intra- and inter- associative pairs may utilize similar neural regions that represent patterns of activation differentially at encoding. However, to reinstate information to the same degree (i.e., subsequently successfully recollected) inter-item associations, that are all encoded in the same manner, may be reinstated more similarly compared to intra-item associations that are encoded by imagining pairs differently and occupation specific. This may indicate that intra-item associations promote more efficient reinstatement.

Perceptual learning after rapidly alternating exposure to taste compounds: Assessment with different indices of generalization.

Exposure to two similar stimuli (AX and BX; e.g., two tastes) reduces the extent to which a conditioned response later established to BX generalizes to AX. This example of perceptual learning is more evident when AX and BX are exposed in an alternating manner (AX, BX, AX, BX,…) than when AX and BX occur in separate blocks (e.g., AX, AX,…BX, BX,…). We examined in male rats (N = 126) the impact of rapid alternation to AX and BX on generalization of a taste aversion from BX to AX. Experiment 1 showed that such alternating presentations (with 5-min intervals between AX and BX) reduced generalization relative to blocked exposure; but only as assessed by consumption levels and not by lick cluster size (an index of hedonic reactions). Experiment 1 also showed that the nature of exposure did not affect how A influenced performance to a novel conditioned taste, Y. Experiment 2 replicated the pattern of results involving the different influences of rapidly alternating and blocked exposure on generalization from BX to AX, and showed that this effect was only evident when rats received access to water during the 5-min intervals between AX and BX. These results reinforce parallels between perceptual learning effects in rats and humans, both at empirical and theoretical levels. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The role of prediction in learned predictiveness.

Learning permits even relatively uninteresting stimuli to capture attention if they are established as predictors of important outcomes. Associative theories explain this "learned predictiveness" effect by positing that attention is a function of the relative strength of the association between stimuli and outcomes. In three experiments we show that this explanation is incomplete: learned overt visual-attention is not a function of the relative strength of the association between stimuli and an outcome. In three experiments, human participants were exposed to triplets of stimuli that comprised (a) a target (that defined correct responding), (b) a stimulus that was perfectly correlated with the presentation of the target, and (c) a stimulus that was uncorrelated with the presentation of the target. Participants' knowledge of the associative relationship between the correlated or uncorrelated stimuli and the target was always good. However, eye-tracking revealed that an attentional bias toward the correlated stimulus only developed when it and target-relevant responding preceded the target stimulus. We propose a framework in which attentional changes are modulated during learning as a function the relative strength of the association between stimuli and the task-relevant response, rather than an association between stimuli and the task-relevant outcome. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association learning: Dopamine and the formation of backward associations.

The activity of dopamine neurons is critical for the ability to learn and update cue-reward associations. New work in rats shows that dopamine transients are also critical for the formation of backward associations in which the reward precedes the neutral stimulus.

Reversal of inhibition by no-modulation training but not by extinction in human causal learning.

One of the many strengths of the Rescorla and Wagner (1972) model is that it accounts for both excitatory and inhibitory learning using a single error-correction mechanism. However, it makes the counterintuitive prediction that nonreinforced presentations of an inhibitory stimulus will lead to extinction of its inhibitory properties. Zimmer-Hart and Rescorla (1974) provided the first of several animal conditioning studies that contradicted this prediction. However, the human data are more mixed. Accordingly, we set out to test whether extinction of an inhibitor occurs in human causal learning after simultaneous feature negative training with a conventional unidirectional outcome. In 2 experiments with substantial sample sizes, we found no evidence of extinction after presentations of the inhibitory stimulus alone in either a summation test or causal ratings. By contrast, 2 "no-modulation" procedures that contradicted the original training contingencies successfully reversed inhibition. These results did not differ substantially as a function of participants' self-reported causal structures (configural/modulation/prevention). We hypothesize that inhibitory learning may be intrinsically modulatory, analogous to negative occasion-setting, even with simultaneous training. This hypothesis would explain why inhibition is reversed by manipulations that contradict modulation but not by simple extinction, as well as other properties of inhibitory learning such as imperfect transfer to another excitor. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A response function that maps associative strengths to probabilities.

Bridging associative and normative theories of animal learning, I show that an associative system can behave as if performing probabilistic inference by using the function f(V) = 1 - e-cV to transform associative strengths (V) into response probabilities. For example, using this function, an associative system can respond normatively to a compound stimulus AB, given previous separate experiences with the components A and B. The CR probability formulae that result from the proposed function have a normative interpretation in terms of statistical decision theory. The formulae also suggest a normative interpretation of stimulus generalization as a heuristic to infer whether different stimuli are likely to convey redundant or independent information about reinforcement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pavlovian summation: Data and theory.

In summation experiments, responding to a compound stimulus is assessed after conditioning a response to each of its components. This simple experiment poses significant challenges to models of associative learning because of substantial variability in results. Here, I introduce a new method to quantify generalization from components to compound in summation experiments, which I apply to over 250 measurements of summation in rabbits, pigeons, rats, and humans. The analysis confirms that more summation occurs with stimuli from different rather than from the same sensory modality, although this is not the sole determinant of summation. A theoretical analysis shows that this finding is best accounted for by a model that includes both element sharing (Rescorla & Wagner, 1972) and element replacement (Brandon et al., 2000) in stimulus representations. I point out remaining gaps in our empirical and theoretical understanding of summation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).