Date of Award
Doctor of Philosophy in Biology - (Ph.D.)
Federated Department of Biological Sciences
Jorge P. Golowasch
Eric Scott Fortune
Dawn Marie Blitz
Neuronal output is shaped by extrinsic modulation as well as modulation of intrinsic properties of individual neurons, mediated by activity-dependent changes in the expression levels of voltage-gated ionic currents. Activity-dependent regulation of ionic currents is a mechanism by which electrical output of a neuron feeds back onto the expression of its own ion channels to alter cellular excitability in response to stimuli. Neurons alter their intrinsic properties to achieve long lasting changes involved in development, learning and memory formation and vital functions of organ systems such as locomotion and digestion. At the same time, plasticity of neuronal excitability driven by previous experience requires mechanisms to promote stability to maintain physiological function, and many examples of this type of homeostatic plasticity changes have been reported. At the same time, neuromodulation can alter electrical output indirectly via ligand-gated receptors and second messenger pathways and potentially affect activity-dependent effects. Activity-dependent regulation of ionic currents functions to allow neurons to track their own electrical activity and adjust their intrinsic properties in response to changing synaptic drive or other inputs to maintain their functional output. This phenomenon has been demonstrated to occur over the course of minutes and is a relatively fast process. Neuromodulators exert long-term effects on ionic currents via activation of cellular signaling pathways that do not directly affect ionic current levels. Neuromodulation and activity-dependent effects can alter neuronal networks on different time scales, e.g. over several hours to days to accommodate the needs of the behaving organism such as in transitions between sleep and waking states. However, this is not necessarily so, and the possibility of real-time interactions exist and needs to be examined.
This dissertation demonstrates that activity-dependent regulation of K+ currents is gated by the neuromodulatory environment and can be altered depending on the activation of a ligand-gated peptide receptor. This study demonstrates novel findings of interactions between metabotropic receptor activation and modulation of highly K+ currents after acute changes to activity and neuromodulatory input.
Salloum, Dalia, "Regulation of voltage-gated K+ currents in motor neurons: activity-dependence and neuromodulation" (2017). Dissertations. 5.