Abstracts

Rationale: Somatostatin positive GABAergic interneurons in the CA1 oriens layer with axons projecting to the lacunosum moleculare (O-LM cells) are thought to play key roles in the behavioral state-dependent regulation of the temporo-ammonic entorhinal input to hippocampal CA1 pyramidal cells. Importantly, O-LM cells are selectively vulnerable in animal models of temporal lobe epilepsy (TLE), likely contributing to the robust hyperexcitability observed following activation of the temporo-ammonic inputs to CA1. The decrease in feed-back distal dendritic inhibition in the lacunosum moleculare caused by the dysfunction and partial loss of O-LM cells may contribute to seizure propagation and cognitive deficits in epileptic patients. However, there is an absence of information about the behavior and function of O-LM cells in the awake, non-anesthetized brain, significantly limiting our understanding of the gating of the entorhino-hippocampal interactions during physiological and pathological hippocampal network functions.Methods: In order to record the activity of O-LM cells in awake animals, we performed juxtacellular recordings of post-hoc identified O-LM cells in vivo in head-fixed control adult mice that can rest or run on a spherical treadmill. The identity of the O-LM cells was determined using biocytin-based visualization of the axonal and dendritic arbors and by immunocytochemistry for interneuronal markers. Results: Our results show that successful recordings and post-hoc recovery and identification of O-LM cells could be achieved in the awake mice using the juxtacellular technique. O-LM cells displayed extensive axonal arborization in the LM layer with the axonal cloud restricted to CA1. O-LM interneurons showed immunoreactivity for somatostatin in the cell body and mGluR1a in the somato-dendritic region. Similar to what has been reported in anesthetized rats, O-LM cells fired preferentially during the troughs of the theta oscillations. However, O-LM cells showed dramatic alterations in their firing rates during running compared to stationary periods. Conclusions: On-going research is aimed at determining the timing of GABA release from O-LM cells into the distal dendritic regions of CA1 pyramidal cells during behaviorally relevant theta, gamma, and ripple oscillations in control and epileptic animals. This project was funded by the Epilepsy Foundation (C.V.), and by the NIH KO8NS056210 (P.G.) and NS35915 (I.S.).