Sex-specific mechanisms underlie long-term potentiation at hippocampus-nucleus accumbens synapses.

Strengthening of Hipp-NAc synapses drives reward-related behaviors. Male and female mice have similar magnitudes of long-term potentiation (LTP) and both sexes have a predicted postsynaptic locus of plasticity. Despite these similarities, we illustrate here that sex-specific molecular mechanisms are used to elicit LTP. Given the bidirectional relationship between Hipp-NAc synaptic strength in mediating reward-related behaviors, the use of distinct molecular mechanisms may explain sex differences observed in stress susceptibility or response to rewarding stimuli. Discovery and characterization of convergent sex differences provides mechanistic insight into the sex-specific function of Hipp-NAc circuitry and has widespread implications for circuits mediating learning and reward-related behavior.