Disinhibition – characterized by a reduction in network inhibition via interactions between inhibitory interneurons that increases the excitability of principal neurons – has been proposed as an important factor in numerous neurological diseases, including epilepsy. Electrical connections via gap junctions between interneurons can affect the synchronisation of neuronal firing. Thus, gap junctions are also likely to play a role in epilepsy.

HCN channels are widely expressed in the central nervous system, and mounting evidence indicates their functional involvement in human epilepsies (Hung et al., 2021, Bleakley et al., 2021, Shah, 2014). Of the four known isoforms, the HCN1 subtype appears to have the strongest association with epilepsy, with several de novo variants reported in patients with developmental and epileptic encephalopathy (Hung et al., 2021, Bleakley et al., 2021, Bonzanni et al., 2018).  

The piriform cortex, a three-layered primary olfactory cortex, has long been recognised as a highly epileptogenic site. However, the connections between inhibitory interneurons in the piriform cortex are still unclear. Hence, this project aimed to: 1) investigate the chemical and electrical synaptic connections between specific subtypes of inhibitory interneurons in the piriform cortex using dual whole-cell recordings, and 2) explore the functional properties of these interneurons in the piriform cortex, utilizing a transgenic mouse model with mutant HCN1 channels.