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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
Dose-dependent deficits in dual interstimulus interval classical eyeblink conditioning tasks following neonatal binge
Kevin L Brown1, Lyngine H Calizo, Mark E Stanton
1Department of Psychology, University of Delaware, Newark, Delaware, USA. kbrown@psych.udel.edu
Insights
Neonatal alcohol exposure in rats impairs eyeblink conditioning (EBC) in a dose-dependent manner. Moderate alcohol doses reveal subtle EBC deficits, suggesting EBC
Area of Science:
- Neuroscience
- Developmental Psychology
- Toxicology
Background:
- Neonatal alcohol exposure in rats models human fetal alcohol spectrum disorders (FASD).
- Previous studies show cerebellar damage and impaired classical eyeblink conditioning (EBC) with high alcohol doses (≥5 g/kg/day) during postnatal days (PD) 4-9.
- This study investigates EBC deficits at lower alcohol doses (3-5 g/kg/day) during the same critical developmental window.
Purpose of the Study:
- To determine if lower doses of neonatal alcohol exposure (3-5 g/kg/day) induce deficits in classical eyeblink conditioning (EBC).
- To identify specific EBC timing and acquisition impairments resulting from moderate neonatal alcohol exposure.
- To evaluate the utility of ISI discrimination tasks for detecting alcohol-induced EBC deficits.
Main Methods:
- Five groups of neonatal rats received either no intervention, sham intubation, or alcohol (3, 4, or 5 g/kg/day) via intubation on PD4-9.
- Adult rats were trained on EBC tasks involving either ISI discrimination or temporal uncertainty.
- Conditioned response (CR) acquisition, onset, peak, and latency were analyzed.
Main Results:
- Alcohol exposure impaired CR acquisition in a dose- and task-dependent manner.
- Higher doses (4 and 5 g/kg/day) impaired CR acquisition in both EBC tasks, particularly in peak amplitude.
- A moderate dose (3 g/kg/day) impaired CR acquisition only in the ISI discrimination task, with later CR onset and peak observed in some conditions.
Conclusions:
- ISI discrimination is sensitive to detecting CR deficits from moderate neonatal alcohol exposure.
- This EBC paradigm may aid in the early identification and diagnosis of individuals with FASD.
- Findings highlight the impact of moderate alcohol exposure on cerebellar-dependent learning and timing.
Background:
Neonatal alcohol consumption in rats is widely used to model cerebellar injury arising from 3rd-trimester human fetal alcohol exposure. Binge alcohol exposure of 5 g/kg/day or more over postnatal days (PD) 4 to 9 in rats damages the cerebellum and consequently impairs classical eyeblink conditioning (EBC). The present study sought to identify deficits in EBC using doses lower than those that have been reported previously following alcohol exposure limited to PD4-9. Complex conditioned response (CR) timing tasks utilizing 2 interstimulus intervals (ISIs) were used to test the hypothesis that 3 g/kg/day of alcohol would produce early onset and early peaked CRs, whereas 4 and 5 g/kg/day would impair CR acquisition.
Methods:
Five neonatal treatment groups were used: (1) undisturbed controls, (2) sham intubation controls, (3) 3 g/kg/day of alcohol, (4) 4 g/kg/day of alcohol, or (5) 5 g/kg/day of alcohol. Intubations occurred over PD4-9. In adulthood, rats were trained using ISI discrimination (Experiment 1) or temporal uncertainty (Experiment 2) EBC tasks. In ISI discrimination, 2 distinct conditioned stimuli (CSs; tone and light) are reinforced with a periocular shock unconditioned stimulus (US) at 2 different CS-US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both CS-US intervals.
Results:
Alcohol-exposed subjects were impaired in CR acquisition in a task- and dose-dependent fashion. CR deficits were most salient in the peak amplitude measure and occurred in both tasks following alcohol exposure at 4 and 5 g/kg/day. Alcohol at a dosage of 3 g/kg/day impaired CR acquisition only in ISI discrimination. All alcohol doses failed to produce short latency CRs in either task. Alcohol-exposed subjects displayed later-onset and later-peaked CRs to the long-ISI CS in ISI discrimination relative to controls.
Conclusions:
ISI discrimination training may be ideal to identify CR deficits resulting from neonatal exposure to moderate alcohol doses. Applications of this EBC task to humans may enable reliable early identification and diagnosis of individuals with fetal alcohol spectrum disorders.
