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Whisker-signaled Eyeblink Classical Conditioning in Head-fixed Mice
Published on: March 30, 2016
Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism
Mark E Stanton1, Elizabeth Peloso, Kevin L Brown
1Department of Psychology, University of Delaware, Newark, DE 19716, USA. stanton@psych.udel.edu
Insights
Valproic acid (VPA) exposure in pregnant rats created an autism model. Offspring showed faster eyeblink conditioning, mirroring autistic children, but impaired reversal learning may not reflect autism.
Area of Science:
- Neuroscience
- Developmental Psychology
- Animal Models
Background:
- Valproic acid (VPA) exposure during gestation induces neurodevelopmental changes in offspring, serving as a model for autism spectrum disorder (ASD).
- Autistic individuals exhibit altered classical eyeblink conditioning and reversal learning, suggesting deficits in brainstem-cerebellar and prefrontal cortex circuitry.
Purpose of the Study:
- To investigate behavioral parallels between the VPA rodent model of autism and human autistic traits.
- To examine eyeblink conditioning and reversal learning in offspring exposed to VPA during gestation.
Main Methods:
- Pregnant Long-Evans rats received 600 mg/kg VPA on gestational day 12.
- Offspring were tested for discriminative eyeblink conditioning and reversal learning from postnatal day 26-31.
Main Results:
- VPA-exposed rats demonstrated accelerated eyeblink conditioning acquisition, aligning with findings in autistic children.
- VPA rats exhibited impaired reversal learning, potentially due to enhanced conditioning during acquisition rather than a true reversal deficit.
Conclusions:
- The VPA rodent model displays behavioral similarities to human autism, particularly in tasks engaging brainstem-cerebellar circuitry.
- Further research on eyeblink conditioning in autism and animal models is crucial for understanding the disorder's etiology.
Abstract:
Offspring of rats exposed to valproic acid (VPA) on gestational day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases . Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning and in reversal of instrumental discrimination learning . Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex. In order to explore behavioral parallels of the VPA rodent model with human autism, the present study exposed pregnant Long-Evans rats to 600 mg/kg VPA on GD12 and tested their offspring from Postnatal Day (PND26-31) on discriminative eyeblink conditioning and reversal. VPA rats showed faster eyeblink conditioning, consistent with studies in autistic children . This suggests that previously reported parallels between human autism and the VPA rodent model with respect to injury to brainstem-cerebellar circuitry are accompanied by behavioral parallels when a conditioning task engaging this circuitry is used. VPA rats also showed impaired reversal learning, but this likely reflected "carry-over" of enhanced conditioning during acquisition rather than a reversal learning deficit like that seen in human autism. Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder.

