Abstracts

Rationale: Somatostatin (SST)-expressing interneurons are known to be particularly susceptible to death in several pathological conditions, including the pilocarpine model of chronic limbic epilepsy. Sprouting of excitatory axons from granule cells also occurs in this model, raising the possibility that increased excitatory innervation of surviving SST interneurons might occur as a compensatory mechanism to maintain inhibitory strength in the network. Methods: We tested this hypothesis by obtaining whole cell and cell attached recordings from hilar SST interneurons in hippocampal slices from control and pilocarpine epileptic mice. To facilitate such recordings, genetically altered mice with GFP labeled SST cells were used. Recorded cells were labeled with biocytin for further anatomical analysis.Results: The frequency of both spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs) was significantly increased in epileptic vs control mice (sEPSC frequency 7.00 ± 0.27 Hz vs 2.33 ± 0.08 Hz and mEPSC frequency 3.62 ± 0.16 Hz vs 1.24 ± 0.05 Hz). The contribution of mEPSCs to total sEPSCs was significantly greater in cells from epileptic animals (70.8 ± 0.10%) than in controls (40.6 ± 0.04%). We observed no difference in paired pulse facilitation of EPSCs between control and epileptic groups in response to paired pulse stimulation (20 ms interpulse interval; 1.81 ± 0.22 in ctrl. vs. 1.77 ± 0.28 in epil.; p>0.5). Cell attached recordings indicated increased action potential firing (5.03 ± 0.88 Hz in epileptic vs 0.91 ± 0.18 Hz in control). Somatic areas increased from 258.2 ± 14.0 μm2 in control to 340.8 ± 5.5 μm2 in epileptic groups. An increase in cell capacitance (65.8 ± 4.7 pF in epileptic vs 40.7 ± 1.9 pF in control) and decrease in input resistance (158.9±10.2 ΜΩ epileptic vs 231.7 ± 16.5 ΜΩ control) were consistant with increased cell size. The kinetics (rise and decay times) of both sEPSCs and mEPSCs were significantly shifted toward slower rates in cells from epileptic animals (p<0.01, Mann-Whitney U test).Conclusions: The increase in s/mEPSC frequency and the absence of a significant difference in paired pulse facilitation of EPSCs suggests there is an increased number of synaptic contacts or release sites rather than an increase in probability of release. These results suggest that increased excitatory drive onto surviving hippocampal SST interneurons may act as compensatory mechanisms to offset loss of a portion of the inhibitory interneuronal population in epileptic animals.