Voltage-gated L-type calcium channels and circuit plasticity

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Calcium ions are important for a variety of neuronal functions that are enabled by calcium entry into cells through calcium channels, a family of proteins embedded in the cell membrane. Among the family of calcium channels is a subclass called L-type calcium channels. These are particularly important for regulating the electrical excitability of nerve cells and for the release of neurotransmitters required to form long-term changes in circuit function reflecting memory formation. Given the pivotal roles for L-type calcium channels, it is critical to understand how these channels are modulated at the molecular level to regulate their biophysical properties and the density of channel protein positioned at the plasma membrane. This equipment application will directly benefit the NSERC funded Discovery grant programs of Drs. R.W. Turner and G.W. Zamponi who work on different aspects of L-type calcium channels in a cortical structure called the hippocampus. Dr. Turner’s program is focused on internal accessory proteins that regulate the magnitude of calcium current through L-type channels (biophysical properties), and Dr. Zamponi the molecular steps that regulate trafficking of channels to and from the membrane (channel density). Both labs currently focus their work on recordings from isolated neurons or circuits in vitro in conjunction with laser or LED-based excitation of light-activated molecules expressed in select neurons (optogenetics). This proposal will introduce the capability of obtaining patch clamp recordings in the intact hippocampus of mice in vivo through stereotaxic positioning of electrodes for recording and optogenetic stimulation. It will further allow the use of a wireless system to simultaneously record unit activity and optogenetically stimulate hippocampal neurons or the incoming pathways. In this way the in vitro work conducted to date will be advanced to interpreting the function of L-type calcium channels in live and freely moving animals performing behavioural tests known to depend on hippocampal function. These studies will thus elevate our research programs to the next level by enabling patch clamp recordings and behavioural testing in the live animal, substantially increasing our collaborative capabilities, competitive stance for publication in top journals, and greatly expand the experimental opportunities for our trainees.