Prenatal alcohol damages the subiculum, a key region for learning and memory: A narrative review

As an integral part of the hippocampal network, the subiculum (SUB) plays a critical role in learning, memory, and emotional processing. This region contains diverse neuronal populations with distinct projection patterns, each contributing uniquely to information processing. The SUB has also been implicated in several neuropathological conditions, including mood disorders and epilepsy, which are highly prevalent among individuals with fetal alcohol spectrum disorders. The objective of this review is to examine the potential involvement of the SUB, a key component of the hippocampal formation, in the cognitive and behavioral deficits associated with prenatal alcohol exposure (PAE). Clinical studies have shown that PAE is associated with reduced hippocampal formation volumes, including the SUB. Complementing these findings, preclinical models demonstrate that acute, binge-like alcohol exposure during the third-trimester equivalent period induces widespread apoptosis within the SUB. These early insults result in long-term consequences, including reduced neuronal density and altered physiological properties of surviving neurons later in life. Additionally, persistent alterations in SUB functional connectivity have been observed during memory recall tasks, such as contextual fear conditioning. Key questions remain regarding how PAE differentially affects the subdivisions of the SUB, how intrinsic subicular dysfunction influences broader neural network dynamics, and how these insights can be translated into effective therapeutic strategies for fetal alcohol spectrum disorders.