Fig. 3: Temporal evolution may reflect synaptic dynamics of ERNA.
From: Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson’s disease
A Example trace of microelectrode recording in the STN illustrating that the depression of inhibitory inputs during the first 10 pulses for the first peak (P1; dark blue arrows) is associated with an increase in amplitude of a second, resonant evoked field (P2; light blue arrows). B Group data (n = 12.) of differential dynamics of P1 (dark blue) and P2 (light blue) across successive stimuli; y-axis depicts P1 and P2 peak amplitudes relative to the first respective peak in the stimulus train. Shade represents standard error of the mean. C Scatter plot illustrating the relationship between the dynamics of the decaying P1 (x-axis) and increasing P2 (y-axis); dynamics were measured as P140-45th / P1first and P240-45th / P2first. Rho and p value are taken from Spearman’s correlation (Rho = −0.6853; p = 0.0173). D Conceptual schematic to illustrate how STN stimulation may trigger a cascade of synaptic events that gives rise to ERNA. Left: Schematic representation of activated fibers at two timepoints (1a/b and 2) during a single interstimulus interval. Note that (1a) and (1b) are expected to occur simultaneously within a “monosynaptic” time course in direct response to individual stimuli, whereas (2) occurs subsequently/consequently, at a “disynaptic” time course (depicted by blue shading). Right: These synaptic responses change in amplitude across successive interstimulus intervals as a result of short-term synaptic plasticity. Vertical lines represent individual stimuli at HFS. Blue positive-going evoked field potentials correspond to inhibitory afferent activations, whereas negative-going red evoked field potentials represent activations of excitatory inputs. (1a) depicts direct simultaneous activations of the inputs to STN. Sustained GPe transmission is paired with rapidly depressing cortical transmission, which leads to a sustained net inhibition in STN (this inhibits STN spike firing and produces a hyperpolarization of the membrane potential which is reflected as P1 of STN ERNA, filled gray). (1b) depicts direct activation of STN efferent outputs (even though spike firing is inhibited by GPe activation, STN efferent axons are nevertheless expected to be activated by DBS pulses) and GPe-GPe collaterals (by way of antidromic activation of GPe-STN projections, and subsequent invasion of GPe-GPe collaterals). Sustained GPe transmission paired with even more sustained STN transmission leads to an increasing net excitation in GPe. (2) depicts that the increasing net excitation in GPe feeds back to the STN, producing recurrent inhibition of STN (this produces a second hyperpolarization of the membrane potential in STN within the interstimulus interval, which is reflected as P2 of STN ERNA, filled black). Effectively, the recurring activations of GPe inhibit the generation of STN spike firing, while contributing to the positive-going voltage peak deflections in the ERNA waveform (i.e., due to a loss of negatively-charged ions in the extracellular field potential recordings due to GABAergic activations).
