Relevant Anatomy and Physiology of Parkinson’s Disease
Substantia Nigra
The substantia nigra is located behind the cerebral peduncles in the central, lower area of the brain as part of the mesencephalon. High concentrations of neuromelanin are found in its cells giving it its relatively dark appearance and name. It has two parts the pars reticulata and the pars compacta. The pars compacta is the most relevant area of the brain in Parkinson’s Disease because it is the section that produces dopamine. The pars compacta contains approximately 28% of the dopamine producing neurons in the brain. The pars compacta synapses with the striatum through what is called the nigrostriatal pathway to deliver dopamine.
Striatum
The striatum is responsible for bringing together the dopamine signals from the substantia nigra with the voluntary movement signals from the prefrontal cortex. The striatum is composed of the caudate nucleus and the putamen which are separated by the internal capsule.
The striatum as part of the basal ganglia is involved in motor functions which is important in understanding the effects of PD. The two relevant pathways for the striatum are the direct and indirect pathways. The direct pathway is involved in voluntary muscle movement while the indirect pathway assists the voluntary movement by removing unnecessary muscle movements. These pathways arise from a signal starting in the prefrontal cortex that travels from the motor cortex first to the caudate nucleus of the striatum and then through a complicated set of structures resulting in either the desired movement or the inhibition of unwanted movement.
The striatum as part of the basal ganglia is involved in motor functions which is important in understanding the effects of PD. The two relevant pathways for the striatum are the direct and indirect pathways. The direct pathway is involved in voluntary muscle movement while the indirect pathway assists the voluntary movement by removing unnecessary muscle movements. These pathways arise from a signal starting in the prefrontal cortex that travels from the motor cortex first to the caudate nucleus of the striatum and then through a complicated set of structures resulting in either the desired movement or the inhibition of unwanted movement.
Bringing the Two Together
As mentioned before, the substantia nigra delivers dopamine to the striatum. The dopamine is delivered directly to the caudate nucleus. The caudate nucleus is also where the motor signals from the cortex are received. These signals come in the form of excitatory glutamate and act on the spiny projection neurons of the caudate. This interplay at the synapses of the striatum is the major relevance for dopamine and the substantia nigra in PD. The dopamine acts by modulating the corticostriatal synapses either through long-term potentiation(LTP) or long-term depression(LTD). LTP is the strengthening of neuron connections and LTD is the weakening of neuron connections. At the synapses dopamine targets “D1-like” ”D2-like” receptors. Although the mechanism is far from being understood a general rule is that the D1 receptors are responsible for LTP while the D2 receptors are responsible for LTD.
By modulating the corticostriatal synapses with dopamine motor learning can occur. If a favorable action is taken and higher amounts of dopamine are released then that motor pathway will be up-regulated and it will be easier in the future for that action to be done again because the brain has "learned" that action produces reward. It is important to note that the substantia nigra can not initiate any movement, proven through deep-brain stimulation, even though its degradation in PD whic causes impairment of motor function might suggest that.
By modulating the corticostriatal synapses with dopamine motor learning can occur. If a favorable action is taken and higher amounts of dopamine are released then that motor pathway will be up-regulated and it will be easier in the future for that action to be done again because the brain has "learned" that action produces reward. It is important to note that the substantia nigra can not initiate any movement, proven through deep-brain stimulation, even though its degradation in PD whic causes impairment of motor function might suggest that.
Sources
Bear, M. F., Connors, B.W. & Paradiso M. A., Neuroscience: Exploring the Brain, Second Edition, 351 West Camden St., Baltimore, MD: Lippincott Williams & Wilkins, 2001, pp 473-482
Calabresi, P., Picconi, B., Tozzi, A., and Di Filippo, M. (2007). Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends in Neurosciences 30, 211–219.
Wickens, J.R., Reynolds, J.N., and Hyland, B.I. (2003). Neural mechanisms of reward-related motor learning. Current Opinion in Neurobiology 13, 685–690.
http://www.neuroanatomy.wisc.edu/virtualbrain/BrainStem/20Substantia.html
Calabresi, P., Picconi, B., Tozzi, A., and Di Filippo, M. (2007). Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends in Neurosciences 30, 211–219.
Wickens, J.R., Reynolds, J.N., and Hyland, B.I. (2003). Neural mechanisms of reward-related motor learning. Current Opinion in Neurobiology 13, 685–690.
http://www.neuroanatomy.wisc.edu/virtualbrain/BrainStem/20Substantia.html