Eyeblink classical conditioning and BOLD fMRI of anesthesia-induced changes in the developing brain
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Updated: Mar 15, 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
Daniil P Aksenov1, Michael J Miller1, Limin Li1
1NorthShore University HealthSystem, Evanston, IL, 60201, USA.
Insights
Infant anesthesia exposure may impair brain development. Studies show anesthesia in young rabbits reduced functional brain responses related to learning and memory, suggesting long-term impacts on neuronal plasticity.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Anesthesiology
Background:
- General anesthesia is common in children, with emerging concerns about long-term effects on neuronal development.
- Previous research indicates anesthesia exposure in infancy can lead to learning and memory deficits.
- The functional consequences of early anesthesia exposure on brain activity remain largely unexamined.
Purpose of the Study:
- To investigate the functional brain changes associated with early-life anesthesia exposure.
- To compare the functional magnetic resonance imaging (fMRI) responses in adult rabbits exposed to anesthesia as infants versus unanesthetized controls.
- To examine how learning a classical conditioning task affects brain function in these groups.
Main Methods:
- Utilized Blood-Oxygen-Level-Dependent (BOLD) functional magnetic resonance imaging (fMRI) in awake rabbits.
- Measured functional brain responses in the whisker barrel cortex before and after a trace eyeblink classical conditioning paradigm.
- Compared functional changes (activated volume and time course) between rabbits exposed to isoflurane anesthesia during infancy and unanesthetized controls.
Main Results:
- Both groups showed a reduced duration of BOLD response after learning.
- Rabbits exposed to infant anesthesia exhibited a decreased BOLD response volume in the whisker barrel cortex.
- This volume reduction was particularly pronounced in the deeper infragranular layer of the cortex.
Conclusions:
- Early-life anesthesia exposure may alter intracortical processes crucial for learning-related brain plasticity.
- Functional changes in the brain following early anesthesia may persist into young adulthood.
- These findings highlight potential long-term neurological consequences of infant anesthesia.
Abstract:
Millions of children undergo general anesthesia each year in the USA alone, and a growing body of literature from animals and humans suggests that exposure to anesthesia at an early age can impact neuronal development, leading to learning and memory impairments later in childhood. Although a number of studies have reported behavioral and structural effects of anesthesia exposure during infancy, the functional manifestation of these changes has not been previous examined. In this study we used BOLD fMRI to measure the functional response to stimulation in the whisker barrel cortex of awake rabbits before and after learning a trace eyeblink classical conditioning paradigm. The functional changes, in terms of activated volume and time course, in rabbits exposed to isoflurane anesthesia during infancy was compared to unanesthetized controls when both groups reached young adulthood. Our findings show that whereas both groups exhibited decreased BOLD response duration after learning, the anesthesia-exposed group also showed a decrease in BOLD response volume in the whisker barrel cortex, particularly in the deeper infragranular layer. These results suggest that anesthesia exposure during infancy may affect the intracortical processes that mediate learning-related plasticity.

