Project 1: Regulation of T-type calcium channel expression in chick nodose neurons. Ca²⁺ influx through voltage-gated Ca²⁺ channels regulates various developmental and physiological processes. Although the physiological role of voltage-gated Ca²⁺ channels is well established in many systems, we have very little understanding about the regulation of Ca²⁺ channel expression during neuronal differentiation. We have shown that the functional expression of T-type calcium channels in chick nodose neurons is developmentally regulated. The majority of immature nodose neurons express no T-type calcium currents, whereas mature neurons express large T-type calcium currents. Functional expression of T-type calcium channels is evoked by treatment of nodose neurons with a cardiac tissue extract or ciliary neurotrophic factor (CNTF). We are currently investigating the mechanism of regulation of T-type calcium channel expression by cardiac-derived factors and CNTF.

Project 2: Regulation of spinal motoneuron development by calcium-permeable AMPA receptors. Ca²⁺ influx through ionotropic glutamate receptors constitutes one main source of Ca²⁺ entry required for activity-dependent regulation of early embryonic development. In the CNS, NMDA receptors were originally thought to be the sole source of Ca²⁺ influx through glutamate receptors; however, AMPA receptors also allow a significant influx of Ca²⁺ ions. The Ca²⁺ permeability of AMPA receptors is regulated by the insertion of one or more edited GluR2 subunits, which significantly reduces the permeability of Ca²⁺ through the channel. Ca²⁺ permeable AMPA receptors are typically found at early stages of neuronal development. Our data indicate that chick lumbar motoneurons express Ca²⁺ permeable AMPA at embryonic day 6. However, AMPA receptors become Ca²⁺ impermeable by embryonic day 11 when most of neuromuscular development has been completed as revealed by the presence of contractile muscles and functional synapses capable of generating spontaneous contractions. We are currently investigating the mechanism that regulates the developmental switch in the Ca²⁺ permeability of AMPA receptors. We are especially interested in uncovering the functional role of Ca²⁺ permeable AMPA receptors in promoting early neuronal differentiation in the chick spinal cord.