Authors :
Presenting Author: Lijun (Reese) Guo, B.S. – Vanderbilt University
Salvatore Incontro, PhD – Vanderbilt University
Janaie Sandoval-Burnside, B.S., M.Sc. – Vanderbilt University
Colin Clark, B.S. (expected 2026) – Vanderbilt University
Miles Dryden, B.S. – Vanderbilt University
Simra Kazimuddin, B.S. – Vanderbilt University
Quynh Anh Nguyen, Ph.D. – Vanderbilt University
Rationale:
The fasciola cinereum (FC) is a small midline region at the posterior hippocampal tail, between CA1 and the third ventricle. It projects to multiple hippocampal-associated subregions, including CA1, CA2, and dentate gyrus, forming a conserved connectivity pattern (Park et al., 2022; Zouridis et al., 2024). However, FC has been largely omitted from canonical models of hippocampal circuitry. Recent work from our group challenges this view, showing that modulation of FC activity stops seizures in both mouse models and human patients with epilepsy (Jamiolkowski et al., 2024). This suggests FC helps stabilize networks by filtering inputs to regulate hippocampal excitability. Despite evidence of its functional relevance, its intrinsic neuronal properties remain poorly characterized. In vivo studies reported conflicting findings—Zouridis et al. (2024) observed CA1-like firing patterns in FC neurons, whereas Park et al. (2022) found reduced firing rates and hyperpolarized membrane potentials—hindering clarity on FC function. To address this discrepancy, we conducted ex vivo whole-cell recordings to systematically characterize intrinsic electrophysiological properties of FC excitatory neurons.
Methods:
Whole-cell patch-clamp recordings were performed on acute hippocampal slices from C57BL/6J mice (P21–P55). FC neurons were identified anatomically, and intrinsic membrane properties were measured under current- and voltage-clamp, including resting potential, input resistance, action potential threshold, AHP, and excitability.Results:
FC excitatory neurons segregated into two subtypes—G1 and G2—based on intrinsic firing profiles. G1 neurons exhibited regular spiking with low excitability, while G2 neurons displayed moderate excitability. Both subtypes fired fewer spikes than CA1 pyramidal neurons across increasing current steps, with G1 neurons consistently showing the lowest firing rates (Fig. 1D). G1 neurons had significantly higher rheobase, and both subtypes showed longer interspike intervals compared to CA1 (Fig. 1E–F), confirming lower intrinsic excitability.
Voltage-clamp recordings revealed significantly larger delayed rectifier K⁺ currents (Kv2.1-mediated) in G1 neurons compared to G2 (Fig. 2A–D). G1 neurons also exhibited greater M-current amplitudes (Kv7-mediated) than G2 (Fig. 2F–H). A positive correlation between Kv2.1 and M-current amplitudes (Fig. 2I) suggests a potential synergistic role in regulating excitability. Differential Kv2.1 and Kv7 channel function shapes excitability across FC subtypes.
Conclusions:
We resolve prior discrepancies in FC neuron excitability and establish FC as a physiologically distinct hippocampal subregion. Subtype-specific differences in intrinsic membrane properties, shaped by coordinated Kv2.1 and Kv7 channel activity, suggest that FC neurons exert local gating control over excitatory flow into the hippocampal circuit. These findings refine our understanding of FC excitatory neurons and highlight their specialized role within hippocampal circuit dynamics.
Funding:
NIH R00NS121399, Dept. of Pharmacology/Vanderbilt Brain Institute, Vanderbilt University