Thalamocortical (TC) relay neurons generate antidromic and orthodromic action potentials (APs) during thalamic deep brain stimulation (DBS). To maintain signaling, each AP requires Na+/K+ pump to expend adenosine triphosphate (ATP) to restore Na+ and K+ gradients. Our aim was to estimate the energy demand associated with AP generation and propagation within TC relay cells during DBS. We used a morphology-based computational model to simulate the APs at different locations. We determined AP energy cost by calculating the amount of ATP required to reverse Na+ influx during the spike and measured metabolic efficiency by using Na+/K+ charge overlap. The ATP cost for AP generation exhibited location dependence, which was determined by spike shape, spatial morphology, and heterogeneously distributed currents. The APs in the axonal initial segment (AIS) were energetically efficient, but backpropagation to the soma and forward propagation to the axon were inefficient. Due to large surface area, the soma and AIS dominated the overall ATP usage. The AP cost also depended on membrane potential, which controlled T-Type Ca2+ conductance and degree of availability of Na+ and K+ channels. The excitatory/inhibitory synaptic inputs affected spike cost by increasing/reducing the excitability of local cells. There was a tradeoff between AP cost and firing rate at high firing frequencies. We explained a fundamental link between biophysics of ionic currents, spatial morphology of neural segments, and ATP cost per AP. The predictions should be considered when understanding the functional magnetic resonance imaging data of thalamic DBS.
All Science Journal Classification (ASJC) codes
- Biomedical Engineering