The cortex and hippocampus are two key brain areas that play critical roles in normal functions such as learning and memory as well as disorders such as epilepsy. Our research interests lie in understanding how neurons within these brain areas process information and thereby influences neural network activity. We are particularly interested in determining how voltage-gated ion channels regulate neuronal intrinsic excitability and synaptic transmission in cortical and hippocampal neurons. Specific projects include:

Presynaptic HCN channels and neuronal excitability

We have demonstrated that HCN channels are located at certain glutamatergic synaptic terminals in the adult entorhinal cortex inhibit synaptic release by restricting the activity of low threshold T-(Ca_V3.2) Ca²⁺ channels. Interestingly, the expression of pre- and post-synaptic HCN channels in the entorhinal cortex is differentially regulated. We are now using a combination of multi-photon imaging and electrophysiology to investigate which particular cortical neurons express pre-synaptic HCN channels and the cellular mechanisms that dictate which synapses may preferentially express these channels.

Function and Regulation of Axonal K_V7 channels

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 these K_V7 subunits are targeted to the axon initial segments of hippocampal and cortical pyramidal neurons. K_V7 mutations that cause BFNC impair axonal targeting of these channels. We have determined that the K_V7 channels located at the axon initial segments of hippocampal pyramidal and granule cells regulate the action potential threshold and, thereby, neuronal firing. Interestingly, neurotransmitters such as acetylcholine cause long-term plasticity of these axonal K_V7 channels. We are currently investigating the mechanisms by which neurotransmitters may regulate axonal K_V7 channel activity and the impact of this on neuronal and network excitability.  

In addition to being present on axon initial segments, K_V7 channels are also found on axon nodes of Ranvier and synaptic terminals. We are interested in understanding how these channels contribute to information processing within axons and synaptic release.

T-type Ca²⁺ channels and medial entorhinal cortical stellate neuron excitability.

Layer II stellate neurons within the medial entorhinal cortex play a significant role in spatial information processing. Their properties vary along the dorsal-ventral axis. A contributing factor is the higher density and/or altered biophysical characteristics of voltage-gated K+ and HCN channels. We have found, though, that T-type Ca2+ channel function differentially affect dorsal and ventral medial entorhinal  cortical stellate neuron function. We are currently exploring the underlying mechanisms for this.