The Basal Ganglia

What are the basal ganglia?• Dorsal Striatum

– Caudate nucleus– Putamen

• Ventral Striatum– Nucleus Accumbens– Olfactory Tubercle

• Globus Pallidus– Internal segment– External segment– Ventral pallidum

• Subthalamic nucleus• Substantia nigra

– Pars compacta– Pars reticulata

• Pedunculopontine nucleus**

Other Terms:

Archistriatum

Paleostriatum

Neostriatum

Where are the basal ganglia?

•Caudate Nucleus

•C shaped structure (“tail”)

•Lateral wall of lateral ventricle

•Head, body and tail

•claustrum•Septum pellucidum•Insular cortex•Corpus callosum

•Caudate nucleus•Putamen•Nucleus accumbens•Internal capsule•External capsule•Extreme capsule

•Caudate nucleus•Putamen•Globus pallidus external•Globus pallidus internal•Ventral pallidum

•Anterior commissure•Substantia innominata•Internal capsule•Lentiform nucleus**

•Head, body, tail of caudate

• anterior and temporal horn of lateral ventricle

•Globus pallidus internal and external

•Internal capsule, anterior and posterior limbs

•Caudate nucleus (body and tail)•Putamen•Globus pallidus•Subthalamic nucleus•Substantia nigra

•Pars compacta•Pars reticulata

•Subthalamic nucleus

•Substantia nigra

•Globus pallidus external

•Globus pallidus internal

•Subthalamic nucleus

•Substantia nigra

•Ventral tegmental area

Rodent Brain

Globus pallidus and entopeduncular nucleus

vs.

Globus pallidus (external) and Globus pallidus (internal)

“Chemical Neuroanatomy” was very important in increasing our understanding of basal ganglia structures

From Zhou et al., Nature Neuroscience, 4, 1224 - 1229 (2001) 

•Use of different histochemical and immunocytochemical stains revealed more extensive striatal structures than previously thought

•Also caused revised views of basal ganglia structures in non-mammals and pointed to considerable homologies between birds, mammals and reptiles

Functions of the basal ganglia• Extrapyramidal motor system• Motor planning, sequencing and learning• Activity of striatal neurons is not sufficiently explained by the

stimuli presented or the movements performed, but depends on certain behavioral situations, certain conditions or particularly types of trials

• -sensory stimuli but only when the elicit movements• -instruction cues (go-no go)• -memory related cues• -reward (especially ventral striatum)• -self-initiated moves

• Basal ganglia distinguished from cerebellum by connections with limbic system

Diseases of the Basal Ganglia

Huntington’s disease•Chorea

•Psychiatric disturbances

•Dementia

Parkinson’s:

•Akinesia

•Bradykinesia

•Resting tremor

•Rigidity

Cytoarchitecture

• Main neurotransmitter in basal ganglia is GABA

• 95% of neurons in neostriatum are medium spiny neurons (rodent)– Contain GABA– Principal neurons: project to

globus pallidus and SNpr– Subpopulations are distinguished

by peptides, neurotransmitter receptors and connections

– Receive bulk of afferent input• Several populations of interneurons

– aspiny– ACh, GABA/parvalbumin,

GABA/calretinin; GABA/NPY/NADPH/Somatostatin

From Groves, Brain Res. 286: 109, 1983

The Neostriatal Mosaic• Neostriatum divided

into two compartments: patch (striosome) and matrix

• First described by Ann Graybiel in 1978 using AChE stain

• Not visible in Nissl stains (“hidden chemoarchitecture”)

• Define input/output architecture of neostriatum

From Holt et al., 1997, JCN

Connections

• Afferents (striatum):– Cerebral cortex (entire cortex)– Thalamus (intralaminar and midline nuclei)– Amygdala (basolateral nucleus)– Raphe, substantia nigra pars compacta, VTA

• Efferents (Gpi, VP, SNpr)– Ventral tier nuclei of thalamus– Superior colliculus

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

Basic Circuit of Basal Ganglia

Neostriatum

Gpi/SNpr

Cerebral Cortex

VA/VL thalamus

+

+

Gpe

Subth

+

Disinhibition

From Chevalier and Deniau, TINS 13:277, 1990

Direct vs indirect

pathways

From Graybiel, A. Neural Networks, Am J Psychiatry 158:21, January 2001

•Different populations of spiny neurons

•Enkephalin vs substance P

•D1 vs D2 receptors

Functional subdivisions

• Sensorimotor– Putamen + globus pallidus/SNpr– SNpc

• Association– Caudate nucleus + globus

pallidus/SNpr– SNpc

• Limbic– Nucleus accumbens +

ventral pallidum– VTA From Parent, TINS 13: 254, 1990

Parallel Circuits

Alexander GE, DeLong MR, Strick PL., Annu Rev Neurosci. 1986;9:357-81

Neostriatal Mosaic and Input/Output Organization

• Most inputs to the neostriatum terminate in a patchy fashion (“matrisomes”)

• Input from a given cortical region terminates over an extended anterior-posterior extent

• Functionally related cortical areas project to the same patches

• Output neurons to a given efferent subregion are also arranged in patches

• Neurons in patches project to both Gpi/SNpr and GPe

From Graybiel et al., The basal ganglia and adaptive motor control, Science, 265: 1826, 1994

Cortex

Neostriatum

Gpi/SNpr

“divergent-reconvergent processing”

Direct and Indirect Pathways

Facilitation vs inhibition of movement

Akinetic disorders: 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

•Increased activity in the indirect pathway = increased activity in the direct pathway = increased inhibition on thalamus

Hyperkinetic disorder: 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

Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders.Trends Neurosci. 1989 Oct;12(10):366-75.

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