Memory, or the ability to recall previously learned information, has been evaluated among different populations. Some previous research has utilized different forms of verbal prompts to assist participants in recalling associations. These verbal prompts can be categorized as simple or elaborative. Although previous research has indicated that both forms of verbal prompts are effective in teaching individuals to relate stimulus pairs, there is currently no research that compares these prompting methods. Therefore, the current study sought to compare simple and elaborative prompts for teaching a picture-association task with four typically developing preschool children. Data suggest that elaborative prompts were more effective in teaching associations across all participants and resulted in similar levels of maintenance at 1-week and 1-month probes. Keywords. associative learning, memory, verbal prompts

The primary motor cortex (M1) is an important site for learning new motor skills. While rewardis known to both enhance and accelerate motor learning, the mechanism by which reward exertsthese effects remains unclear. Previous studies in primates have demonstrated reward-relatedactivity in M1, however, it is not known whether reward is represented among different neuronalcell types in M1, or if the representations change over the course of reward-based associativelearning. We begin by reviewing advances in optogenetic methods that have enabled thedissection of cortical circuits underlying sensorimotor behaviours with a special focus on thefunctional roles of cell-type specific connections in governing sensorimotor informationprocessing and learning and memory. We then used in vivo, two-photon calcium imaging tocharacterize reward and reward-related responses in pyramidal neurons (PNs), PV-INs, SST-INsand VIP-INs while mice simultaneously performed a head-fixed auditory classical conditioningtask. We found that different cell types had distinct responses to the conditioned stimulus (CS)and to reward, and these responses underwent differential changes over the course of associativelearning. Notably, VIP-INs preferentially represented reward and their reward responsesincreased with learning, while PV-INs preferentially represented the CS, and their CS responsesincreased with learning. Lastly, to identify which brain regions might provide reward-relatedinput to VIP-INs, we performed cell-type specific monosynaptic rabies tracing and generatedcomparative brain-wide maps of input to VIP-INs, PV-INs, SST-INs and PNs in M1. Weidentified preferential input from the orbital frontal cortex (ORB) to VIP-INs compared to theother IN subtypes. These results suggest that ORB may convey reward-related input to VIP-INsand thereby disinhibit local MOP circuitry during reward-based learning. Together, these studiesprovide a potential mechanism for how reward modulates motor learning.

The medial prefrontal cortex (mPFC) plays a critical role in the organization of goal directed behavior. This role is suggested by the anatomy of mPFC as the region rests at the top of a complex cortical and sub-cortical hierarchy, receives convergent sensory and motor information from multiple modalities, and is the target of modulatory brainstem nuclei that respond to prediction and reward. Given these observations, it was hypothesized that mPFC neurons store associations between stimuli when the stimuli contribute to the prediction of reward. To test this hypothesis, neural ensemble spiking activity was recorded in the mPFC as rats performed a paired-associate discrimination task. In one condition, both elements of the paired-associate stimulus-sequence provided information about reward delivery. In another condition, only the first stimulus contributed to the prediction. As hypothesized, stimulus-selective, prospective delay activity was observed during sequences in which both elements contributed to reward-prediction. Unexpectedly, however, selective delay responses were associated with slight variations in head position and thus were not necessarily generated by intrinsic mnemonic processes. Interestingly, the sensitivity of neurons to head position was greatest during intervals when reward delivery was certain. These result suggest that a major portion of delay activity in the rat mPFC reflects task-relevant sensory-motor activity, possibly related to behavioral strategies rather than to the local storage of stimulus-stimulus associations. These observations agree with evidence suggesting that mPFC neurons are particularly responsive during the performance of actions related to the acquisition of reward. These results also indicate that considerable attention must be given to the monitoring of sensory-motor variables during delay tasks as slight changes in position can produce activity that appears to be driven by intrinsic mechanisms. It is further suggested that such activity may perform an important role in memory guided behavior, although this role may contrast sharply with standard theories of delay activity and short term memory storage. In particular, it is suggested that delay activity observed in the prefrontal cortex may correspond to the maintenance of memories that are 'stored' in the body or in the environment in the forms of embodied or situated behaviors.

