Effects of Developmental Alcohol Exposure on Associative Memory and the Medial Prefrontal Cortex-Reuniens-Hippocampus Circuit in a Rodent Model of Fetal Alcohol Spectrum Disorders
Date
2022-05
Authors
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Publisher
University of Delaware
Abstract
Fetal Alcohol Spectrum Disorders (FASD) is an array of developmental disorders defined
by physical, behavioral, and cognitive deficits as the result of prenatal exposure to alcohol. As
many as 1 in 20 live births in the United States have been exposed to sufficient alcohol exposure
(AE) to produce lasting, significant impairments in these areas. Among these deficits, a notable
effect of AE is the damage seen to executive function (EF), a set of cognitive controls involved
in goal-directed behaviors. EF regulation has been associated with activity in both the
hippocampus (HPC) and medial prefrontal cortex (mPFC) in the mammalian brain. However, an
intermediary structure, the nucleus reuniens (Re) has been shown to facilitate communication
between the HPC and mPFC. Research has demonstrated that developmental AE can specifically
damage the Re, compromising communication between structures. It is therefore hypothesized
that damage to the structural integrity of the mPFC-Re-HPC circuit is linked to the EF deficits
observed in FASD by compromising the synchrony between the mPFC and HPC.
This study used a rodent model of third trimester binge alcohol exposure to examine the
behavioral and neuroanatomical alterations to the Re that result from neonatal AE. In the present
study an Object-in-Place (OIP) associative memory task was used as a measure of interaction
between the hippocampus and medial prefrontal cortices.
In addition to behavioral data, the expression of protein cFos, the product of the
immediate early gene cFos, a marker of neuronal activation was quantified in the Re. An
impairment of associative memory formation in AE rats, mirrored by a decrease in cFos
expression in the Re were expected as a result of exposure to alcohol.
No significant effect of postnatal treatment was found on memory formation between
sample and test phases. However, a significant improvement in female performance between sample and test phases was found regardless of postnatal treatment. Additionally, no significant
effect was found on the number of cFos-positive cells within the Re, indicating that the
activation of the Re neurons was not compromised during this task. This study is important in
examining what mechanistic alterations are related to AE and how they are involved in deficits
associated with FASD.
Description
Keywords
Fetal alcohol spectrum disorders, Alcohol exposure, Memory formation