Abstract
According to the current model of the basal ganglia organization, simultaneous activation of the striato-nigral direct pathway by glutamatergic and dopaminergic neurotransmission should lead to a synergistic facilitatory action on locomotor activity, while in contrast activation of the indirect pathway by these two neurotransmittions should lead to antagonistic effects on locomotor activity. Based on published data, as a break with the current thinking, we propose a reconceptualization of functional interactions between dopaminergic and glutamatergic neurotransmission. In this model, dopaminergic neurotransmission is seen as a motor pacemaker responsible for the basal and primary activation of striatal output neurons and glutamate as a driver providing a multiple combination of tonic, phasic, facilitatory and inhibitory influxes resulting from the processing of environmental, emotional and mnesic stimuli. Thus, in the model, glutamate-coded inputs would allow tuning the intrinsic motor-activating properties of dopamine to adjust the production of locomotor activity into goal-oriented movements.
Highlights
The striatum including its dorsal and ventral parts, respectively the caudate-putamen and the nucleus accumbens, is the major input structure of the basal ganglia, which are a set of subcortical structures that is widely accepted to contribute to the control of motor activity and movements and to the processing of cognitive and ‘limbic’ functions
According to the anatomical organization of the basal ganglia from the striatum complex to the motor cortex, the model predicts that activation of either D1-like receptors or D2-like postsynaptic receptors leads to the production of locomotor activity as follows: activation by dopamine of the striato-nigral GABAergic output neurons is thought to provide a direct inhibitory action on the substantia nigra pars reticulata GABAergic neurons
If glutamate is considered as a neurotransmitter which activation can positively and negatively control both striatonigral and striato-pallidal output neurons, and in fine facilitate or inhibit the production of locomotor activity and movements mediated by D1-like receptor- or D2-like postsynaptic receptor activation, it could be predicted that the types of receptors and glutamatergic pathway activated would determine the direction in which functional interactions between glutamatergic and dopaminergic neurotransmission occur
Summary
The striatum including its dorsal and ventral parts, respectively the caudate-putamen and the nucleus accumbens, is the major input structure of the basal ganglia, which are a set of subcortical structures that is widely accepted to contribute to the control of motor activity and movements and to the processing of cognitive and ‘limbic’ (emotional and motivational) functions. According to the anatomical organization of the basal ganglia from the striatum complex to the motor cortex, the model predicts that activation of either D1-like receptors or D2-like postsynaptic receptors leads to the production of locomotor activity as follows: activation by dopamine of the striato-nigral GABAergic output neurons is thought to provide a direct inhibitory action on the substantia nigra pars reticulata GABAergic neurons.
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