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The basal ganglia is essential for voluntary movement. Critically discuss how the basal ganglia nuclei contribute to goal directed voluntary movement using clinical and experimental studies to support your argument.
To successfully execute a voluntary movement, involves the following steps, firstly the idea to move has to be developed, a series of motor commands within the central nervous system then have to be organised in order to carry out the movement, then activation of the correct muscles as well as continuous feedback to ensure that the movement is carried out smoothly. It is thought the basal ganglia contribute in providing some of the feedback within the central nervous system to ensure the smooth execution of movement (Stanfield, 2014). The basal ganglia are a set of associated subcortical nuclei; including the corpus striatum which itself includes both the caudate and the putamen; the globus pallidus which includes internal and external segments, the substantia nigra and the subthalamic nucleus (Nestler, Hyman & Malenka, 2009). The globus pallidus (internal) contains the output neurons of the basal ganglia, whereas the globus pallidus (external) contains cells that project to the subthalamamic nucleus, the subthalamic nucleus then projects back to the globus pallidus (internal). The connection between these nuclei of the basal ganglia is very complex, the corpus striatum is the main components that receive and process signals related to movement and the globus pallidus is the main source of output from the basal ganglia. The subthalamic nucleus and substania nigra pars compacta are less significant in movement but they do input to the corpus striatum and the pallidus. Most areas of the cerebral cortex extend directly to the striatum, making the cortex the primary source of input to the basal ganglia and output from the basal ganglia projects to the thalamus and from there back to the cortex (Purves, 2008). A motor circuit links the basal ganglia with the supplementary motor area and the premotor cortex and the primary motor cortex, and it is this link that allows the basal ganglia to contribute to goal directed voluntary movement (Samuel et al., 1997). This essay will address the mechanisms that the basal ganglia use to contribute to goal directed voluntary movement, and will critically evaluate aspects of these mechanisms.
The indirect and direct pathways have opposite effects on the projections of thalamic neurons. In the direct pathway, projections from cortical regions use the excitatory transmitter glutamate, and project to the striatum, thereby exciting medium spiny neurons within the striatum, in particular the putamen. Projections from the striatum to the globus pallidus (internal) and substantia nigra pars reticula use inhibitory transmitter GABA, the excitation of the striatum causes an increase in GABAergic projections thereby inhibiting activity in the globus pallidus (internal) and substantia nigra. The projections between the globus pallidus (internal) and the thalamus are again, inhibitory, because the GP (internal) and substantia nigra have been inhibited they cannot inhibit the action of the thalamus, this causes the thalamus to increase its firing and increase motor activity. The difference in the indirect pathway is that instead of the striatum projecting to the globus pallidus (internal) it instead projects to the globus pallidus (external), so instead inhibits the activity of the globus pallidus (external). This results in less inhibition of the subthalamic nucleus, which in turn, using glutamate causes excitation of the globus pallidus(internal). The increase in activity in the globus pallidus (internal) uses GABA to inhibit the activity of thalamic cells, thereby decreasing the firing of the thalamus resulting in a decrease in motor activity (Longstaff, 2000). It is thought that these processes result in the direct pathway initiating goal directed voluntary movement and the indirect pathway suppressing unwanted movement.
As well as receiving input from the cortex the striatum also receives input from the sustantia nigra pars compacta via dopaminergic projections which will either bind to D1 or D2 receptors on the medium spiny neurons of the striatum. Dopaminergic projections in the direct pathway are thought to use D1 receptors, and the projections in the indirect pathway are thought to use D2 receptors to reduce the transmission of the indirect pathway. Dopamine regulates basal ganglia circuitry, as they determine the output of the basal ganglia by either acting on D1 or D2 receptors, it is therefore assumed to be absolutely essential in the initiation of goal directed voluntary movement. The medium spiny neurons of the striatum signal to the substantia nigra pars reticula, the substantia nigra pars compact the sends dopaminergic projections back to the medium spiny neurons. D1 receptors are thought to facilitate voluntary movement by turning up the cortical input to the striatum, whereas D2 receptors decrease the input from the cortex to the striatum, thereby inhibiting voluntary movement (Squire, 2008).
