Electrophysiological characteristics of globus pallidus neurons

Abstract

Extracellular recordings in primates have identified two types of neurons in the external segment of the globus pallidus (GPE): high frequency pausers (HFP) and low frequency bursters (LFB). The aim of the current study was to test whether the properties of HFP and LFB neurons recorded extracellularly in the primate GPe are linked to cellular mechanisms underlying the generation of action potential (AP) firing. Thus, we recorded from primate and rat globus pallidus neurons. Extracellular recordings in primates revealed that in addition to differences in firing patterns the APs of neurons in these two groups have different widths (APex). To quantitatively investigate this difference and to explore the heterogeneity of pallidal neurons we carried out cell-attached and whole-cell recordings from acute slices of the rat globus pallidus (GP, the rodent homolog of the primate GPe), examining both spontaneous and evoked activity. Several parameters related to the extracellular activity were extracted in order to subdivide the population of recorded GP neurons into groups. Statistical analysis showed that the GP neurons in the rodents may be differentiated along six cellular parameters into three subgroups. Combining two of these groups allowed a better separation of the population along nine parameters. Four of these parameters (Fmax, APamp, APhw, and AHPs amplitude) form a subset, suggesting that one group of neurons may generate APs at significantly higher frequencies than the other group. This may suggest that the differences between the HFP and LFB neurons in the primate are related to fundamental underlying differences in their cellular properties.

Figure 1. Extracellular properties of different cellular populations of the primate GPe.

A. Traces from representative neurons from the two major neuron types in the GPe: high frequency pauser (HFP–left) and low frequency burster (LFB–right), shown at long and short time scales (top, 1 s trace; bottom, 100 ms trace). B. Autocorrelation functions of the neurons in A (maximal offset ±1 s). C. Mean firing rate of the two groups. D. Mean ISI distribution coefficient of dispersion of the two groups. E. Mean spike shape of the neurons shown above (HFP–black, LFB–gray). F. Mean spike duration of the two groups, Error bars indicate SEM, ** p≪0.01 Mann-Whitney U-test.

Figure 2. Intracellular and extracellular recordings from rat GP neurons.

A, A continuous recording of the membrane potential recorded in the whole-cell mode of the patch-clamp technique (top trace) simultaneously with the extracellular potential (bottom trace). B, Spike-triggered average of the membrane potential during an AP (top trace) and the extracellular potential (bottom trace). The first derivative of the AP was superimposed on the extracellular potential (gray line). C, Event-triggered average of the voltage-clamp membrane current recording from a cell-attached patch (gray line) superimposed on the average of the extracellular potential (black line). All traces were filtered at 5 kHz and sampled at 20 kHz.

Figure 3. Spontaneous firing of GP neurons in acute rat brain slices.

A, Population average of the spontaneous firing frequency recorded from GP neurons in the cell-attached mode (n = 76). B, Population average of the spontaneous firing frequency recorded from GP neurons in the whole-cell mode (n = 76). C, Distribution of the average firing frequency recorded in the cell-attached mode across the population. The frequency value used to construct the histogram was taken 200 s after the start of the recording to ensure stability. D, Distribution of the average firing frequency recorded in the whole-cell mode across the population. The frequency value used to construct the histogram was taken 200 s after the start of the recording to ensure stability. E, Correlation between the values used to generate C and D.

Figure 4. The width of the intracellular AP can be extracted from extracellular recordings.

A, The intracellular AP recorded in the whole-cell mode (top trace) and the transmembrane current recorded in the cell-attached mode (bottom trace, black line). The first derivative of the intracellular trace is superimposed on the extracellular trace (bottom trace, gray line). The half-width of the intracellular AP is indicated by the horizontal line. The vertical lines locate the half-width of the intracellular AP on the extracellular trace. B, Correlation between the half-width of the extracellular and intracellular recordings of the AP for all neurons recorded (n = 76). C, Distribution of the intracellular AP half-width for all neurons recorded. D, Distribution of the extracellular AP half-width for all neurons recorded.

Figure 5. Representative recordings from GP neurons of three visually separated subgroups.

Ai, Bi, and Ci, responses of GP cells to depolarizing current steps (50 pA increment, 600 ms) applied from 0 to 550 pA using whole-cell configuration of the patch-clamp technique. Representative membrane potentials recorded in response to 100 pA are given for each cell type. Sampled at 20 kHz and filtered at 10 kHz. Aii, Bii, and Cii, responses of GP cells to hyperpolarizing current steps applied from 0 to −450 pA (50 pA increment, 600 ms) using the whole-cell configuration of the patch-clamp technique.

Figure 6. Average parameters of GP neurons.

Ai, Voltage-current curves for type A neurons (n = 14). Bi, Voltage-current curves for type B neurons (n = 24). Ci, Voltage-current curves for type C neurons (n = 38). In Ai, Bi and Ci, • - data measured to calculate input resistance; ○ - data measured to estimate the influence of I_h on membrane potential. Aii, lines plotted by exponential fitting to curves from action potential frequency vs. injected currents. F_max and current required to reach 63% of maximal firing rate were extracted by exponential fit for type A neurons. Values and error bars are mean ± S.E. Bii, As in Aii but for type B neurons. Cii, As in Aii but for type C neurons.

Figure 7. Representative intracellular and extracellular APs.

A, Spontaneous AP recorded in the whole-cell mode superimposed at an extended time scale for each cell type ( ─ type A; ─ type B; ─ type C). B, Spontaneous AP recorded in cell-attached mode superimposed at an extended time scale for each cell type (─ type A; ─ type B; ─ type C).

Figure 8. Histograms of several extracellular and intracellular properties of GP cells.

A, Half-width of the extracellular AP (AP_ex) calculated as in figure 4. B, Half-width of the intracellular AP (AP_in) calculated as in figure 4. C, The intracellular AP adaptation ratio calculated as the ratio between the amplitude of the last AP and that of the first AP in a train of APs generated by current injection. D, The slow phase of the AHP (AHP_s). AHP amplitude was measured from threshold. E, Sag of membrane potential induced by activation of I_h. Sag was calculated as the difference between the maximal deflection of the membrane potential following a hyperpolarizing step and the deflection at the end of the pulse. F, Maximal frequency calculated for each cell from F-I curves, similar to those in figure 6.