Pavlov (1927) first reported that following appetitive conditioning of multiple stimuli, extinction of one CS attenuated responding to others which had not undergone direct extinction. Four experiments with rat subjects investigated potential mechanisms of this secondary extinction effect. Experiment 1 assessed whether secondary extinction would be more likely to occur with target CSs that have themselves undergone some prior extinction. Two CSs were initially paired with shock. One CS was subsequently extinguished before the second CS was tested. The target CS was partially extinguished for half the rats and not extinguished CS for the other half. A robust secondary extinction effect was obtained with the non-extinguished target CS. Experiment 2 investigated whether secondary extinction occurs if the target CS is tested outside the context where the first CS is extinguished. Despite the context switch secondary extinction was observed. Extinction of one CS was also found to thwart renewal of suppression to a second CS when it was tested in a neutral context. Experiment 3 examined whether secondary extinction can be attributed to mediated generalization caused by association of the CSs with a common US during conditioning. Rats received conditioning with three CSs and then extinction with one of them. Secondary extinction was observed with a shock-associated CS when the extinguished CS had been associated with either food pellets or shock, suggesting that secondary extinction is not US-specific and is thus not explained by this mediated generalization mechanism. Experiment 4 examined whether intermixing trials with the two stimuli during conditioning is necessary for secondary extinction to occur. Rats were either conditioned with intermixed trials as in Experiments 1-3, or with blocked trials of each CS presented in conditioning sessions separated by a day. Secondary extinction was observed only in the former condition. The results are consistent with the hypothesis that CSs must be associated with a common temporal context for secondary extinction to occur.

This thesis focuses on probabilistic associative learning. One of the classic effects in this field is the stimulus associability effect for which I derive a statistically optimal inference model and a corresponding approximation that addresses a number of problems with the original account of Mackintosh. My proposed account of associability - a variable learning rate depending on a relative informativeness of stimuli - also accounts of the classic blocking effect \cite{kamin1969predictability} without the need for Prediction Error [PE] computation. Given that blocking was the main impetus for placing PE at the centre of learning theories, I critically re-evaluate other evidence for PE in learning, particularly the recent neuroimaging evidence. I conclude that the brain data are not as clear cut as often presumed. The main shortcoming of the evidence implicating PE in learning is that probabilistic associative learning is mostly described as a transition from one state of belief to another, yet those beliefs are typically observed only after multiple learning episodes and in a very coarse manner. To address this problem, I develop an experimental paradigm and accompanying statistical methods that allow one to infer the beliefs at any given point in time. However, even with the rich data provided by this new paradigm, the blocking effect still cannot provide conclusive evidence for the role of PE in learning. I solve this problem by deriving a novel conceptualisation of learning as a flow in probability space. This allows me to derive two novel effects that can unambiguously distinguish learning that is driven by PE from learning not driven by PE. I call these effectsgeneralized blocking and false blocking, given their inspiration by the original paradigm of Kamin (1969). These two effects can be generalized to the entirety of probability space, rather than just the two specific points provided by the paradigms used by Mackintosh and Kamin, and therefore offer greater sensitivity to differences in learning mechanisms. In particular, I demonstrate that these effects are necessary consequences of PE-driven learning, but not learning based on the relative informativeness of stimuli. Lastly I develop an online experiment to acquire data on the new paradigm from a large number (approximately 2000) of participants recruited via social media. The results of model fitting, together with statistical tests of generalized blocking and false blocking, provide strong evidence against a PE-driven account of learning, instead favouring the relative informativeness account derived at the start of the thesis.

The cockroach, with its large brain and physiological resilience, holds many advantages for the development of behavioral paradigms. The work presented here provides a foundation for, and describes the results of, the implementation of studies of neural correlates of learning and memory on restrained animals.Using the antennal projection response (APR) as an indicator of learning and retention, several learning paradigms have been developed. A visual-olfactory associative and a gustatory-olfactory aversive conditioning paradigm demonstrated a plastic behavior that could be driven in an intact and immobilized cockroach. Conditioning the APR to a visual cue paired with an olfactory cue characterized the role of unilateral and bilateral olfactory input in learning and memory. While unilateral olfactory input is sufficient to learn a visual-olfactory association, bilateral olfactory input is necessary for long-term retention of the association. This comparison identified a critical time period in which memory is consolidated. This time period was subsequently used to analyze gene expression during memory consolidation.The split-brain cockroach preparation was developed to investigate what parts of the brain are necessary and sufficient for learning and retention of a visual-olfactory association; this preparation was also used to examine learning-induced changes in test tissue versus control tissue provided by the same animal. Evidence suggests that half of a brain is sufficient for a visual-olfactory association to be established and sufficient for retention of that association between 12 and 24 hours. However, the entire brain is necessary for long-term memory to be established. Using the split-brain cockroach simultaneously as the control and the test subject, learning-induced alterations in the microglomerular synaptic complexes of the calyces were identified in the trained half, but not in the naïve half.Using the APR, spatial learning and memory was examined. Multiple representations of space were revealed in the brain of the cockroach. Cockroaches represent space in terms of an olfactory gradient map, as well as the visuospatial relationship between objects. When both representations of space can be utilized by the cockroach to localize a cue, the positional visual cue is the one that determines the behavioral response.

