TY - JOUR T1 - Lack of hyper-inhibition of oriens-lacunosum moleculare cells by vasoactive intestinal peptide-expressing cells in a model of temporal lobe epilepsy JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0299-21.2021 SP - ENEURO.0299-21.2021 AU - Megan Wyeth AU - Paul S. Buckmaster Y1 - 2021/11/23 UR - http://www.eneuro.org/content/early/2021/11/23/ENEURO.0299-21.2021.abstract N2 - Temporal lobe epilepsy remains a common disorder with no cure and inadequate treatments, potentially due to an incomplete understanding of how seizures start. CA1 pyramidal cells and many inhibitory interneurons increase their firing rate in the seconds-minutes before a spontaneous seizure in epileptic rats. However, some interneurons fail to do so, including those identified as putative interneurons with somata in oriens and axons targeting lacunosum-moleculare (OLM cells). Somatostatin-containing cells, including OLM cells, are the primary target of inhibitory vasoactive intestinal polypeptide and calretinin-expressing (VIP/CR) bipolar interneuron-selective interneurons, type 3 (ISI-3). The objective of this study was to test the hypothesis that in epilepsy inhibition of OLM cells by ISI-3 is abnormally increased, potentially explaining the failure of OLM recruitment when needed most during the ramp up of activity preceding a seizure. Stereological quantification of VIP/CR cells in a model of temporal lobe epilepsy demonstrated that they survive in epileptic mice, despite a reduction in their somatostatin-expressing cell targets. Paired recordings of unitary inhibitory postsynaptic currents from ISI-3 to OLM cells did not show increased connection probability or increased connection strength, and failure rate was unchanged. When miniature postsynaptic currents in ISI-3 were compared, only mIPSC frequency was increased in epileptic hippocampi. Nevertheless, spontaneous and miniature postsynaptic potentials were unchanged in OLM cells of epileptic mice. These results are not consistent with the hypothesis of hyper-inhibition from VIP/CR bipolar cells impeding recruitment of OLM cells in advance of a seizure.SignificanceInadequate recruitment of inhibitory cells in general, and OLM cells in particular, may be a mechanism of seizure initiation, making it important to determine why OLM cells do not fire faster and provide preictal feedback inhibition when presynaptic CA1 pyramidal activity is ramping up. This study excludes aberrantly increased inhibition of OLM cells by VIP bipolar cells as the cause, pointing to other possibilities for investigation. ER -