Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates

doi:10.1016/S0166-2236(97)01151-X

Trends in Neurosciences

Volume 21, Issue 1, 1 January 1998, Pages 32-38

https://doi.org/10.1016/S0166-2236(97)01151-X Get rights and content

Abstract

There are two views as to the character of basal-ganglia processing – processing by segregated parallel circuits or by information sharing. To distinguish between these views, we studied the simultaneous activity of neurons in the output stage of the basal ganglia with cross-correlation techniques. The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated. However, after dopamine depletion and induction of parkinsonism by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), oscillatory activity appeared and the firing of many neurons became correlated. We conclude that the normal dopaminergic system supports segregation of the functional subcircuits of the basal ganglia, and that a breakdown of this independent processing is a hallmark of Parkinson's disease.

Section snippets

Anatomical aspects of information processing in the basal ganglia

Information processing in neuronal systems is bound by the underlying anatomy. The basal ganglia are part of neural circuits that arise from the cortex, pass through areas of the basal ganglia and the thalamus and project back to the frontal cortex (Fig. 1). A comprehensive description of the cellular organization and anatomical connectivity of the basal ganglia has recently been published3, 4. Each of the structures in the basal ganglia–thalamo–cortical circuitry is composed of many (10⁴–10¹⁰)

Functional connectivity can be evaluated by cross-correlation methods

The study of cross-correlograms of the discharge activity of pairs of neurons that are recorded simultaneously24, 25 can reveal whether these neurons receive common inputs and whether they directly affect each other's activity. Common inputs lead to many coincident action potentials (Fig. 2C, left), resulting in a double-sided peak in the cross-correlation function (Fig. 2D, left). Flat cross-correlograms, on the other hand, indicate an absence of direct and indirect interactions between the

Firing of pallidal neurons is uncorrelated in the normal monkey

Cross-correlation studies in the pallidum of normal monkeys reveal that pallidal neurons fire independently[26]. Almost none of the cross-correlograms of pallidal cells of normal, awake, nonbehaving[28] and behaving monkeys[26] had significant double-sided peaks (Fig. 4A). Even when two neurons showed covariation of their discharge in response to behavioral events, the normalized spike-to-spike correlations (calculated by subtracting the expected rate covariation[25]) were also flat. The

The physiological basis of the motor symptoms of Parkinson's disease

Parkinson's disease is a very common disorder that affects the elderly and its symptoms are related to abnormal functioning of the basal ganglia33, 34. Besides problems with initiation and execution of movement (akinesia/bradykinesia), abnormal postural reflexes and muscular rigidity, a low-frequency tremor at rest is seen in many patients. These symptoms can be reproduced in primates treated with the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) dopaminergic neurotoxin. The biochemical,

Synchronous oscillations of basal ganglia neurons after MPTP treatment

Oscillatory activity has been described in several single-unit studies of the thalamus48, 49 and basal ganglia[50] of human parkinsonian patients. Periodic oscillatory activity of both low (4–7 Hz) and high (10–16 Hz) frequency was detected in the STN, GP and striatal TANs of MPTP-treated monkeys27, 28, 37, 38. The low-frequency oscillations were often correlated with the arm tremor. Our cross-correlation analysis of simultaneously recorded pallidal cells in MPTP-treated monkeys revealed that the

Concluding remarks

The independent firing of neurons in the output stage of the basal ganglia suggests that normal functioning of the basal ganglia is characterized by uncorrelated activity of their functional subcircuits (Fig. 5A, B). It is further postulated that dynamic reorganization of these functional subcircuits represents part of the neural substrate of innate motor learning52, 53. After the development of parkinsonian symptoms, the networks of the basal ganglia lose their ability to keep the activity of

Acknowledgements

This study was supported by grants from the Israel Academy of Science and the US–Israel Binational Scientific Foundation. We thank V. Zelanskaya for assistance with the histology, V. Sherkanski and M. Nakar for their continuous technical support, and T. Wichmann, E. Simon and O. Donchin for critical reading of this manuscript.

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Trends in Neurosciences

Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates

Abstract

Section snippets

Anatomical aspects of information processing in the basal ganglia

Functional connectivity can be evaluated by cross-correlation methods

Firing of pallidal neurons is uncorrelated in the normal monkey

The physiological basis of the motor symptoms of Parkinson's disease

Synchronous oscillations of basal ganglia neurons after MPTP treatment

Concluding remarks

Acknowledgements

Brain Res. Rev.

Brain Res.

Trends Neurosci.

Trends Neurosci.

Trends Neurosci.

Neuroscience

Brain Res.

Neuroscience

Brain Res.

Trends Neurosci.

Trends Neurosci.

Trends Neurosci.

Trends Neurosci.

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Brain Res.

J. Neurol. Sci.

Curr. Opin. Neurobiol.

Neurosci. Lett.

Lancet

Brain

The Basal Ganglia and their Relation to Disorders of Movement

Science

J. Neurophysiol.

Anatomy of the Cortex. Statistics and Geometry

J. Comp. Neurol.