However, although this is the principal model of how the basal ganglia contributes to the initiation of voluntary movement, a recent review conducted by Calabresi, Picconi, Tozzi, Ghiglieri and Di Filippo (2014) has suggested that the model simply describing two separate pathways that contribute to initiating voluntary movement may be too oversimplified. For example they looked at a study by Cazorla et al. (2014) who investigated the role of D2 receptors in basal ganglia circuitry. They looked at the basal ganglia in adult mice and found evidence that Globus Pallidus external collaterals may bridge the two pathways potentially meaning that the direct pathway can have an influence on the indirect pathway and vice versa, meaning that these two pathways may actually be more intertwined rather than separate. It also demonstrated that D2 receptors were heavily associated with these bridging collaterals Cui et al. (2013) developed an in vivo, neurophysiological technique to explore the indirect and direct pathways in spiny projection neurons. They used D1-Cre transgenic, direct pathway specific mice and A2A-Cre indirect pathway specific mice and looked at the expression of a genetically encoded calcium indicator, using fibre optics and time-correlated single-photon counting (TCSPC) to determine the activation of specific neurons. When the mice were completing operant tasks, it was found that the striatal neurons in the direct and indirect pathway were both co-activated during the initiation of movement and inactive when the mice were immobile. The current model suggests that there would be more activity in the direct pathway during movement than in no movement and more activity in the indirect pathway during immobility. Further investigation is needed; however, experiments like this do show that the exact workings of the indirect pathway, and direct pathways and how they help the basal ganglia contribute to goal directed voluntary movement may not work as previously thought.
Mink et al. (1996) suggest that the basal ganglia, through the pathways discussed, does not generate movement but when the cerebral cortex generates voluntary movement, the basal ganglia works to inhibit any other competing motor mechanisms that would cause interference with executing the desired voluntary movement. The pathways within the basal ganglia find the right balance to best allow for the execution of effective voluntary movement. This has been demonstrated recently in a study by Wan et al. (2011) used fMRI scans on amateur and professional board game players, they found activity in the caudate nucleus of the striatum of the professional board game players were needed for quick generation of the next appropriate movement in the board game. This study demonstrates not only the basal ganglia’s role for learning and memory but also the ability of the basal ganglia to inhibit competing mechanisms the could interfere with the smooth execution of goal directed voluntary movement.
Pallidotomy is a surgical lesion of the globus pallidus nucleus (Nestler, Hyman & Malenka, 2009) studies have demonstrated that this procedure can reduce motor problems seen in hypokinetic disorders such as Parkinson’s disease. Parkinson’s disease is characterised by the loss of dopaminergic projections in the substantia nigra, leading to an over activity in the globus pallidus (internal) which causes the motor disturbances seen in Parkinson’s such as bradykinesia (Dostrovsky, Hutchison & Lozano, 2002). Samuel et al. (1997) hypothesised that if pallidotomy was performed on the globus pallidus (internal) then joystick movement response times would improve and also there would be a local increase in cerebral blood flow to the thalamus, supplementary motor area and the prefrontal cortex. They performed pallidotomy on six people with Parkinson’s disease and performed PET scans pre and post operation while the subjects were instructed to move a joystick up, down, left or right. Task performance was measured on a computer and the regional cerebral blood flow measured using the PET scan. The clinical responses to pallidotomy included a 34.7% decrease in the Unified Parkinson’s Disease Rating Scale as well as an increase of 4.4% in activity of the supplementary motor area post-pallidotomy, increases in response times of joystick movements were also reported, although it should be noted that this was not significant. In conclusion they found that lesions of the globus pallidus reduces inhibition of the circuits between the thalamus and the cortex and increases activation of the supplementary motor area and prefrontal cortex, thereby alleviating some of the symptoms associated with Parkinson’s. This study and various other studies demonstrate the importance of the basal ganglia, in particular the globus pallidus (internal) and its direct effects on areas such as the supplementary motor area and the prefrontal cortex, areas that are critical in the execution of voluntary movement.
Huntington’s disease is another basal ganglia related disorder that results in
In conclusion it is evident that the basal ganglia plays a marked role in the initiation of voluntary movement. It is also evident that the indirect and direct pathways are key to this contribution as well as dopamine acting as a regulator to this pathway, however this essay has demonstrated that these set of nuclei are incredibly complicated and further research needs to be conducted to determine exactly how the indirect and direct pathways work together in controlling goal- directed voluntary movement as well as…Many experimental studies also use animal models of the basal ganglia, future research must be careful in generalising findings of the function of the basal ganglia in animals and applying them to humans.
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