Electrophysiological Characteristics of Globus Pallidus Neurons

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

Globus Pallidus external segment neuron classification in freely moving rats: a comparison to primates.

Globus Pallidus external segment (GPe) neurons are well-characterized in behaving primates. Based on their firing properties, these neurons are commonly divided into two distinct groups: high frequency pausers (HFP) and low frequency bursters (LFB). However, no such characterization has been made for behaving rats. The current study characterizes and categorizes extracellularly recorded GPe neurons in freely moving rats, and compares these results to those obtained by extracellular recordings in behaving primates using the same analysis methods. Analysis of our data recorded in rats revealed two distinct neuronal populations exhibiting firing-pattern characteristics that are similar to those obtained in primates. These characteristic firing patterns are conserved between species although the firing rate is significantly lower in rats than in primates. Significant differences in waveform duration and shape were insufficient to create a reliable waveform-based classification in either species. The firing pattern analogy may emphasize conserved processing properties over firing rate per-se. Given the similarity in GPe neuronal activity between human and non-human primates in different pathologies, our results encourage information transfer using complementary studies across species in the GPe to acquire a better understanding of the function of this nucleus in health and disease

Waveform characteristics.

<p>A and B: normalized average waveforms of HFP (blue) and LFB (red) neurons in primates (A) and rats (B). Inset: X represents the valley to peak duration, Y the valley width and Z the zero-cross parameter. C and D Bar plots representing waveform parameters in HFP (blue) and LFB (red) neurons in primates (C) and in rats (D).</p

Typical firing patterns observed in rats (A–C) and primates (D–F).

<p>Left panel: autocorrelation using a time window of ±1 s, middle panel: autocorrelation with x-axis expanded to ±0.1 s, right panel: spike train of the example neuron. A: example of HFP neuron exhibiting tonic Poisson firing without pauses. B: HFP neuron displaying pauses (pauser). C: LFB neuron (burster). D–F: same type of neurons as in A–C but in primates.</p

Verification of electrode placement in the Globus Pallidus of rats.

<p>A: a 60 micron slice showing electrode placement in a rat GPe following electrolytic lesion. B: Appropriate coronal section from atlas (Bregma: −2.28 mm; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045421#pone.0045421-Paxinos1" target="_blank">[47]</a>). C: Recording sites marked (grey rectangle) for all animals on a planar rat atlas slice (Bregma: −6.82 mm; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045421#pone.0045421-Paxinos1" target="_blank">[47]</a>).</p

Neuronal classification and firing properties in primates and rats.

<p>A and B: 3 dimensional presentation of firing properties leading to the formation of distinct clusters in primates (A) and rats (B). C–H: Bar plots representing parameters of the two groups (HFP - blue, LFB - red) in the two species (left two bars - primates, right two bars - rats).</p