The Impacts of Early-life Adversity on Striatal and Hippocampal Memory Functions

The impacts of early-life adversity (ELA) on cognitive functions including striatal-dependent habit memory and hippocampal-dependent spatial memory were investigated in male mice. The ELA mouse model was generated via an altered cage environment with limited nesting and bedding materials during postnatal days 2-9 (P2-9). The altered cage environment affected the nesting behaviors of dams, creating a stressful condition for their offspring. The ELA mice had biased decision making and poor spatial memory when they grew into young adults (4-month-old). To explore the underlying synaptic basis of these effects, excitatory synapses represented by postsynaptic density protein-95 (PSD-95) were immunolabelled on a series of brain sections and stereologically quantified in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), as well as in area CA1 of the dorsal hippocampus. Increased PSD-95-immunoreactive synapses were observed in DLS but not DMS, whereas selective loss of PSD-95 synapses was detected in the stratum radiatum of area CA1. The spine data supported the selective effects of ELA on PSD-95 synapses. Specifically, both thin and mushroom-type spines were increased in DLS, while loss of thin spines was apparent in CA1 radiatum in ELA mice versus controls. The correlation between PSD-95 synapses and memory performances was further analyzed, and the data suggested that increased small (<0.20 μm³) and large (>0.40 μm³) synapses in DLS might drive ELA mice to make decisions largely relying on habit memory, while loss of small synapses in hippocampal CA1 damage the spatial memory of ELA mice.