Selective damage of thalamic nucleus reuniens in a rat model of fetal alcohol spectrum disorders: alterations to hippocampus- and prefrontal cortex- dependent behaviors
Date
2018
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Individuals diagnosed with fetal alcohol spectrum disorders (FASD) often display behavioral impairments in executive functioning. Mechanistic studies have implicated coordination between prefrontal cortex and hippocampus (through thalamic nucleus reuniens) as critical for such executive functions. The current study characterized the neuroanatomical alterations to midline thalamus and alterations in executive function in a rodent model of fetal alcohol spectrum disorders. Alcohol diluted in milk formula was administered to Long Evans rat pups on postnatal days (PD) 4-9 (5.25 g/kg/day of ethanol, 11.9% v/v, intragastric intubation). Control animals were intubated without administration of liquid. In adulthood (PD72), brains of females were analyzed for total cell number and neuron number in three midline thalamic nuclei. Males from the same litters were run on a battery of behavioral assays in adulthood (postnatal day >55). This battery consisted of novel object recognition, object in place, spontaneous alternations, and behavioral flexibility tasks. Nucleus-specific damage was found in midline thalamus, resulting in long term loss of neurons as well as volume specifically in reuniens of alcohol-exposed females. Males demonstrated behavioral impairments in short-term spatial memory and rule-switching, but not object recognition or levels of activity, suggesting impairments in executive functioning. This constitutes the first investigation into the circuit-specific consequence of third trimester alcohol exposure on the midline thalamus. These specific neuroanatomical and behavioral alterations suggest that prenatal alcohol exposure results in damage to prefrontal-thalamo-hippocampal circuitry.