Basal Ganglia and The Regulation of Movement

Abstract

The basal ganglia (BG) is composed of several heavily interconnected nuclei at the base of the cerebrum. A series of anatomically distinct parallel circuits through the BG receive afferent projections from and project back to cortical regions that mediate skeletomotor, oculomotor, frontal associative, and limbic functions. All circuits share a common intrinsic organization captured largely by the heuristic model of direct and indirect pathways that link BG input stations to outputs. Activation of the direct pathway may facilitate movement whereas the indirect pathway may suppress movement. Neuromodulators such as dopamine have different effects on activity and synaptic plasticity in the two pathways. Clinical disorders that involve the BG are often associated with movement disorders. Although the actual roles of the BG in the control of movement are still actively debated, growing evidence suggests it acts as a reinforcement‐driven tutor for learning automatic behavioural routines.

Key concepts

  • The BG is organized as anatomically segregated loop circuits that contribute to the control of movement, cognition and motivation.

  • All BG circuits share a common basic organization.

  • Input projections from cortex and thalamus terminate as excitatory synapses in the striatum and subthalamic nucleus.

  • Output projections tonically inhibit target neurons in thalamic and brainstem nuclei.

  • Direct and indirect pathways connect input and output nuclei of the BG.

  • Activation of the direct pathway facilitates movement whereas activation of the indirect pathway suppresses movement.

  • A variety of neuromodulators, such as dopamine, affect the activity of neurons in the direct and indirect pathways differently.

  • Most BG‐related clinical conditions (e.g. Parkinson disease) arise from imbalanced activation of direct and indirect pathways and involve abnormal discharge patterns in BG output neurons.

  • BG circuits may regulate how an animal allocates time and effort to movements and actions and act as a tutor for new skill learning.

Keywords: striatum; globus pallidus; dopamine; Parkinson disease; learning

Figure 1.

Circuit diagrams of the BG and associated input–output connections. (a) The positions of key BG structures involved in skeletomotor control and their basic input–output connectivity are indicated in a parasagittal section through the macaque brain. The basic loop circuit includes an excitatory glutamatergic (Glu) projection from the neocortex to the striatum (caudate nucleus and putamen) and then inhibitory (γ amino butyric acid‐containing; GABAergic) striatal projection (the ‘direct pathway’) to the internal globus pallidum (GPi). GABAergic neurons in GPi project to targets in the thalamus and brainstem. The main thalamic target of this basic circuit (VA/VL, ventral anterior/ventrolateral nucleus of the thalamus) projects to the frontal cortex including parts of the premotor and primary motor cortex. (b) The internal connectivity of the BG (dark background). Direct and indirect pathways start in striatal projection neurons that express D1‐ and D2‐type dopamine receptors, respectively. D2‐type neurons project to the external globus pallidum (GPe). GPe projects to the subthalamic nucleus (STN) and GPi. STN also receives monosynaptic Glu input from the motor cortices and projects to GPi and GPe. GPi sends GABAergic projections to VA/VL and the centre median–parafascicular intralaminar complex (CMPf) of the thalamus. CMPf closes another loop by projecting back to the striatum. GPi also projects to brainstem regions such as the pedunculopontine nucleus. Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc) innervate the striatum and, less densely, the GP and STN. (c) Anatomically segregated parallel circuits through the BG subserve skeletomotor, oculomotor, associative and limbic functions. All circuits obey a common internal organization. Distant yet functionally related regions of cortex send converging projections to a subregion of the striatum. Medium spiny neurons in each striatal subregion project to distinct subregions of the globus pallidus which in turn project to different regions of thalamus. (Only direct pathway structures are shown.) BG‐receiving subregions of thalamus project back to a subset of the cortical areas that project into each circuit. Descending projections from the GPi terminate in the pedunculopontine nucleus or superior colliculus (sup coll). The target of descending projections from the limbic circuit is not well established. Abbreviations: DL, dorsolateral; lat., lateral and med., medial.

Figure 2.

Abnormal discharge of neurons in GPi is a critical step in the network imbalances associated with Parkinson disease (b) and Huntington disease (c). In a normally functioning basal ganglia (a), balanced activation of direct and indirect pathways (starting in striatal D1 and D2 neurons, left) leads to intermediate GPi firing rates and random discharge patterns (right). (b) In Parkinson disease, the dopaminergic innervation of the striatum, pallidum and STN degenerates (dotted outline, left). The best‐understood consequence of this is increased activation of D2‐type indirect pathway neurons and decreased activation of D1‐type direct pathway neurons. The effects of dopamine denervation on pallidal and STN activity are less well understood. The cascading effects result in abnormal GPi activity marked by increased firing rates and rhythmic bursty firing patterns (right). (c) In early stage of Huntington'disease, D2‐type indirect pathway neurons degenerate selectively (dotted outline, left). The net effect on GPi activity is decreased firing rates and rhythmic bursty firing patterns (right). Diagrams on the left indicate the level of tonic activity in a pathway by the thickness of lines. Traces on the right show brief (approximately 2 s) epochs of action potential discharge (i.e. ‘spike trains’) recorded from three actual GPi neurons under each clinical condition. The spike train in (a) was recorded from the GPi of a normal macaque monkey. Single unit spike trains in (b) and (c) were recorded from human subjects undergoing surgery for deep brain stimulation. At the time scale used, individual action potentials appear as thin vertical lines of similar height above the level of background noise (thick horizontal bands).

Figure 3.

Disconnections of the BG skeletomotor circuit do not impair movement initiation or sequencing in a neurologically normal animal, but have a selective effect on movement speed and extent. (a) Single behavioural trials illustrate performance of a sequential movement task before and after an injection of muscimol (a long‐acting GABAergic inhibitory agent) into the GPi. Animals moved a joystick through a series of four out‐and‐back component movements (red, blue, green, and cyan traces, respectively). Targets were presented in fixed order. Spatial trajectories (left) and tangential velocities (right) of the joystick are plotted. Outward movements to capture a peripheral target often began before the instruction cue was presented (↓). GPi inactivation did not impair the smooth uninterrupted execution of the sequence even though movement extent and velocity were reduced (‘postinjection’). (b) Inactivations in the skeletomotor region of GPi had a negligible effect on reaction times (RTs; left, compare preinjection (open symbols) versus postinjection means (filled symbols)). This was true irrespective of whether animals performed over‐learned fixed sequences (‘Sequence’) or random sequences (‘Random’) or whether cues provided information by their spatial location (circles) or colour (triangles). In contrast, muscimol injections consistently reduced movement velocity (middle) and extent (right) under all conditions. Error bars±SEM.

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Further Reading

Bergman H and Deuschl G (2002) Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back. Movement Disorders 17: S28–S40.

Graybiel AM (2008) Habits, rituals, and the evaluative brain. Annual Review of Neuroscience 31: 359–387.

Nambu A (2004) A new dynamic model of the cortico‐basal ganglia loop. Progress in Brain Research 143: 461–466.

Redgrave P, Prescott TJ and Gurney K (1999) The basal ganglia: a vertebrate solution to the selection problem? Neuroscience 89: 1009–1023.

Schultz W (2007) Behavioral dopamine signals. Trends in Neuroscience 30: 203–210.

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Turner, Robert S(Sep 2009) Basal Ganglia and The Regulation of Movement. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000020.pub2]