On 1 June 2026, Dr Yao-Ying Ma, Associate Professor in the Department of Biochemistry, Molecular Biology and Pharmacology at Indiana University School of Medicine, presented a seminar titled “Prenatal Alcohol Disrupts Reward Circuit Maturation”. The seminar focused on how early developmental insults shape synaptic organization within reward-related brain circuits and their long-term behavioral consequences.
A key focus of Dr Ma’s seminar was how prenatal alcohol exposure (PAE) disrupts the maturation of synaptic connectivity within the infralimbic cortex-nucleus accumbens pathway, a core component of the brain’s reward system. Using rodent models, she demonstrated that PAE accelerates the loss of silent synapses during early development, accompanied by a reduction in dendritic spine density within nucleus accumbens shell neurons. These structural changes reflect an abnormal trajectory of synaptic maturation, ultimately leading to altered excitatory circuit function.
Dr Ma further highlighted that PAE induces a persistent increase in calcium-permeable AMPA receptor (CP-AMPAR) recruitment at synapses in the nucleus accumbens shell. This shift in receptor composition destabilizes excitatory synaptic transmission and is associated with enhanced vulnerability to cocaine self-administration during adolescence. Together, these findings link early developmental exposure to alcohol with long-lasting modifications in reward circuit function and behavioral susceptibility to addiction.
In addition, Dr Ma presented mechanistic and intervention-based evidence showing that pharmacological blockade of CP-AMPARs, as well as circuit-specific optogenetic induction of long-term depression (LTD), can restore synaptic structure and normalize excitatory transmission. These results suggest that maladaptive synaptic remodeling following prenatal alcohol exposure is not irreversible and may be amenable to targeted circuit-level interventions.
In summary, the seminar emphasized aberrant synaptic maturation as a key mechanism connecting early-life environmental exposure to persistent dysfunction in reward circuitry. Dr Ma’s presentation provided important insights into how developmental perturbations can reshape neural circuit function and highlighted potential strategies for correcting these alterations at the synaptic level.