Abstracts

Rationale: Epilepsy is a disorder of network excitability and synchrony. In the dentate gyrus, excitability and network rhythms are regulated by GABAergic fast-spiking basket cells (FS-BCs), which express parvalbumin and underlie granule cell perisomatic inhibition. While synaptic transmission from FS-BCs to granule cells appears compromised after pilocarpine-induced status epilepticus (SE), whether GABAergic and electrical synapses to FS-BCs are modified after SE is unknown. Identifying how inhibitory and electrical synapses to FS-BC are altered after SE is important for evaluating dentate inhibitory circuit function during development of epilepsy. Methods: Whole-cell, patch-clamp recordings were conducted in hippocampal slices from male rats obtained 1 week after pilocarpine induced status epilepticus (SE) and in saline-injected controls. A combination of intrinsic physiology and morphological analysis following post-hoc immunohistochemistry was used for cell identification. Results: The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in morphologically and physiologically identified FS-BCs was reduced one week after SE (sIPSC frequency in Hz, control: median=6.9, IQR=3.7-13.5, n=10 cells; post-SE, median=5.0, IQR=2.6-10.4, n=9 cells, p<0.05 K-S test). However, FS-BC sIPSC amplitude was not altered after SE. Paired interneuronal recordings demonstrated that FS-BCs in control and post-SE rats received GABAergic synaptic inputs from both FS-BCs and non-fast-spiking interneurons in the hilar-granule cell layer border. While the probability of synaptic connections between FS-BCs were not different in slices from control and post-SE rats (connection probability, control: 8%, 4 of 50 pairs, post-SE: 8.6%, 5 of 60 pairs), preliminary data revealed a reduction in the release probability at inhibitory synapses between FS-BCs which did not reach statistical significance. Similarly, the probability of synaptic connections from non-fast-spiking interneurons to FS-BCs was not altered after SE (control: 6.0%, 5 of 85 pairs tested; post-SE: 6.8%, 5 of 74 pairs). However, consistent with a potential decrease in the probability of release, short-term depression of GABAergic synapses from non-fast-spiking interneurons to FS-BCs was reduced one week after SE (IPSC3/IPSC1 at 50 Hz, control: 0.64±0.16, n=4; post-SE: 0.98±0.08, n=3, p<0.05). Unlike inhibitory synaptic connections between FS-BCs, the probability of electrical contacts between FS-BCs was decreased after SE (probability of electrical coupling, control: 53.3%, 16 of 30 pairs, post-SE: 16%, 4 of 25 pairs, p<0.05 by chi-square test).The coupling coefficient of electrically coupled FS-BCs was not altered after SE (control: 0.05±0.02, n=11; post-SE: 0.05±0.02, n=4, p>