Cortico-Cerebellar Hyper-Connections and Reduced Purkinje Cells Behind Abnormal Eyeblink Conditioning in a Computational Model of Autism Spectrum Disorder

Empirical evidence suggests that children with autism spectrum disorder (ASD) show abnormal behavior during delay eyeblink conditioning. They show a higher conditioned response learning rate and earlier peak latency of the conditioned response signal. The neuronal mechanisms underlying this autistic behavioral phenotype are still unclear. Here, we use a physiologically constrained spiking neuron model of the cerebellar-cortical system to investigate which features are critical to explaining atypical learning in ASD. Significantly, the computer simulations run with the model suggest that the higher conditioned responses learning rate mainly depends on the reduced number of Purkinje cells. In contrast, the earlier peak latency mainly depends on the hyper-connections of the cerebellum with sensory and motor cortex. Notably, the model has been validated by reproducing the behavioral data collected from studies with real children. Overall, this article is a starting point to understanding the link between the behavioral and neurobiological basis in ASD learning. At the end of the paper, we discuss how this knowledge could be critical for devising new treatments.

Training the domestic ferret to discriminate odors associated with wildlife disease

Recent avian influenza infection outbreaks have resulted in global biosecurity and economic concerns. Mallards are asymptomatic for the disease and can potentially spread AI along migratory bird flyways. In a previous study, trained mice correctly discriminated the health status of individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Chemical analyses indicated that avian influenza infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone) in feces. In the current study, domesticated male ferrets (Mustela putorius furo) were trained to display a specific conditioned response (i.e. active scratch alert) in response to a marked increase of acetoin in a presentation of an acetoin:1-octen-3-ol solution. Ferrets rapidly generalized this learned response to the odor of irradiated feces from avian influenza infected mallards. These results suggest that a trained mammalian biosensor could be employed in an avian influenza surveillance program.

Individual Scores for Associative Learning in a Differential Appetitive Olfactory Paradigm Using Binary Logistic Regression Analysis

Numerous invertebrates have contributed to our understanding of the biology of learning and memory. In most cases, learning performance is documented for groups of individuals, and nearly always based on a single, typically binary, behavioural metric for a conditioned response. This is unfortunate for several reasons. Foremost, it has become increasingly apparent that invertebrates exhibit inter-individual differences in many aspects of their behaviour, and also that the conditioned response probability for an animal group does not adequately represent the behaviour of individuals in classical conditioning. Furthermore, a binary response character cannot yield a graded score for each individual. We also hypothesise that due to the complexity of a conditioned response, a single metric need not reveal an individual's full learning potential. In this paper, we report individual learning scores for freely moving adult male crickets (Gryllus bimaculatus) based on a multi-factorial analysis of a conditioned response. First, in an absolute conditioning paradigm, we video-tracked the odour responses of animals that, in previous training, received either odour plus reward (sugar water), reward alone, or odour alone to identify behavioural predictors of a conditioned response. Measures of these predictors were then analysed using binary regression analysis to construct a variety of mathematical models that give a probability for each individual that it exhibited a conditioned response (Presp). Using standard procedures to compare model accuracy, we identified the strongest model which could reliably discriminate between the different odour responses. Finally, in a differential appetitive olfactory paradigm, we employed the model after training to calculate the Presp of animals to a conditioned, and to an unconditioned odour, and from the difference a learning index for each animal. Comparing the results from our multi-factor model with a single metric analysis (head bobbing in response to a conditioned odour), revealed advantageous aspects of the model. A broad distribution of model-learning scores, with modes at low and high values, support the notion of a high degree of variation in learning capacity, which we discuss.

Behavioural Strategies in Cyclic Models: The Effects of Directional Movement Tactics

We investigate behavioural strategies in stochastic simulations of systems with cyclic nonhierarchical dominance, as ageneralisation of the rock-paper-scissors game. We introduce directional movement tactics to one out of the species, whose individuals move according to an innate or a conditioned response to a stimulus; individuals of the other species move randomly. The directional movement tactics allow the individuals to conquer or maintain territory, either attacking or anticipating or Safeguarding themselves. We study the effects of the behavioural strategies for individuals with different levels of perception of the neighbourhood. Besides, we investigate the case where not all individuals are conditioned to perform the behavioural strategy or where individuals that do not use the tactic for every move. We found that self-preservation behaviour is more profitable in terms of population growth, where the best result is achieved for individuals with large perception radius that always move according to the movement tactic. Our findings show that the attack tactics is more gainful for short perception radius and if the individuals alternate the tactic with random movement. For anticipation, the best result is achieved for individuals with long-range perception using the tactics rarely. Finally, we calculated the coexistence probability and found that, in addition to providing a greater spatial density for the species, the Safeguarding tactic is the least jeopardising to biodiversity. Our results may be useful for experimental and theoretical biologists to understand systems of species whose individuals behave strategically, and how coexistence is maintained in an uneven scenario.

A new model for recovery-from-extinction effects in Pavlovian conditioning and exposure therapy

Exposure therapy is an effective intervention for anxiety-related problems. A mechanism of this intervention has been the extinction procedure in Pavlovian conditioning, and their findings have provided many effective intervention strategies that can promote the effect of and prevent relapse following exposure sessions. However, traditional associative theories that have explained Pavlovian conditioning cannot comprehensively explain their findings. In particular, it was difficult to explain the recovery-from-extinction effects, which is the reappearance of conditioned response following extinction. In this study, we propose a new associative model that can deal with procedures that promote an effect of extinction and many recovery-from-extinction effects. The cores of this model are that the asymptotic strength of the inhibitory association depends on the degree of excitatory association retrieved in a context in which CS is presented and that the retrieval is determined by the similarity between contexts during reinforcement and non-reinforcement and the present context. Moreover, this model assumes that these similarities change under specific conditions. By adding these assumptions to the traditional framework, many difficulties in explaining these phenomena can be resolved. Our model can provide not only a new perspective in associative learning, but also many implications for exposure therapy.

Beyond the classic extinction network: a wider, comparative view

Extinction learning modifies the dynamics of brain circuits such that a previously learned conditioned response is no longer generated. The majority of extinction studies use fear conditioning in rodents and identified the prefrontal cortex, the hippocampus, and the amygdala as core regions of the extinction circuit. We sought to find answers to two questions: First, do we find a similar functional brain circuit in birds, which underwent a 300-million-year separate evolution from mammals? Second, do we have to incorporate the cerebellum as a key component of the central extinction circuit? We indeed show that the avian extinction pathways are not identical but highly similar to those of mammals. In addition, we reveal that the human cerebellum processes prediction errors, a key element driving extinction of learned fear responses, and contributes to context-related effects of extinction.