Alcohol Exposure During the Brain Growth Spurt Alters Medial Prefrontal Cortex Hippocampus Functional Connectivity During a Spatial Working Memory Task
Date
2023-05
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Publisher
University of Delaware
Abstract
The brain growth spurt is a period of rapid brain growth and development which occurs
during the third trimester of human pregnancy and the first two postnatal weeks in rodents. The
hippocampus and medial prefrontal cortex (mPFC), structures which are important for spatial
working memory, are vulnerable to alcohol exposure (AE) during the brain growth spurt. The
nucleus reuniens (RE) of the thalamus has been demonstrated to play a role in orchestrating
mPFC-hippocampus interactions which are necessary for spatial working memory. The RE has
also been shown to be damaged due to AE in a third trimester rodent model. Recently, our lab
has shown that rats exposed to alcohol during the brain growth spurt display spatial working
memory impairments. The current study examines mPFC-hippocampus theta synchrony to
determine if these effects can be explained by altered functional connectivity between these
regions.
In this study we measured mPFC-hippocampus theta coherence, a metric that describes
the degree to which mPFC-hippocampus theta rhythms are temporally correlated. We
hypothesized that rats exposed to alcohol during the brain growth spurt would show reduced
mPFC-hippocampus theta synchrony compared to sham intubated (SI) rats during decision
making. Specifically, we predicted that AE rats would show reduced theta coherence at the
choice point of a T-maze as they performed a spatial working memory task.
To study our hypothesis, pups were administered 5.25 g/kg/day alcohol via intragastric
intubation between postnatal days 4-9. The sham intubated (SI) group received intubation
without alcohol. Once rats reached adulthood (postnatal day 90), they completed pre-training in a
T-maze to become familiarized with the testing environment. Rats then underwent local field
potential (LFP) electrode implantation surgery, during which stainless steel wires were implanted
into the mPFC and hippocampus. Once recovered from surgery, rats were trained on the continuous alternation (CA) task, which is not a hippocampus dependent task but allowed rats to
learn the alternation rule. Upon reaching the choice accuracy criterion of 80% for two
consecutive days, rats learned the spatial working memory-dependent delayed alternation (DA)
task. Each DA session consisted of 10 second, 30 second, and 60 second delay trials, with 12
trials of each delay length in a pseudorandom sequence. LFPs were recorded as rats performed
the task. We then analyzed mPFC-hippocampus theta synchrony at the choice point of the T maze.
In support of our hypothesis that AE during the brain growth spurt reduces mPFC hippocampus theta synchrony, we found that DA task recording sessions of AE rats showed
lower mPFC-hippocampus theta coherence when rats occupied the maze choice point compared
to sessions of SI rats. Neural activity within brain regions was also altered, as hippocampus theta
power was increased in sessions from AE rats compared to sessions from SI rats. These findings
can help explain our previous finding of impaired spatial working memory in AE rodents. This
study is important because it contributes to filling the gap in knowledge of how developmental
AE affects cognitive function and the underlying mechanisms later in life.