Section 8.4 Neurophysiology and Cognitive Neuroscience: Adaptive modulation of excitability in motor neurons
Abstract
The long-term objective of this exploratory research project is to uncover cellular mechanisms involved in adaptation in the excitability of spinal motoneurons, in response to changes in overall motor activity. The central hypothesis of the work is that alteration of the function of KCNQ/Kv7.2 potassium channels and changes in the properties of the axonal initial segment (AJS) are the primary mechanisms by which spinal motoneurons adapt to prolonged network activation (the cellular equivalent of physical fatigue). Work to achieve the goals of this proposal includes a combination of immunohistochemistry and electrophysiological techniques to investigate the extent that changes in the somatodendritic and AIS responsiveness of motoneurons and the shape of the AIS can explain the complex effects of prolonged spinal network activation on motoneuron excitability. Specific KC Q/Kv7 potassium channel modulating drugs will be used to dissect the contribution of the channels to the excitability of spinal motoneurons in both baseline and adapted states, differentiating their somatodendritic and axonal contributions. Immunohistochemical labeling of the AIS in baseline and adapted neurons can identify activity-dependent changes in AlS geometry and distance from the soma. We will also develop more detailed computational models of spinal motoneuron activity before and after persistent network activation exploiting a multi-objective evolutionary algorithm (MOEA) approach capable of matching multiple selection criteria simultaneously and generating entire collections of neuronal models. The MOEA approach will generate a set of co-regulation rules capturing the relationships between model parameter values under the two experimental conditions (control and prolonged activated), thus providing further insights into the phenomena of plasticity in these motoneurons and at the AIS. Computational models can then be constrained with biophysically-plausible hypothesis testing.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1510559
Entities
People
- Melissa A Harrington
Organizations
- Army Contracting Command
- Delaware State University
- United States Army