Higher hyperpolarization activated current (Ih) in a subpopulation of hippocampal stratum oriens CA1 interneurons in Fragile X mice.

Fragile X syndrome is the most common inherited form of intellectual disability and the leading monogenetic cause of autism. Studies in mouse models of autism spectrum disorders, including the Fmr1 knockout (FX) mouse, suggest that an imbalance between excitation and inhibition in hippocampal circuits contributes to behavioral phenotypes. In addition to changes in excitatory and inhibitory synaptic transmission, changes in the intrinsic excitability of neurons can also contribute to circuit dysfunction. We and others previously identified changes in multiple voltage-gated ion channels in hippocampal excitatory pyramidal neurons in FX mice. Whether the intrinsic properties of hippocampal inhibitory interneurons are altered in FX remains largely unknown. We made whole-cell current clamp recordings from three types of interneurons in stratum oriens of the hippocampus: fast-spiking cells and two classes of low threshold spiking cells, oriens-lacunosum moleculare (OLM) and low-threshold high Ih (LTH) neurons. We found that in FX mice input resistance and action potential firing frequency were lower in LTH, but not FS or OLM, interneurons compared to wild type. LTH cell input resistance was not different between wild type and FX mice in the presence of the h-channel blocker ZD7288 suggesting a greater contribution of Ih in FX LTH cells. In agreement, we found using voltage clamp recording that Ih was higher in FX LTH cells compared to wild type. Our results suggest that the intrinsic excitability of LTH inhibitory interneurons contribute to altered excitatory/inhibitory balance in the hippocampus of FX mice. ### Competing Interest Statement The authors have declared no competing interest.