1. Zhejiang University Ling Shucai 2011.12.12
Central Nervous System
The Basal Ganglia
Zhejiang University
Ling Shucai

2. Basal Ganglia What are the basal ganglia? Where are the basal ganglia?
Chemical Neuroanatomy of basal ganglia structures
Connections
Functions of the basal ganglia

3. What are the basal ganglia?
The basal ganglia (or basal nuclei) are a group of nuclei of varied origin (mostly telencephalic embryonal origin, with some diencephalic and mesencephalic elements) in the brains of vertebrates that act as a cohesive functional unit.

4. Coronal slices of human brain showing the basal ganglia
Coronal slices of human brain showing the basal ganglia. White matter is shown in dark gray, gray matter is show in light gray Anterior: striatum, globus pallidus (GPe and GPi) Posterior: subthalamic nucleus (STN), substantia nigra (SN)

6. VTA and reward learning
Ventral tegmental area (VTA). VTA efferents provide dopamine to the nucleus accumbens (ventral striatum) in the same way that the substantia nigra provides dopamine to the dorsal striatum. Because there is much evidence that it plays a central role in reward learning, the VTA→NA dopaminergic projection has attracted a great deal of attention.

7. VTA （ventral tegmental area）

8. What are the basal ganglia?
Anatomical subdivisions : Non-cortical nuclei in the forebrain
Dorsal Striatum: Caudate nucleus, Putamen
Ventral Striatum: Nucleus accumbens 伏核, Olfactory tubercle
Globus Pallidus: Internal and external segment, Ventral pallidum
Subthalamic nucleus 丘脑底核
Amygdala 杏仁核
Septal nuclei 隔核
Substantia nigra: Pars compacta, Pars reticulata
Pedunculopontine nucleus 脚桥核

9. Where are the basal ganglia?
They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas.

10. Head, body, tail of caudate
anterior and temporal horn of lateral ventricle
Globus pallidus internal and external
Internal capsule, anterior and posterior limbs

12. Caudate nucleus (body and tail)
Putamen and globus pallidus
Subthalamic nucleus
Substantia nigra:pars compacta and pars reticulata

13. Globus pallidus external
Globus pallidus internal
Subthalamic nucleus
Substantia nigra

14. Subthalamic nucleus, substantia nigra and sentral tegmental area

15. Rodent Brain

16. Chemical neuroanatomy of basal ganglia structures

17. Neurotransmitters
In most regions of the brain, the predominant classes of neurons use glutamate as neurotransmitter and have excitatory effects on their targets.
In the basal ganglia, however, the great majority of neurons use GABA as neurotransmitter and have inhibitory effects on their targets. The inputs from the cortex and thalamus to the striatum and STN are glutamatergic, but the outputs from the striatum, pallidum, and substantia nigra pars reticulata all use GABA. Thus, following the initial excitation of the striatum, the internal dynamics of the basal ganglia are dominated by inhibition and disinhibition.

18. Other neurotransmitters have important modulatory effects
Other neurotransmitters have important modulatory effects. The most intensively studied is：
Dopamine, which is used by the projection from the substantia nigra pars compacta to the striatum, and also in the analogous projection from the ventral tegmental area to the nucleus accumbens.
Acetylcholine also plays an important role, being used both by several external inputs to the striatum, and by a group of striatal interneurons. Although cholinergic cells make up only a small fraction of the total population, the striatum has one of the highest acetylcholine concentrations of any brain structure.

19. “Chemical Neuroanatomy” was very important in increasing our understanding of basal ganglia structures
From Zhou et al., Nature Neuroscience, 4, (2001) 

20. RST
RST

21. Basal Ganglia Disease
Parkinson's disease: loss of dopamine in the neostriatum
Treatment: increase dopamine
Schizophrenia: Too much dopamine
Treatment: Block some (D2) dopamine receptors.
Not enough DA
Parkinsons
Too much DA
Schizophrenia
‘Normal’

22. Diseases of the Basal Ganglia
Parkinson’s disease :
Akinesia 运动不能
Bradykinesia 运动弛缓
Resting tremor 静止性震颤
Rigidity 刻板
Huntington’s disease
Chorea 舞蹈病
Psychiatric disturbances
Dementia 痴呆

23. Connections

26. Connections Afferents (striatum):
Cerebral cortex (entire cortex)
Thalamus (intralaminar and midline nuclei)
Amygdala (basolateral nucleus)
Raphe nucleus, substantia nigra pars compacta, VTA（Ventral tegmental area ）
Efferents (Gpi, ventral pallidum, SNpr)
Ventral tier nuclei of thalamus 丘脑腹侧核层
Superior colliculus
Lateral habenular nucleus

28. All regions of cerebral cortex project to the basal ganglia, but output of basal ganglia is directed towards the frontal lobe, particularly pre-motor and supplementary motor cortex

29. Basic Circuit of Basal Ganglia
Cerebral Cortex
glutamate
GABA
Neostriatum + +
Gpi/SNpr
Gpe
Subth
GABA
glutamate
VA/VL thalamus
Connections of afferents and within basal ganglia are largely non-reciprocal

30. Basic Circuit of Basal Ganglia
Glutaminagic fibers
GABAergic fibers
Dopaminagic fibers

31. Direct vs indirect pathways
Different populations of spiny neurons
Enkephalin vs substance P
D1 vs D2 receptors
From Graybiel, A. Neural Networks, Am J Psychiatry 158:21, January 2001

32. Facilitation vs inhibition of movement
Akinetic disorders (运动不能）:
overactivity in the indirect pathway
Dopamine increases activity in the direct pathway and decreases activity in the indirect pathway
Loss of dopamine decreases activity in the direct pathway and increase activity in the indirect pathway
Hyperkinetic disorder （运动过度）:
overactivity in the direct pathway
Projections to the Gpe degenerate early in HD = removal of inhibition = increased activity of indirect pathway
Increased activity of indirect pathway = increased inhibition of subthalamic nucleus = decreased excitatory drive on direct pathway = decreased inhibition on thalamus

33. Summary of Forebrain Systems
Cortical vs subcortical
According to Swanson, the forebrain can be understood in terms of two systems:
Cortex and cortical (basal) nuclei
Cortical: glutamate projection neurons
Striatal: GABA projection neurons
Pallidal: GABA ---> Thalamus --> Cortex

34. Functions of the basal ganglia
The basal ganglia are associated with a variety of functions, including voluntary motor control, procedural learning relating to routine behaviors or "habits" such as bruxism, eye movements, and cognitive, emotional functions. Currently popular theories implicate the basal ganglia primarily in action selection, that is, the decision of which of several possible behaviors to execute at a given time.
Experimental studies show that the basal ganglia exert an inhibitory influence on a number of motor systems, and that a release of this inhibition permits a motor system to become active. The "behavior switching" that takes place within the basal ganglia is influenced by signals from many parts of the brain, including the prefrontal cortex, which plays a key role in executive functions.