scholarly journals Pigs as a new behavioral model for studying Pavlovian eyeblink conditioning

2021 ◽  
Author(s):  
Henk-Jan Boele ◽  
Sangyun Joung ◽  
Joanne Fil ◽  
Austin T Mudd ◽  
Stephen A Fleming ◽  
...  
Keyword(s):  
Eyeblink Conditioning ◽  
Unconditional Stimulus ◽  
Preclinical Model ◽  
Peak Time ◽  
Intact Male ◽  
Delay Conditioning ◽  
Conditioning Paradigm ◽  
Association Learning ◽  
Young Pigs ◽  
The Moment

Intro: Pigs have been an increasingly popular preclinical model in nutritional neuroscience, as their anatomy, physiology, and nutrition requirements are highly comparable to those of humans. Eyeblink conditioning is one of the most well-validated behavioral paradigms in neuroscience to study underlying mechanisms of learning and memory formation in the cerebellum. Eyeblink conditioning has been performed in many species but has never been done on young pigs. Therefore, our aim here was to develop and validate an eyeblink conditioning paradigm in young pigs. Method: Eighteen intact male pigs were artificially reared from postnatal day 2 to 30. The eyeblink conditioning setup consisted of a sound-damping box with a hammock that pigs were placed in, which allowed the pig to remain comfortable yet maintain a typical range of head motion. In a delay conditioning paradigm, the conditional stimulus (CS) was a 550 ms blue light-emitting diode (LED), the unconditional stimulus (US) was a 50 ms eye air-puff, the CS-US interval was 500 ms. Starting at postnatal day 14, pigs were habituated for five days to the eyeblink conditioning setup, followed by 5 daily sessions of acquisition training (40 paired CS-US trials each day). Results: The group-averaged amplitude of eyelid responses gradually increased over the course of the five days of training, indicating that pigs learned to make the association between the LED light CS and the air-puff US. A similar increase was found for the conditioned response (CR) probability: the group-averaged CR probability on session 1 was about 12% and reached a CR probability of 55% on day 5. The latency to CR peak time lacked a temporal preference in the first session, but clearly showed preference from the moment that animals started to show more CRs in session 2 and onwards whereby the eyelid was maximally closed exactly at the moment that the US would be delivered. Conclusion: We concluded that 4-week-old pigs have the capability of performing in a cerebellar classical association learning task, demonstrating for the first time that eyeblink conditioning in young pigs has the potential to be a valuable behavioral tool to measure neurodevelopment.

scholarly journals Young Domestic Pigs (Sus scrofa) Can Perform Pavlovian Eyeblink Conditioning

2021 ◽  
Vol 15 ◽  
Author(s):  
Henk-Jan Boele ◽  
Sangyun Joung ◽  
Joanne E. Fil ◽  
Austin T. Mudd ◽  
Stephen A. Fleming ◽  
...  
Keyword(s):  
Light Emitting Diode ◽  
Eyeblink Conditioning ◽  
Unconditional Stimulus ◽  
Preclinical Model ◽  
Peak Time ◽  
Intact Male ◽  
Delay Conditioning ◽  
Conditioning Paradigm ◽  
Young Pigs ◽  
The Moment

