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Updated: May 11, 2026

The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
Rehabilitation training using complex motor learning rescues deficits in eyeblink classical conditioning in female
Jennifer L Wagner1, Anna Y Klintsova, William T Greenough
1Department of Psychology , Indiana University Purdue University Indianapolis, Indianapolis, Indiana.
Insights
Rehabilitation training using complex motor learning improved eyeblink conditioning in female rats exposed to alcohol, suggesting potential therapies for fetal alcohol spectrum disorders (FASD). This approach may help ameliorate cognitive and behavioral deficits in children with FASD.
Area of Science:
- Neuroscience
- Developmental Psychology
- Translational Medicine
Background:
- Fetal alcohol spectrum disorders (FASD) present significant behavioral and cognitive challenges in children, with limited effective treatments.
- Neonatal alcohol exposure in rats models human third-trimester brain development, causing cerebellar damage and impaired eyeblink conditioning.
- These deficits in the animal model predict similar impairments observed in children with FASD, highlighting its translational value.
Purpose of the Study:
- To investigate if complex motor learning rehabilitation can mitigate cerebellar-dependent eyeblink conditioning deficits caused by neonatal alcohol exposure.
- To extend translational research by assessing the efficacy of motor learning interventions in an established FASD animal model.
Main Methods:
- Rats exposed to binge-like alcohol during development underwent 20 days of obstacle course training (complex motor learning).
- The impact of this rehabilitation on eyeblink classical conditioning was assessed.
- Previous work confirmed this training enhances cerebellar synaptic plasticity and motor coordination.
Main Results:
- Rehabilitation training significantly reduced alcohol-induced deficits in acquiring eyeblink conditioning in female rats.
- No significant improvement was observed in male rats following the same rehabilitation.
- Results suggest a normalization of cerebellar-dependent learning in alcohol-exposed females.
Conclusions:
- Complex motor learning rehabilitation shows promise for ameliorating functional impairments in adolescents with FASD, particularly those linked to cerebellar damage.
- Eyeblink classical conditioning deficits in children with FASD are well-documented and can serve as a metric for evaluating interventions like motor learning.
- These findings support the development of targeted rehabilitation strategies for FASD.
Background:
Effective treatments for the behavioral and cognitive deficits in children with fetal alcohol spectrum disorders (FASD) are lacking, and translational approaches using animal models can help develop rational interventions. One such model, binge-like alcohol exposure in neonatal rats during the period of brain development comparable with that of the human third trimester, causes structural and functional damage to the cerebellum and disrupts cerebellar-dependent eyeblink classical conditioning. The eyeblink conditioning deficits first demonstrated in this rat model predicted the similar deficits subsequently demonstrated in children with FASD.
Methods:
The current study extends this translational approach by testing the hypothesis that rehabilitation training involving 20 days of training on traversal of an obstacle course (complex motor learning) would ameliorate the deficits on classical conditioning of eyeblink responses produced by the neonatal alcohol exposure. We have previously shown that this training stimulates cerebellar synaptic plasticity and improves alcohol-induced deficits on motor coordination tasks.
Results:
The current studies found that rehabilitation training significantly attenuated alcohol-induced deficits in acquisition of eyeblink conditioning in females but not in males. These results are consistent with normalization of cerebellar-dependent learning, at least in alcohol-exposed females.
Conclusions:
These findings extend previous studies in this model suggesting that rehabilitation of adolescents with FASD using training with complex motor learning tasks could be effective in ameliorating functional impairments associated with cerebellar damage. Eyeblink classical conditioning deficits are now well documented in children with FASD and could serve as an evaluation measure to continue to develop therapeutic interventions such as complex motor learning.

