Figure 5. Reversible axonal failure during STN-HFS.

FVs were recorded in bath solution containing reduced calcium (0.2 mm), picrotoxin (100 μm) and kynurenic acid (2 mm) to abrogate synaptic potentials. A, selected FV responses (every 1 s) elicited by STN trains of 10, 50 or 130 Hz were superimposed to show gradual shift in latency and peak amplitude. Most leftward black trace and red trace indicate first and last FV response, respectively, in each sequence. Sample traces were collected in a single recording session with inter-train intervals of 30 min each. Plots of normalized FV amplitudes (B) and averaged FV latencies (C) recorded in SNc during 10 s stimulus trains delivered to STN at different frequencies (10 Hz, n = 5; 50 Hz, n = 5; 130 Hz, n = 8). Averaged FV amplitudes at the end of train were 103 ± 6%, 26 ± 5% and 8 ± 4% of control for 10 Hz, 50 Hz and 130 Hz, respectively. STN trains for 10 s at 10 Hz and 50 Hz increased FV latency from 3.0 ± 0.1 ms to 3.5 ± 0.1 ms (P = 0.01) and to 4.0 ± 0.2 ms (P = 0.02), respectively. In view of the progressive decline of FVs during HFS (130 Hz), latencies were only determined over 4 s (from 3.0 ± 0.1 ms to 3.5 ± 0.1 ms at 4th s, P = 0.002). D, amplitude of FVs recovered quickly to pre-train level after cessation of trains. E, raising [K⁺]_o from 3 mm to 8 mm expedited FV rundown during STN-HFS in a reversible fashion (n = 5). Inset depicts superimposed FV responses to single STN stimulus in control and high [K⁺]_o solution. Elevation of [K⁺]_o increased latency to negative peak from 2.9 ± 0.2 ms to 3.4 ± 0.3 ms (P = 0.03) and reduced peak amplitude from 0.34 ± 0.03 mV to 0.23 ± 0.03 mV (P = 0.01; n = 5). F, lowering bath temperature to room temperature (RT) accelerated rundown of FV amplitude during HFS independent of extracellular calcium concentration (0.2 mm, n = 4; 2 mm, n = 6). For comparison, we replotted here the decay of FV amplitude at control (high) temperature already shown in B (green symbols each).