Introduction: Pigs have been an increasingly popular preclinical model in nutritional neuroscience, as their anatomy, physiology, and nutrition requirements are highly comparable to those of humans. Eyeblink conditioning is one of the most well-validated behavioral paradigms in neuroscience to study underlying mechanisms of learning and memory formation in the cerebellum. Eyeblink conditioning has been performed in many species but has never been done on young pigs. Therefore, our aim here was to develop and validate an eyeblink conditioning paradigm in young pigs.Method: Eighteen intact male pigs were artificially reared from postnatal day 2–30. The eyeblink conditioning setup consisted of a sound-damping box with a hammock that pigs were placed in, which allowed the pig to remain comfortable yet maintain a typical range of head motion. In a delay conditioning paradigm, the conditional stimulus (CS) was a 550 ms blue light-emitting diode (LED), the unconditional stimulus (US) was a 50 ms eye air-puff, the CS-US interval was 500 ms. Starting at postnatal day 14, pigs were habituated for 5 days to the eyeblink conditioning setup, followed by 5 daily sessions of acquisition training (40 paired CS-US trials each day).Results: The group-averaged amplitude of conditioned eyelid responses gradually increased over the course of the 5 days of training, indicating that pigs learned to make the association between the LED light CS and the air-puff US. A similar increase was found for the conditioned response (CR) probability: the group-averaged CR probability on session 1 was about 12% and reached a CR probability of 55% on day 5. The latency to CR peak time lacked a temporal preference in the first session but clearly showed preference from the moment that animals started to show more CRs in session 2 and onwards whereby the eyelid was maximally closed exactly at the moment that the US would be delivered.Conclusion: We concluded that 3-week-old pigs have the capability of performing in a cerebellar classical conditioning task, demonstrating for the first time that eyeblink conditioning in young pigs has the potential to be a valuable behavioral tool to measure neurodevelopment.

Subclinical cerebellar dysfunction in patients with migraine: Evidence from eyeblink conditioning

Cephalalgia ◽  
2014 ◽  
Vol 34 (11) ◽  
pp. 904-913 ◽  
Author(s):  
Marcus Gerwig ◽  
Lisa Rauschen ◽  
Charly Gaul ◽  
Zaza Katsarava ◽  
Dagmar Timmann
Keyword(s):  
Primary Outcome ◽  
Eyeblink Conditioning ◽  
Primary Outcome Measure ◽  
Clinical Findings ◽  
Secondary Outcome ◽  
Cerebellar Dysfunction ◽  
Conditioned Eyeblink ◽  
Delay Conditioning ◽  
Conditioning Paradigm ◽  
Female Patients

Background Clinical findings suggest cerebellar dysfunction in patients with migraine. Eyeblink classical conditioning (EBCC) is a simple form of associative learning which depends on the integrity of the cerebellum. The aim of this study was to assess whether EBCC is disturbed in patients with migraine. Methods A delay conditioning paradigm was used in the headache-free interval in 32 female patients with migraine, in 24 of them without (MwoA) and eight with aura (MwA), and in 32 age-matched female controls. As primary outcome measure acquisition and as secondary outcome measures timing and extinction of conditioned eyeblink responses (CR) were assessed. Results CR acquisition was significantly reduced in all migraine patients (mean total CR incidence 35.2 ± 22.1%) compared to controls (54.7 ± 21.3%; p < 0.001; Bonferroni-corrected p level < 0.025) and in MwA patients (19.9 ± 20.2%) compared to matched controls (58.2 ± 27.0%; p = 0.006) but not in MwoA patients (40.3 ± 20.6%) compared to matched controls (53.6 ± 19.7%; p = 0.028; Bonferroni-corrected p level < 0.0166). Decrease of CR incidences in MwA patients was not significantly different compared to MwoA patients ( p = 0.021; Bonferroni-corrected p level < 0.0166). CR timing and extinction was not affected in migraine patients. Conclusions Reduced acquisition of CRs in the cohort of female patients studied here supports findings of a cerebellar dysfunction in migraine.

scholarly journals Active Inference and Learning in the Cerebellum

2016 ◽  
Vol 28 (9) ◽  
pp. 1812-1839 ◽  
Author(s):  
Karl Friston ◽  
Ivan Herreros
Keyword(s):  
Eyeblink Conditioning ◽  
Predictive Coding ◽  
Trace Conditioning ◽  
Face Validity ◽  
Active Inference ◽  
Focal Lesions ◽  
Delay Conditioning ◽  
Neuronal Populations ◽  
Intrinsic Connectivity ◽  
The Face

