Voltage-gated ion channels are important determinants of neuronal excitability. The hippocampus and cortex are two key brain areas involved in normal functions such as learning and memory as well as disorders such as epilepsy. Our research interests lie in understanding how voltage-gated ion channels activated at subthreshold membrane potentials affect hippocampal and cortical cell excitability under physiological as well as epileptogenic conditions. Specific projects include:

Dendritic HCN channels and temporal lobe epilepsy: 

The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are concentrated in the apical dendrites of hippocampal and cortical pyramidal neurons. We, and others, have demonstrated that dendritic HCN channel expression in these neurons is significantly altered following the onset of epilepsy. Further, we have shown that loss of the HCN1 subunit enhances entorhinal cortical excitabiity and increases the susceptibility to epilepsy. Our goal is to understand the molecular and cellular mechanisms by which a loss of HCN channels may lead to epileptogenesis.

Presynaptic HCN channels, Ca²⁺ channels and neuronal excitability

We have recently demonstrated that HCN channels are also located at certain glutamatergic synaptic terminals in the adult entorhinal cortex where, by restricting the activity of low threshold T-(Ca_V3.2) Ca²⁺ channels, they inhibit synaptic release. Using a combination of multi-photon imaging and electrophysiology, we are now investigating which neurons in particular express pre-synaptic HCN channels and whether similar molecular mechanisms regulate the trafficking and plasticity of pre- and post-synaptic HCN channels.

Axonal K_V7 channels and cell excitability

Mutation in two types of K_V7 subunits (K_V7.2 and K_V7.3) have been associated with Benign Familial Neonatal Convulsions (BFNC). Recent evidence shows that K_V7 channels are targeted to the axon initial segment of hippocampal and cortical pyramidal neurons. K_V7 mutations that cause BFNC impair axonal targeting of these channels. However, very little is known about the functional role of axonal K_V7 channels. Our aim is to understand how modulation of axonal K_V7 channels affects cell excitability and synaptic integration.