Prenatal alcohol exposure changes mouse brain circuitry involved in decision making

Prenatal alcohol exposure is a leading preventable cause of birth defects and neurodevelopmental abnormalities in the United States. It can lead to learning, memory, and impulsivity problems in both children and adults. In a new study conducted with mice, NIAAA scientists report that specific changes in a brain circuit involved in learning and decision making could underlie some of the behavioral effects of prenatal alcohol exposure. These findings by researchers in NIAAA’s Division of Intramural Clinical and Biological Research were published in Nature Communications.

In the study, the researchers exposed pregnant mice to alcohol and later tested the offspring’s cognitive function using two decision-making tasks—one focusing on goal-directed decisions (actions aimed at an outcome or consequence) and the other to probe decisions based on habits (actions resulting from frequent repetition without focus on a consequence). They found that offspring that had been prenatally exposed to alcohol had different decision-making strategies compared to those without prenatal exposure—prenatally exposed mice were more likely to rely on the cognitively demanding, goal-directed decision making at the expense of the less-demanding, habit-based decision making.

The researchers went on to measure electrical activity in the dorsal striatum—a brain region involved in learning and habit formation—as the offspring engaged in the decision-making tasks. They found that changes in two neurotransmitter systems—gamma-aminobutyric acid (GABA) and endocannabinoids—were associated with the observed differences in decision making in prenatally exposed animals. Specifically, the effects of endocannabinoids on neuron activity in the dorsal striatum increased while the levels of GABA decreased. GABA is the main inhibitory neurotransmitter in the brain. Endocannabinoids are chemicals produced within the brain that modulate the overactivity of neurons such as GABA and are involved in circuitry regulation associated with many brain functions. These findings suggest that treatments targeting the GABA and endocannabinoid systems might be useful in ameliorating impaired decision making associated with prenatal alcohol exposure.

Future research could help translate this work to humans, clarifying how much these changes in behavior and circuits translate to people with a history of prenatal alcohol exposure.

Reference:

Cuzon Carlson, V.C.; Gremel, C.M.; and Lovinger, D.M. Gestational alcohol exposure disrupts cognitive function and striatal circuits in adult offspring. Nature Communications 11:2555, 2020. PMID: 32444624