This letter offers a computational account of Pavlovian conditioning in the cerebellum based on active inference and predictive coding. Using eyeblink conditioning as a canonical paradigm, we formulate a minimal generative model that can account for spontaneous blinking, startle responses, and (delay or trace) conditioning. We then establish the face validity of the model using simulated responses to unconditioned and conditioned stimuli to reproduce the sorts of behavior that are observed empirically. The scheme’s anatomical validity is then addressed by associating variables in the predictive coding scheme with nuclei and neuronal populations to match the (extrinsic and intrinsic) connectivity of the cerebellar (eyeblink conditioning) system. Finally, we try to establish predictive validity by reproducing selective failures of delay conditioning, trace conditioning, and extinction using (simulated and reversible) focal lesions. Although rather metaphorical, the ensuing scheme can account for a remarkable range of anatomical and neurophysiological aspects of cerebellar circuitry—and the specificity of lesion-deficit mappings that have been established experimentally. From a computational perspective, this work shows how conditioning or learning can be formulated in terms of minimizing variational free energy (or maximizing Bayesian model evidence) using exactly the same principles that underlie predictive coding in perception.

scholarly journals Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

2015 ◽  
Vol 112 (45) ◽  
pp. 14060-14065 ◽  
Author(s):  
Anders Rasmussen ◽  
Riccardo Zucca ◽  
Fredrik Johansson ◽  
Dan-Anders Jirenhed ◽  
Germund Hesslow
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Compound Stimulus ◽  
Eyeblink Conditioning ◽  
Unconditional Stimulus ◽  
Cell Activity ◽  
Neural Mechanisms ◽  
Wagner Model ◽  
Central Tenet ◽  
Reinforcement Value

A central tenet of Rescorla and Wagner’s model of associative learning is that the reinforcement value of a paired trial diminishes as the associative strength between the presented stimuli increases. Despite its fundamental importance to behavioral sciences, the neural mechanisms underlying the model have not been fully explored. Here, we present findings that, taken together, can explain why a stronger association leads to a reduced reinforcement value, within the context of eyeblink conditioning. Specifically, we show that learned pause responses in Purkinje cells, which trigger adaptively timed conditioned eyeblinks, suppress the unconditional stimulus (US) signal in a graded manner. Furthermore, by examining how Purkinje cells respond to two distinct conditional stimuli and to a compound stimulus, we provide evidence that could potentially help explain the somewhat counterintuitive overexpectation phenomenon, which was derived from the Rescorla–Wagner model.

scholarly journals Some indices of GSR activity in a long-delay conditioning paradigm

1966 ◽  
Vol 4 (6) ◽  
pp. 207-208 ◽  
Author(s):  
Robert D. Hare ◽  
Terence D. Creighton ◽  
Lynn Hunt
Keyword(s):  
Delay Conditioning ◽  
Conditioning Paradigm

scholarly journals Enhanced Acquisition and Retention of Conditioned Eyeblink Responses in Veterans Expressing PTSD Symptoms: Modulation by Lifetime History of Mild Traumatic Brain Injury

2020 ◽  
Vol 14 ◽  
Author(s):  
Justin D. Handy ◽  
W. Geoffrey Wright ◽  
Amanda Haskell ◽  
Labeeby Servatius ◽  
Richard J. Servatius
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Eyeblink Conditioning ◽  
Unconditional Stimulus ◽  
Ptsd Symptoms ◽  
Conditioned Eyeblink ◽  
Enhanced Sensitivity ◽  
Conditioned Responses ◽  
The Impact

Enhanced acquisition of eyeblink conditioning is observed in active duty military and veterans expressing PTSD symptoms (PTSD+) and those expressing temperamental vulnerabilities to develop PTSD after traumatic experiences, such as behaviorally inhibited temperament. There is a growing literature showing persistent cerebellar abnormalities in those experiencing mild traumatic brain injury (mTBI+) as well as linkages between mTBI and PTSD. With the dependency of eyeblink conditioning on cerebellar processes, the impact of mTBI on eyeblink conditioning in veterans expressing PTSD is unknown. The present study assessed eyeblink conditioning in veterans during two sessions separated by 1 week. With a focus on the accelerated learning of veterans expressing PTSD, training utilized a protocol which degrades learning through interspersing conditioned stimulus (CS) exposures amongst delay-type trials of CS and unconditional stimulus (US) co-terminating trials. Faster acquisition of the eyeblink conditioned responses (CR) was observed in PTSD during Week 1. The Week 2 assessment revealed an interaction of mTBI and PTSD, such that asymptotic performance of PTSD+ was greater than PTSD− among mTBI− veterans, whereas these groups did not differ in mTBI+ veterans. To further examine the relationship between enhanced sensitivity to acquire eyeblink conditioning and PTSD, cluster analysis was performed based on performance across training sessions. Those with enhanced sensitivity to acquire eyeblink conditioned responses expressed more PTSD symptoms, which were specific to Cluster C symptoms of avoidance, in addition to greater behavioral inhibition. These results support the continued investigation of the conditioned eyeblink response as a behavioral indicator of stress-related psychopathology.

