Elsevier

Biosystems

Volume 59, Issue 1, January 2001, Pages 7-14
Biosystems

The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. II. Mechanism of synergistic modulation of thalamic activity via the direct and indirect pathways through the basal ganglia

https://doi.org/10.1016/S0303-2647(00)00135-0Get rights and content

Abstract

A possible mechanism underlying the modulatory role of dopamine, adenosine and acetylcholine in the modification of corticostriatal synapses, subsequent changes in signal transduction through the ‘direct’ and ‘indirect’ pathways in the basal ganglia and variations in thalamic and neocortical cell activity is proposed. According to this mechanism, simultaneous activation of dopamine D1/D2 receptors as well as inactivation of adenosine A1/A2A receptors or muscarinic M4/M1 receptors on striatonigral/striatopallidal inhibitory cells can promote the induction of long-term potentiation/depression in the efficacy of excitatory cortical inputs to these cells. Subsequently augmented inhibition of the activity of inhibitory neurons of the output nuclei of the basal ganglia through the ‘direct’ pathway together with reduced disinhibition of these nuclei through the ‘indirect’ pathway synergistically increase thalamic and neocortical cell firing. The proposed mechanism can underlie such well known effects as ‘excitatory’ and ‘inhibitory’ influence of dopamine on striatonigral and striatopallidal cells, respectively; the opposite action of dopamine and adenosine on these cells; antiparkinsonic effects of dopamine receptor agonists and adenosine or acetylcholine muscarinic receptor antagonists.

Introduction

The numerous movement disorders are explained by functional model of the cortico-basal ganglia-thalamocortical motor loop (DeLong, 1990). In humans, lesions at the basal ganglia levels lead to hypokinetic and hyperkinetic dysfunctions attributive to Parkinson's and Huntington's disease. Diverse changes in signal transduction through the basal ganglia can be caused by modifications in the efficacy of cortical inputs to the striatum, the entry structure of the basal ganglia. Plasticity of excitatory corticostriatal inputs, such as long-term potentiation and depression (LTP, LTD), involves convergent actions of glutamate, dopamine, adenosine and acetylcholine (Calabresi et al., 1992, Calabresi et al., 1998, Calabresi et al., 1999a). However, mechanism underlying different changes in signal transduction through the basal ganglia, produced by modulatory neurotransmitters, remains unclear. The aim of this work has been to analyze the feasible mechanisms of variations of neuronal activity in the cortico-basal ganglia-thalamocortical loop, triggered by modification of corticostriatal synapses. Earlier suggested modification rules (Silkis, 2001) were used for this analysis. According to these rules, an activation of dopamine D1 and D2, or adenosine A2A and A1, or muscarinic M1 and M4 receptors on striatal cells promotes the induction of LTP and LTD, respectively. Based on these rules we expected that modulatory neurotransmitters variously modify the neuronal interactions in the ‘direct’ and ‘indirect’ pathways through the basal ganglia, since different receptor types are expressed on striatal cells, originative these pathways.

Section snippets

Functional organization of the cortico-basal ganglia-thalamocortical ‘motor’ circuit

The main features and character of operation of the cortico-basal ganglia-thalamocortical ‘motor’ loop are widely described (Alexander and Crutcher, 1990, DeLong, 1990, Parent and Hazrati, 1995a, Parent and Hazrati, 1995b). Signals initiated in the precentral motor areas activate the inhibitory spiny cells in the putamen. This part of the striatum is one of the ‘input’ structures of the basal ganglia. Striatal cells inhibit ‘output’ neurons of the basal ganglia which are possess in the motor

Synergistic changes in the basal ganglia-thalamic transmission due to the opposite modification of cortical inputs to striatonigral and striatopallidal cells

According to earlier suggested modification rules (Silkis, 2001), an activation of dopamine D1 (D2) receptors leads to LTP (LTD) of excitatory cortical inputs to striatonigral (striatopallidal) cells and augmenting (lowering) GABA release into GPi/SNr (GPe). Actually, precisely this type of influence of D1, and D2 receptors on GABA release by striatonigral and striatopallidal cells has been obtained (Hossain and Weiner, 1995, Ferre et al., 1996a, Harsing and Zigmond, 1997, Hooper et al., 1997,

Correlation between effects emerging from proposed mechanism, and available data related to motor disorders and treatment of Parkinson's and Huntington's disease

The motor disorders at Parkinson's disease are thought to be a sequence of the deficit of dopamine, modification of cortical inputs to striatal cells and decrease of inhibition of output neurons of the basal ganglia (Gibb, 1997, Chase et al., 1998). Subsequent enlargement of the activity of output neurons causes inhibition of thalamic and cortical neurons and akinesia or rigidity. Huntington's disease is also associated with an activation of dopamine-sensitive receptors on striatal neurons and

Conclusion

According to the suggested modification rules for striatal synaptic plasticity, conjunctive activation (inactivation) of dopamine D1 receptors and inactivation (activation) of adenosine A1 or muscarinic M4 receptors on striatonigral neurons together with an activation (inactivation) of D2 receptors and inactivation (activation) of A2A or M1 receptors on striatopallidal neurons can promote LTP and LTD (LTD and LTP) of cortical inputs to striatonigral and striatopallidal cells, respectively.

Acknowledgements

This work was partly supported by Russian Foundation of Fundamental Research, grant 98-04-48368.

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