In M1 of two MPTP-treated macaques, the rest-rate decrease of pyramidal tract neurons did not change with axon conduction time; corticostriatal neurons did not decrease

Question: Parkinsonism decreases the activity of pyramidal tract neurons (PTNs) in primary motor cortex (M1), but not of corticostriatal neurons (CSNs). PTN axons have a wide range of diameters. Does the parkinsonian change depend on axon size? Approach: We used the open data of the original studies (DANDI:001636; Turner lab; 2 macaques; 566 single units before and after unilateral MPTP). The antidromic latency from the cerebral peduncle gives the conduction time of each PTN axon (0.65-5.5 ms, about 6-48 m/s). We froze an analysis plan before we computed any effect. We fit per-unit models of log rest rate (1 s center hold before the go cue) with state, log latency, their interaction and a monkey term. Results: The PTN rest rate decreased after MPTP (18.2 to 13.3 spikes/s; ratio 0.60, 95% CI 0.47-0.77) and the CSN rate did not (ratio 1.21, CI 0.90-1.63), which replicates Pasquereau and Turner (2011). The decrease did not change with latency (interaction +0.19, CI -0.40 to +0.78, p = 0.52; permutation p = 0.49; same in 7 robustness variants). Fast-half PTNs had ratio 0.53 (CI 0.36-0.79) and slow-half PTNs ratio 0.58 (CI 0.39-0.86). The latency distribution of identified PTNs did not change, so fast-axon PTNs did not drop out of the sample. On a log scale, the PTN change was clearly larger than the CSN change (ratio 0.50, CI 0.34-0.73), so low CSN rates do not explain the class difference. PTN movement activity decreased in both latency halves, with no latency interaction. Before MPTP, fast PTNs had a larger relative movement modulation (p = 0.005), but slow PTNs did not fire more at rest, which only partly agrees with Evarts (1965). Exploratory: the loss of PTN onsets in the 150 ms before movement (59% to 31%) came mostly from a 71 ms longer reaction time; onset relative to the go cue did not change significantly. Conclusion: in this model, the PTN decrease is a property of the projection class and is about proportional across PTN axon sizes. Limitations: 2 monkeys (monkey L gave only 10 post-MPTP PTNs); pre and post are different neurons; latency is a proxy for axon diameter; the confidence interval does not exclude a difference of up to about two-fold between fast and slow halves.

MPTP · parkinsonism · primary motor cortex · pyramidal tract neurons · corticostriatal neurons · antidromic latency · axon conduction velocity · selective vulnerability · macaque · DANDI 001636 · structure-function · replication