scholarly journals Cortical processing of breathing perceptions in the athletic brain

2017 ◽  
Author(s):  
Olivia K. Faull ◽  
Pete J. Cox ◽  
Kyle T. S. Pattinson
Keyword(s):  
Brain Activity ◽  
Chronic Respiratory Disease ◽  
Endurance Athletes ◽  
7 Tesla ◽  
Delay Conditioning ◽  
Conditioning Paradigm ◽  
Attention Networks ◽  
Primary Sensorimotor Cortex ◽  
Brain Processing ◽  
Future Work

AbstractAthletes regularly endure large increases in ventilation, and accompanying perceptions of breathlessness. While breathing perceptions often correlate poorly with objective measures of lung function in both health and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in endurance athletes, suggesting that athletes may be more accurate during respiratory interoception. To better understand the link between exercise and breathlessness, we sought to identify the mechanisms by which the brain processing of respiratory perception might be optimised in athletes.Twenty endurance athletes and 20 sedentary controls underwent 7 Tesla functional magnetic resonance imaging. Inspiratory resistive loading induced conscious breathing perceptions (breathlessness), and a delay-conditioning paradigm was employed to evoke preceding periods of anticipation. Athletes demonstrated anticipatory brain activity that positively correlated with resulting breathing perceptions within key interoceptive areas, such as the thalamus, insula and primary sensorimotor cortices, which was negatively correlated in sedentary controls. Athletes also exhibited greater connectivity between interoceptive attention networks and primary sensorimotor cortex. These functional differences in athletic brains suggest that exercise may optimise processing of respiratory sensations. Future work may probe whether these brain mechanisms are harnessed when exercise is employed to treat breathlessness within chronic respiratory disease.

scholarly journals Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Maryna Pilkiw ◽  
Nathan Insel ◽  
Younghua Cui ◽  
Caitlin Finney ◽  
Mark D Morrissey ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Eyeblink Conditioning ◽  
Conditioning Paradigm ◽  
Firing Rates ◽  
Neuron Ensemble ◽  
Transient Events ◽  
Trace Eyeblink Conditioning ◽  
Ensemble Activity ◽  
Conditioning Stimuli ◽  
Stimulus Environment

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.

scholarly journals Potential severity, mitigation, and control of Omicron waves depending on pre-existing immunity and immune evasion

2021 ◽  
Author(s):  
Ferenc A. Bartha ◽  
Péter Boldog ◽  
Attila Dénes ◽  
Tamás Tekeli ◽  
Zsolt Vizi ◽  
...  
Keyword(s):  
High Risk ◽  
Immune Evasion ◽  
Population Level ◽  
High Risk Population ◽  
Peak Time ◽  
Population Immunity ◽  
Reproduction Numbers ◽  
The Moment ◽  
And Control ◽  
Pharmaceutical Interventions

We assess the potential consequences of the upcoming SARS-CoV-2 waves caused by the Omicron variant. Our results suggest that even in those regions where the Delta variant is controlled at the moment by a combination of non-pharmaceutical interventions and population immunity, a significant Omicron wave can be expected. We stratify the population according to prior immunity status, and characterize the possible outbreaks depending on the population level of pre-existing immunity and the immune evasion capability of Omicron. We point out that two countries having similar effective reproduction numbers for the Delta variant can experience very different Omicron waves in terms of peak time, peak size and total number of infections among the high risk population.

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