Charles J. Wilson Neuroscientist.21(5):530-539.

What is the meaning of an action potential?  There must be different answers for neurons that fire spontaneously, even in the absence of synaptic input, and those driven to fire from a resting membrane potential. In spontaneously firing neurons, the occurrence of the next action potential is guaranteed; only variations in its timing can carry the message. In the basal ganglia the globus pallidus, the substantia nigra, and the subthalamic nucleus consist of neurons firing spontaneously. They each receive thousands of synaptic inputs, but these are not required to maintain their background firing. Instead, synaptic interactions among basal ganglia nuclei comprise a system of coupled oscillators that produces a complex resting pattern of activity. Normally, this pattern is highly irregular and uncorrelated, so that the firing of each cell is statistically independent of the others. This maximizes the potential information that may be transmitted by the basal ganglia to its target structures. In Parkinson’s disease, the resting pattern of activity is dominated by a slow oscillation shared by nearly all of the neurons. Treatment with deep brain stimulation may gain its therapeutic value by disrupting this shared pathological oscillation, and restoring independent action by each neuron in the network.

Figure 1 - The Disinhibition Hypothesis, schematically showing some the relevant synaptic circuits and their characteristic responses to cortical stimulation (at arrow).

Figure 2 - mechanism of oscillation of basal ganglia neurons. A. The membrane potential trajectory of a subthalamic neuron firing rhythmically in a slice in the absence of synaptic inputs. B. Ionic currents responsible for the intrinsic resting oscillation of the cell membrane.

Figure 3 - synaptic influence on spike timing. A. Membrane potential of a subthalamic nucleus neuron perturbed by an evoked synaptic excitation at time tstim following an action potential. As a result, of the synaptic input the progression of the cell toward firing is advanced, and the cell fires earlier by amount ΔISI. Both tstim and ΔISI can be converted to phase units by dividing by the average interspike interval (ISI). The inset illustrates the cells progression to firing on the circle, in phase units, where firing occurs at phase 0. The stimulus causes a shift in cell phase which is retained and appears as an early action potential. B. The phase shifts caused by many synaptic inputs delivered at various phases. The phase shift for the stimulus (scaled by stimulus size) is used to generate a phase resetting curve, illustrating the phase-dependency of the synaptic effect (Wilson and others 2014).

Figure 4. Antiphase firing of pair of globus pallidus cells connected by artificial inhibitory synapses. The traces show a paired recording from globus pallidus cells connected reciprocally using the dynamic clamp technique. Each time one cell fires, the dynamic clamp circuit creates an artificial inhibitory synaptic conductance and IPSP in the other. Also note note spontaneous IPSPs in one of the cells (at arrowheads), probably arising from a natural synaptic inhibition from another (unseen) globus pallidus neuron firing at about the same rate.