Dispersed Activity during Passive Movement in the Globus Pallidus of the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Treated Primate

Parkinson's disease is a neurodegenerative disorder manifesting in debilitating motor symptoms. This disorder is characterized by abnormal activity throughout the cortico-basal ganglia loop at both the single neuron and network levels. Previous neurophysiological studies have suggested that the encoding of movement in the parkinsonian state involves correlated activity and synchronized firing patterns. In this study, we used multi-electrode recordings to directly explore the activity of neurons from the globus pallidus of parkinsonian primates during passive limb movements and to determine the extent to which they interact and synchronize. The vast majority (80/103) of the recorded pallidal neurons responded to periodic flexion-extension movements of the elbow. The response pattern was sinusoidal-like and the timing of the peak response of the neurons was uniformly distributed around the movement cycle. The interaction between the neuronal activities was analyzed for 123 simultaneously recorded pairs of neurons. Movement-based signal correlation values were diverse and their mean was not significantly different from zero, demonstrating that the neurons were not activated synchronously in response to movement. Additionally, the difference in the peak responses phase of pairs of neurons was uniformly distributed, showing their independent firing relative to the movement cycle. Our results indicate that despite the widely distributed activity in the globus pallidus of the parkinsonian primate, movement encoding is dispersed and independent rather than correlated and synchronized, thus contradicting current views that posit synchronous activation during Parkinson's disease

Movement and neuronal response quantification.

<p><b><i>A</i></b>, Illustration of the passive movement of the monkey's upper limb, indicating the displacement (x), velocity (v) and acceleration (a) values. <b><i>B</i></b>, Example of a raw accelerometer signal. Vertical dashed lines indicate the beginning and end of movement. <b><i>C</i></b>, Enlargement of the signal from <b><i>B</i></b> (black), overlaid with the filtered signal (blue) and the identification of the movement cycles (red asterisks). <b><i>D</i></b>,<b><i>E</i></b>, Movement peri-event-time-raster (top) and movement peri-event-time-histogram (mPETH) (bottom) of a GPe cell are presented using (<b><i>D</i></b>) The original duration of the movement cycles (marked by asterisks) and (<b><i>E</i></b>) scaled to 1 s cycle duration.</p

Single neuron movement encoding in the GP.

<p><b><i>A</i></b>, Mean firing rates (±SEM) of GPe (blue) and GPi (red) neurons during different parts of the experimental protocol. * p<0.001. <b><i>B</i></b>, Example of a raw spike train recorded from a GPi neuron during movement (black). The simultaneously recorded filtered accelerometer signal is superimposed (red). <b><i>C</i></b>, Example of a raster (top) and mPETH (bottom, blue) of a GPe cell. The red curve indicates the sine fit for the mPETH, and its parameters are shown (R² = 0.96): horizontal solid line indicates r₀, horizontal dashed line indicates the phase and vertical line indicates the amplitude. <b><i>D</i></b>, Compass plot of the sine fit phase (direction of arrow) and amplitude (length of the arrow) of all analyzed cells. <b><i>E</i></b>, Scatter plot of the firing rate prior to movement relative to the r₀. The regression lines are shown in solid lines, dashed line indicates equality line. In <b><i>D</i></b>,<b><i>E</i></b>, GPe neurons in blue, GPi neurons in red.</p

Interaction between pairs of pallidal neurons during movement.

<p><b><i>A</i></b>, Compass plot of interaction between responses to movement of all recorded pairs of neurons. Each arrow represents a pair of neurons: direction indicates the offset phase (Δθ) and length represents the multiplication of amplitudes of the sine fits (A1 and A2) on a logarithmic scale. <b><i>B</i></b>, Histogram of signal correlation. <b><i>C</i></b>, Histogram of noise correlation. Gray dashed lines in <b><i>B</i></b> and <b><i>C</i></b> indicate the mean value.</p