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Updated: Aug 7, 2026
Trace Fear Conditioning in Mice
Published on: March 21, 2014
Perinatal nutritional iron deficiency permanently impairs hippocampus-dependent trace fear conditioning in rats
Matthew D McEchron1, Alex Y Cheng, Heng Liu
1Department of Neural and Behavioral Science, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. mdm27@psu.edu
Insights
Perinatal iron deficiency (ID) impairs hippocampus-dependent learning in young rats. This developmental deficit persists even after nutritional correction, highlighting long-term impacts on cognitive function.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Iron deficiency (ID) in children is linked to impaired cognitive development.
- Developmental ID may negatively affect brain regions crucial for learning, like the hippocampus.
Purpose of the Study:
- To investigate the impact of perinatal nutritional iron deficiency on hippocampus-dependent learning in rats.
- To determine if this learning impairment is specific to hippocampus-dependent tasks and if it persists after nutritional intervention.
Main Methods:
- Rats were fed either an iron-deficient (ID) or control (CN) diet from 10 days before birth.
- Trace fear conditioning (hippocampus-dependent) and basic fear conditioning (non-hippocampus-dependent) were assessed on post-natal day (PND)-28.
- A separate group was switched from ID to CN diet on PND-31 and tested on PND-63.
Main Results:
- Perinatal ID significantly impaired trace fear conditioning in pups.
- ID pups did not show deficits in basic fear conditioning, suggesting specificity to hippocampus-dependent learning.
- Rats switched to a control diet on PND-31 still exhibited impaired trace fear conditioning in adulthood.
- Control tests indicated that motor deficits were not the cause of the learning impairments.
Conclusions:
- Developmental iron deficiency compromises hippocampus-dependent learning in rats.
- These learning deficits are specific to tasks requiring hippocampal function and are not solely due to motor impairments.
- Nutritional correction after PND-31 does not fully reverse the long-term effects of perinatal ID on hippocampus-dependent learning.
Abstract:
Many studies show that iron deficient (ID) children are at risk for poor cognitive development. This suggests that learning and cognitive centers in the brain, such as the hippocampus, may be compromised by developmental ID. The present study used a heart rate trace fear conditioning procedure in rats to show that perinatal nutritional ID impairs hippocampus-dependent learning. This procedure requires rats to associate a conditioned stimulus and a fearful unconditioned stimulus, which are separated by a trace interval. Rats were started on ID or control (CN) diets 10 days prior to birth, and learning was assessed on post natal day (PND)-28. The ID pups were impaired in trace fear coniditioning, but an ID control group was not impaired in a non-trace basic fear conditioning procedure that does not depend on the hippocampus. Another group was switched from ID to CN diet on PND-31, and this group also showed impairments in trace fear conditioning when tested during early adulthood (i.e. PND-63). Separate control tests show that ID may produce skeletal motor deficits. The ID-induced learning impairments in this study, however, were not due to altered motor activity because learning was assessed using non-motor heart rate responses.
