Naturalistic stimulus trains evoke reproducible subicular responses both within and between animals in vivo

Previous investigation of CA1-evoked subicular responses has used either single low-frequency pulses (LF), paired-pulses (PP), or high-frequency bursts. Here we test for the first time how subiculum responds to naturalistic stimulation trains (NSTs). We recorded CA1-evoked field potentials from dorsal rat subiculum in response to LF, PP, and two NST patterns. The latter were derived from CA1 place cell activity; NST1 contained bursts of stimuli presented in two main episodes, while the burst-patterned stimuli in NST2 were spaced more evenly. NSTs generated significantly greater field responses compared with LF or PP patterns. Response patterns to either NST were significantly correlated across trial repeats in 9 out of 10 rats, supporting a robust postsynaptic encoding of CA1 input by subiculum. Correlations between NST responses were also observed across experiments; however, these were more variable than those within experiments. The relationship between response magnitude and activation history revealed a strong correlation between magnitude and NST instantaneous frequency for NST1 but was weaker for NST2. In addition, the number of stimuli within a prior 500 ms window was a determining factor for response magnitude for both NSTs. Overall, the robust reproducibility in subicular responses within rats suggests that information within NSTs is faithfully transmitted through the CA1-subiculum axis. However, variation in response sequences across rats suggests that encoding patterns to the same input differ across the subiculum. Changes in the ratio of target bursting and regularly spiking neurons along the subicular proximodistal axis may account for this variation. The activation history of this connection also appears to be a strong determining factor for response magnitude.