Imaging has revealed that brain activation of verbs with verifiable products (‘throw, kick’) activate language areas as well as the motor cortex responsible for the performance of the action described. An exploratory comparison of eye related verbs with no verifiable products (‘observe’) to mouth related verbs with verifiable products (‘shout’) has revealed a similar activation pattern. Thus in order to further study mental action verbs with no verifiable products, the present two-part study used words that were suitable across two modalities (e.g. you can ‘perceive’ both through vision and audition) and compare them to themselves under differing contexts of auditory and visual verbs so as to eliminate any word characteristics differences, as well as explored the two modalities directly. The primary purpose was to delineate whether associative learning or the mirror systems theory might better account for the acquisition of this unique subclass of verbs. Results suggest that Mirror systems theory more likely accounts for the observed cognitive processing differences between the two verbs. Keywords: Verbs, language, Event-related potentials, abstract, associative learning theory, mirror systems theory.

Behavioural phonotaxis (oriented movement in response to sound) is an effective means to quantify auditory perception in acoustically communicating insects. Previous phonotaxis studies on the acoustic parasitoid fly Ormia ochracea (Diptera: Tachinidae) have described stereotyped, reflex-like responses towards auditory stimuli modeled after their preferred cricket hosts, yet their ability to demonstrate plasticity of responses in the context of dynamically changing auditory cues has not previously been described. Using a behavioural sensitization protocol, I compared phonotaxis towards behaviourally irrelevant (non-attractive) test stimuli presented alone, and when preceded with the natural, response-evoking cricket song (attractive). Results demonstrate the cricket song as a sensitizing stimulus mediating phonotaxis towards otherwise non-attractive sounds, and differential walking patterns depending on temporal delay between song offset and test stimulus onset. My findings suggest an ecological purpose of sensitization, allowing flies to maintain orientation towards a cricket host amidst conditions of signal disruption in the environment.

Behavioural phonotaxis (oriented movement in response to sound) is an effective means to quantify auditory perception in acoustically communicating insects. Previous phonotaxis studies on the acoustic parasitoid fly Ormia ochracea (Diptera: Tachinidae) have described stereotyped, reflex-like responses towards auditory stimuli modeled after their preferred cricket hosts, yet their ability to demonstrate plasticity of responses in the context of dynamically changing auditory cues has not previously been described. Using a behavioural sensitization protocol, I compared phonotaxis towards behaviourally irrelevant (non-attractive) test stimuli presented alone, and when preceded with the natural, response-evoking cricket song (attractive). Results demonstrate the cricket song as a sensitizing stimulus mediating phonotaxis towards otherwise non-attractive sounds, and differential walking patterns depending on temporal delay between song offset and test stimulus onset. My findings suggest an ecological purpose of sensitization, allowing flies to maintain orientation towards a cricket host amidst conditions of signal disruption in the environment.

Neuropsychiatric disorders severely impact quality of life in millions of patients, contributing more Disease Affected Life Years (DALYs) than cancer or cardiovascular disease. The human brain is a complex system of 100 billion neurons connected by 100 trillion synapses, and human studies of neural disease focus on network-level circuit activity changes, rather than on cellular mechanisms. To probe for neural dynamics on the cellular level, animal models such as the nematode C. elegans have been used to investigate the biochemical and genetic factors contributing to neurological disease. C. elegans are ideal for neurophysiological studies due to their small nervous system, neurochemical homology to humans, and compatibility with non-invasive neural imaging. To better study the cellular mechanisms contributing to neurological disease, we developed automated analysis methods for characterizing the behaviors and associated neural activity during sleep and learning in C. elegans: two neural functions that involve a high degree of behavioral and neural plasticity. We developed two methods to study previously uncharacterized spontaneous adult sleep in C. elegans. A large microfluidic device facilitates population-wide assessment of long-term sleep behavior over 12 hours including effects of fluid flow, oxygen, feeding, odors, and genetic perturbations. Smaller devices allow simultaneous recording of sleep behavior and neuronal activity. Since the onset of adult sleep is stochastically timed, we developed a closed-loop sleep detection system that delivers chemical stimuli to individual animals during sleep and awake states to assess state-dependent changes to neural responses. Sleep increased the arousal threshold to aversive chemical stimulation, yet sensory neuron (ASH) and first-layer interneuron (AIB) responses were unchanged. This localizes adult sleep-dependent neuromodulation within interneurons presynaptic to the AVA premotor interneurons, rather than afferent sensory circuits. Traditionally, the study of learning in C. elegans observes taxis on agar plates which present variable environmental conditions that can lead to a reduction in test-to-test reproducibility. We also translated the butanone enhancement learning assay such that animals can be trained and tested all within the controlled environment of a microfluidic device. Using this system, we demonstrated that C. elegans are capable of associative learning by observing stimulus evoked behavioral responses, rather than taxis. This system allows for more reproducible results and can be used to seamlessly study stimulus-evoked neural plasticity associated with learning. Together, these systems provide platforms for studying the connections between behavioral plasticity and neural circuit modulation in sleep and learning. We can use these systems to further our understanding of the mechanisms underlying neural regulation, function, and disorder using human disease models in C. elegans.