Propagation of Oscillations in the Indirect Pathway of the Basal Ganglia

Abstract

Oscillatory signals propagate in the basal ganglia from prototypic neurons in the external globus pallidus (GPe) to their target neurons in the substantia nigra pars reticulata (SNr), internal pallidal segment and subthalamic nucleus. Neurons in the GPe fire spontaneously, so oscillatory input signals can be encoded as changes in timing of action potentials within an ongoing spike train. When GPe neurons were driven by an oscillatory current in male and female mice, these spike-timing changes produced spike-oscillation coherence over a range of frequencies extending at least to 100 Hz. Using the known kinetics of the GPe->SNr synapse, we calculated the postsynaptic currents that would be generated in SNr neurons from the recorded GPe spike trains. The ongoing synaptic barrage from spontaneous firing, frequency-dependent short-term depression, and stochastic fluctuations at the synapse embed the input oscillation into a noisy sequence of synaptic currents in the SNr. The oscillatory component of the resulting synaptic current must compete with the noisy spontaneous synaptic barrage for control of postsynaptic SNr neurons, which have their own frequency-dependent sensitivities. Despite this, SNr neurons subjected to synaptic conductance changes generated from recorded GPe neuron firing patterns also became coherent with oscillations over a broad range of frequencies. The presynaptic, synaptic and postsynaptic frequency sensitivities were all dependent on the firing rates of presynaptic and postsynaptic neurons. Firing rate changes, often assumed to be the propagating signal in these circuits, do not encode most oscillation frequencies, but instead determine which signal frequencies propagate effectively and which are suppressed.Significance Statement:Oscillations are present in all the basal ganglia nuclei, include a range of frequencies, and change over the course of learning and behavior. Exaggerated oscillations are a hallmark of basal ganglia pathologies, and each has a specific frequency range. Because of its position as a hub in the basal ganglia circuitry, the globus pallidus is a candidate origin for oscillations propagating between nuclei. We imposed low amplitude oscillations on individual globus pallidus neurons at specific frequencies and measured the coherence between the oscillation and firing as a function of frequency. We then used these responses to measure the effectiveness of oscillatory propagation to other basal ganglia nuclei. Propagation was effective for oscillation frequencies as high as 100 Hz.

Phase Delays between Mouse Globus Pallidus Neurons Entrained by Common Oscillatory Drive Arise from Their Intrinsic Properties, Not Their Coupling

“…In 3 of the 16 neurons, the cell did not survive all 100 trials, but all neurons were recorded up to 50 Hz. As we reported previously ( Wilson and Jones, 2023 ), the sinusoidal drive influences the timing of the spikes ( Fig. 1 A ) causing the spike times to distribute nonuniformly across the phases of the sinusoidal waveform in a frequency-dependent manner.…”

“…The animal subjects used in this research have been detailed previously in Wilson and Jones (2023) . The study involved 14 mice of either sex aged between 74 and 193 d. Out of these, 10 were parvalbumin-Cre (PV-Cre), 2 were Npas1-Cre-tdTomato mice, and 2 were wild-type C57BL/6 mice without any genetic modifications.…”

“…In particular, how can GPe neurons receiving common sinusoidal input fire with nonzero phase delays relative to each other; and do these phase delays arise from intrinsic properties of GPe neurons or from their mutual connectivity? GPe neurons are autonomous pacemakers whose firing becomes entrained by oscillatory inputs over a wide frequency range of 10–70 Hz ( Chan et al, 2004 ; Deister et al, 2013 ; Wilson and Jones, 2023 ). We therefore addressed the following questions.…”