Neuromodulation of current co-regulation

Ionic currents appear to be expressed in coordination with each other (Khorkova & Golowasch, 2007). This is partly regulated by the membrane potential across the membrane of these cells (Santin & Schulz, 2019, Golowasch, 2019a) and by the neuromodulatory environment in which they live. What the role of these neuromodulators is in particular is still poorly understood. By what mechanisms do they determine the intrinsic properties of the individual neurons so that their ionic currents remain coordinated? We study this using crab STG cultured cells and neurons in situ.

A branch of this line of research is to use pharmacological (Gray & Golowasch, 2016, Gray, Daudelin & Golowasch, 2017) and molecular biological tools (see figure below) to investigate the signaling pathways and molecular mechanisms activated by these neuromodulators.

References

1. Khorkova, O. and Golowasch, J. (2007) Neuromodulators, not activity, control coordinated expression of ionic currents. J. Neuroscience, 27: 8709-8718.

2. Golowasch, J. (2019a) Neuronal homeostasis: Voltage brings it all together. Current Biology (Dispatch), 29, R623–R646.

3. Santin, J.M., and Schulz, D.J. (2019). Membrane voltage is a direct feedback signal that influences correlated ion channel expression in neurons. Curr. Biol. 29, 1683–1688.e2.

4. Golowasch, J. (2019b) Neuromodulation of central pattern generators and its role in the functional recovery of CPG activity. J. Neurophysiol. 122: 300- 315. https://www.physiology.org/doi/pdf/10.1152/jn.00784.

5. Golowasch, J., Bose, A., Guan, Y., Salloum, D., Roeser, A and Nadim, F. (2017). A balance of outward and linear inward ionic currents is required for the generation of slow wave oscillations. J Neurophysiol 118: 1092–1104.

6. Bose, A., Golowasch, J., Guan, Y. and Nadim, F. (2014) Role of linear and voltage-dependent ionic currents in the generation of slow wave oscillations. J. Comp. Neurosci., DOI 10.1007/s10827-014-0498-4.

7. Gray, M., Daudelin, D.H. and Golowasch, J. (2017) Activation mechanism of a neuromodulator-gated pacemaker ionic current. J. Neurophys. 118: 595–609.

8. Gray, M. and Golowasch, J. Voltage Dependence of a Neuromodulator-Activated Ionic Current. eNeuro, 3(2): 1-19, 2016.