Basal Ganglia

Function of the substantial nigra pars compacta

substantia nigra pars compact releases dopamine. Dopamine binds to D2 receptors and has an inhibitory effect on the indirect pathway. Dopamine binds to D1 receptions and has an excitatory effect on the direct pathway. As a result, both unwanted and wanted movements are promoted: by activating the direct pathway and by inhibiting the indirect pathway. This is required to actually activate the direct pathway, without it, the excitatory input from other sources is not enough to activate that pathway.

Neurotransmitters involved:

Dopamine: can be excitatory or inhibitory. Acts as an inhibitory neurotransmitter on the indirect pathway. Acts as an excitatory neurotransmitter on the direct pathway. GABA: inhibitory, important in direct and indirect pathway. Glutamate: excitatory, involves AMPA and NMDA receptors, this makes the excitatory effect more controllable compared to other excitatory neurotransmitters. Input from cortex into putamen and caudate. Important in the indirect pathway.

Hemiballism

characterized by wild flinging movements of the body and results from lesion in the subthalmic nucleus. The excitatory glutamate input to the globus pallidus internal from the subthalmic nucleus is lost from the lesions. This results in less inhibition of the thalamus which leads more (over) excitation of neurons in the motor cortex. This finally results in uncontrollable hyperactivity of the motor system and muscles. Unwanted movements are no longer actively inhibited.

Huntington's chorea

Can cause hyperkinesia characterized by spontaneous, rapid, involuntary, and purposeless jerks in variable locations on the body, uncontrollable by the patient. It's a result of loss of GABAeric cells in the striatum that project only to the globus pallidus external. This means the thalamus can't be inhibited so there is uncontrollable hyperactivity of the motor system and muscles. There is no longer active inhibition of unwanted movements.

Parts of the Basal Ganglia

Gray matter structures deep in the telencephalon (some also found in the diencephalon/midbrain). The structures which make up the Basal Ganglia include the corpus striatum, which is made of the putamens and the Caudate nuclei, the sub thalamic nucleus, and the substantial nigra pars compact, the substantial nigra pars reticulate, the globes pallid us external segment, and the globus pallidus internal segment. Major components that receive and process movement related signals: -Corpus striatum (caudate and putamen) -Pallidum (globus pallidus internal and external segment, and the substantial nigra pars reticulata) -globus pallidus internal segment influences limb movement via increasing or decreasing inhibition on thalamus -Substantia nigra pars reticulata influences eye movements via superior colliculus -globus pallid us external segment is part of the indirect pathway and sends info to globes pallidus internal segment and sub thalamic nucleus. Smaller structures: substantial nigra pars compacta (provides dopaminergic input into caudate and putamen). Subthalamic nucleus (provide input into globus pallidus internal segment.

Baseline activities and response properties

Medium spiny neurons (MSN) in the putamen and caudate. Medium spiny neurons are receiving input from: cortical neurons (glutamate, excitatory input). Dopaminergic cells of substania nigra, and local circuit neurons (excitatory to inhibitory input). Response of MSN (input from the cerebral cortex) can be modulated by dopamine. Medium spiny neurons are silent at rest and require large amounts of inputs to become active due to inward rectifying potassium channels which close in response to depolarization. Medium spiny neurons are GABAergic, their primary output goes to globus pallidus and stubstantia nigra pars reticulata and is inhibitory. Globus pallidus (internal and external segment): neurons are tonic active at rest. Output neurons are GABAnergic, meaning their output is inhibitory. Sub thalamic nucleus: output neurons excrete glutamate, they are excitatory.

Dyskinesia

Side effect of taking I-dopa as a treatment for Parkinson's disease. It increases the overall availability of dopamine within the brain. This issue is that it not only helps to intitiate the direct pathway (which is the intended effect of the drug) but because it elevates the level of dopamine globally, it can also effect the indirect pathway, and if that does out of balance, it amplifies unwanted movements, leading to uncontrolled unwanted movements of the body similar to Huntington's and Hemiballism because the inhibitory effect of dopamine on the indirect pathway shuts down this pathway.

Basal ganglia

System of structures that influences motor neurons. This system acts to carry out wanted movement, and suppresses unwanted movement. It makes use of a range of neurotransmitters to act as excitatory or inhibitory. A direct pathway exists to release inhibitn on the thalamus to initiate wanted movements, and an indirect pathway exists to increase inhibition on the thalamus to inhibit movements that would interfere.

Direct and Indirect pathways

The basal ganglia has the center surround organization because the combination of indirect pathways that results in promoting certain movements (center) while suppressing everything else that would interfere (surrounding). The organization is one where the indirect pathways are on the outside, surrounding the direct pathways, acting as an effective filter for the direct pathway. Direct pathway: control of certain wanted movements in basal ganglia by means of striatum. Striatum = caudate and putamen. Caudate= eye movements. Putamen= limb and trunk movement. Pathway: Cerebral cortex uses glutamate to excite the striatum (caudate and putamen) uses GABA to inhibit Globus pallidus INTERNAL and substantia nigra pars reticulata, globus pallidus internal uses GABA to inhibit the VA/VL complex of thalamus, while substantial nigra pars reticulata uses GABA to inhibit the superior colliculus AND VA/VL complex of thalamus, VA/VL complex of thalamus sends information to motor cortex to initiate the movement. Direct pathway in action: cerebral cortex excites striatum, so striatum sets off an inhibitory chain (inhibits the inhibition of the thalamus with other words releases its inhibition) to initiate movement. Step by step: inhibition of globus pallidus increases, which shuts down its inhibitory effect on the thalamus (releasing the inhibition on the thalamus), and thus increases the excitatory effects of the thalamus on the cortex. Indirect pathway: The indirect pathway controls unwanted movements through increasing the inhibition on the thalamus. It's assumed the indirect and direct pathways create a proper balance of movements. The indirect pathway is used to inhibit neurons that are not needed for the task. Pathway: cerebral cortex uses glutamate to excite the striatum (caudate and putamen) uses GABA to inhibit globus pallidus EXTERNA, globus pallidus external uses GABA to a) inhibit the globus pallidus internal, and b) inhibits the sub thalamic nucleus which uses glutamate to have excitatory effects on the globus pallidus internal > globus pallidus internal uses GABA to inhibit VA/VL complex of thalamus which sends information to motor cortex. Indirect pathway in action: globus pallidus external is inhibited which releases inhibition on globus pallidus internal and the sub thalamic nucleus. Both leads to the increase in activity within the globus pallidus internal, which in tern increases the inhibition on the thalamus (strengthening the inhibition of unwanted movements).

What happens when there are certain deficits in the pathways? Parkinson's disease:

symptoms: all symptoms ( except for tremor) are directly related to a lack of dopaminergic input to the direct pathway and thus a decrease or inability in initiating wanted/appropriate movements. -diminished facial expressions, lack of associated movements due to difficulties with the initiation of wanted/appropriate movements. -difficulty initiating movement -slowness of movement (bradykinesia) -tremors of hands, arms, legs, jaw, etc. (not directly related to the discussed circuit alone). -stiffness of trunk -impaired balance and coordination Biological reasons behind the disease: -loss of dopaminergic neurons within the substantial nigra pars compacta. -aggregation of protein alpha-synuclein (lewy bodies)