Thalamic neuronal activity in dopamine-depleted primates: evidence for a loss of functional segregation within basal ganglia circuits - PubMed (original) (raw)

Thalamic neuronal activity in dopamine-depleted primates: evidence for a loss of functional segregation within basal ganglia circuits

Mathias Pessiglione et al. J Neurosci. 2005.

Abstract

Different analyses of neuronal activity in primate models of Parkinson's disease (PD) have resulted in two different views on the effects of dopamine depletion. The first is based on the higher firing rate and bursty firing pattern, and assumes that dopamine depletion results in a hyperactivity of basal ganglia (BG) output structures. The second is based on the less-specific responses to passive joint manipulation and the excessive correlations between neuronal discharges, and assumes that dopamine depletion results in a loss of functional segregation in cortico-BG circuits. The aim of the present study was to test out the predictions of these two different views on thalamic neuronal activity. Three male vervet monkeys (Cercopithecus aethiops) were progressively intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal activities were characterized using standard analyses (firing rates and patterns, receptive fields, and cross-correlations) and compared between the normal, asymptomatic (before the stabilization of motor symptoms), and parkinsonian (with persistent akinesia and rigidity) stages of MPTP intoxication. The pallidonigral thalamus (receiving projections from the BG) was characterized in both the asymptomatic and parkinsonian states by (1) an unchanged firing rate and pattern and (2) a proliferation of nonspecific neurons and correlated pairs. In contrast, the cerebellar thalamus (receiving projections from the cerebellum), was characterized by no change (asymptomatic state) or minor changes (symptomatic state). Thus the major dysfunction after dopamine depletion appeared to be the loss of functional segregation within cortico-BG circuits, which could also be at the heart of parkinsonian pathophysiology.

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Figures

Figure 1.

Figure 1.

Anatomical localization of recording sites in the three clinical states. A, Mapping of all sites recorded in the two hemispheres of the three monkeys, pooled on four frontal planes ranging from +3.3 to +6.3 mm from the PC. The border (dashed line) between the pallidonigral (open circles) and the cerebellar (filled circles) thalamus appears only on the last plane (right column). The pallidal thalamus is more lateral than the nigral thalamus, but the border between these two territories remains hard to delineate. B, Example of a calbindin-stained section with a highly visible trace of an electrode track (arrow) corresponding to the last recordings in the parkinsonian state. C, Enlarged view of the boxed section in B showing the border between the pallidal and cerebellar thalamus. Only the pallidal thalamus contains black-stained neurons. AN, Anterior nucleus; Cer, cerebellar thalamus; Cd, caudate nucleus; MD, mediodorsal nucleus; MT, mamillothalamic tract; Nig, nigral thalamus; Pal, pallidal thalamus; Ret, reticular nucleus.

Figure 2.

Figure 2.

Evolution of firing rates with MPTP intoxication. Values are means ± SD. Bars indicate the percentage of neurons with a firing rate within each of the following six ranges: 0-10, 10-20, 20-30, 30-40, 40-50, and >50 spikes/s. Data of the three monkeys were pooled.

Figure 3.

Figure 3.

Evolution of firing patterns with MPTP intoxication. A, Examples of the four firing patterns that were characterized. B, Distribution of the different firing patterns. A χ2 test was performed to compare the percentage of neurons with bursts (regardless of whether or not they were rhythmic) between two successive clinical states. No significant difference was found. N, Normal; aS, asymptomatic; P, parkinsonian. Data of the three monkeys were pooled.

Figure 4.

Figure 4.

Evolution of receptive fields with MPTP intoxication. A, Examples of receptive fields characterized along an electrode track in the normal and asymptomatic states. The two tracks were made in the pallidonigral thalamus of the same monkey and positioned at the same stereotactic coordinates within the recording chamber, as illustrated on the frontal section. Dorsoventral coordinates of neurons (circles) are in proportion to their position on the vertical axis. Neurons that did not respond to joint manipulation are shown as slashed circles. contra, Contralateral; ipsi, ipsilateral. B, Distribution of the different levels of specificity. A χ2 test was performed to compare the percentage of specific neurons (responding to one joint only) between two successive clinical states. **p < 0.01. N, Normal; aS, asymptomatic; P, parkinsonian. The data of the three monkeys were pooled.

Figure 5.

Figure 5.

Evolution of cross-correlations with MPTP intoxication. A, Examples of spike trains and cross-correlograms for noncorrelated and correlated pairs recorded in the normal and asymptomatic states. The two recordings were made in the pallidonigral thalamus of the same monkey. The two unit activities are displayed above and below the horizontal line. For the cross-correlograms, the _y_-axis is in arbitrary units and the _x_-axis is in milliseconds. B, Distribution of correlated and noncorrelated pairs. A χ2 test was performed to compare the percentage of correlated pairs between two successive clinical states. *p < 0.05; ***p < 0.001. N, Normal; aS, asymptomatic; P, parkinsonian. The data of the three monkeys were pooled.

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