Decreased cellular excitability of pyramidal tract neurons in primary motor cortex leads to paradoxically increased network activity in simulated parkinsonian motor cortex

Recent evidence suggests that the primary motor cortex (M1) layer 5B pyramidal tract (PT5B) neurons show a decreased intrinsic excitability in mouse models of parkinsonism, which perhaps plays an important role in the pathophysiology of parkinsonian motor symptoms. PT5B neurons project to outputs in the brainstem and the spinal cord, leading to the direct motor expression of Parkinson’s disease (PD) pathology. We set out to explore how the decreased PT5B neuron excitability influences the activity patterns of the M1 network. Using NEURON/NetPyNE simulators, we implemented detailed computer simulations of PT5B neurons based on control and 6-OHDA-treated mouse slice data. We placed these PT5B cells in an in vivo M1 network simulation, driven by ascending input from the thalamus and from other cortical areas. Simulated 6-OHDA-treated mouse PT5B neurons in an otherwise unmodified simulated M1 network resulted in major changes in LFP oscillatory power in the parkinsonian condition: an order of magnitude increase in beta band power around 15 Hz in the rest state and a lesser increase in beta power in the parkinsonian activated (movement) state. We demonstrated that relatively small changes in PT5B neuron excitability altered the patterns of activity throughout the M1 circuit. In particular, the decreased PT5B neuron excitability resulted in increased beta band power, which is a signature of PD pathophysiology.