Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Abstract

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goaldirected action.The basal ganglia are a group of subcortical nuclei that have been linked to movement control since the end of the nineteenth century when David Ferrier concluded that the corpus striatum contained "the centres of automatic or sub-voluntary integration" (REF. 1 Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts view was expanded in the early twentieth century by observations that basal ganglia lesions were associated with movement disorders (BOX 1). The first functional model of basal ganglia architecture was developed in the late 1980s (FIG. 1a). In this model, cortical inputs enter the basal ganglia through the striatum (in primates this consists of the caudate nucleus and the putamen), and the internal globus pallidus (GPi) and the substantia nigra pars reticulata (SNr) serve as the principal output nuclei. The activity of striatal medium spiny projection neurons is conveyed to the output nuclei (GPi and SNr) through a monosynaptic GABA (γ-aminobutyric acid)-ergic projection (the 'direct' pathway) and a polysynaptic ('indirect') pathway that involves relays in the external globus pallidus (GPe) and the subthalamic nucleus (STN) 2 , 3 . Output from GABAergic GPi and SNr neurons keep targeted structures in the thalamus and brainstem under tonic inhibitory control: this tonic inhibition is blocked (that is, paused) by phasic inhibitory signals from the 'direct' striato-nigralpallidal projection 4 , which releases thalamocortical and brainstem structures from inhibition, thereby allowing movement to proceed. Dopaminergic input from the substantia nigra pars compacta (SNc) modulates corticostriatal transmission by exerting a dual effect on striatal projection neurons (FIG. 1). Neurons that co-express dopamine D1 receptors, substance P and dynorphin and give rise to the 'direct pathway' are excited by dopamine, whereas neurons that co-express D2 receptors and encephalin, and that give rise to the 'indirect pathway', are inhibited 5 (FIG. 1a). Consequently, according to this model, in the normal state, activation of the 'indirect circuits' at the level of the striatum would promote movement inhibition or...

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