Basal Ganglia Dr. G.R. Leichnetz

Basal Ganglia The group of subcortical nuclei collectively known as the “basal ganglia” are involved in orchestrating automated patterns of movement, such as walking, driving a car, riding a bicycle. The term includes: caudate nucleus, putamen, globus pallidus, subthalamic nucleus, and substantia nigra.

The basal ganglia include: Caudate Putamen Globus pallidus Caudate nucleus The basal ganglia include: Caudate Putamen Globus pallidus Subthalamic nucleus Substantia nigra Striatum Subthalamic nucleus Putamen Globus pallidus Burt Substantia nigra

Striatum: caudate + putamen Lentiform nucleus: putamen + globus pallidus Caudate Nucleus Putamen Caudate Putamen Globus Pallidus Globus Pallidus

(which is involved in the planning and programming of movements). Supplementary Motor Cortex These structures have extensive interconnections, but ultimately their major output flows from the internal segment of the globus pallidus to the motor thalamus (VA/VL), and then is conveyed to the supplementary motor cortex (M-II) (which is involved in the planning and programming of movements). Motor thalamus Globus pallidus, GPi Subthalamic nucleus Striatum Substantia nigra From Kandel, et al.

Striatum

Striatum: Caudate and Putamen Caudate Nucleus Putamen Putamen GP Globus Pallidus In a Nissl-stained section the caudate and putamen are seen as histologically the same structure, separated by the anterior limb of the internal capsule.

The striatum consists of two populations of neurons: Spiny neurons are the principal cell type, are GABA-ergic, and give rise to all striatal efferents (striatopallidals & striatonigrals). Aspiny neurons are cholinergic, short-axon neurons which have intrinsic striatal circuitry (short axons which do not leave the striatum). From Parent, Carpenter’s Human Neuroanatomy

Striatum: Caudate and Putamen The striatum is organized into subsectors, the striosomes and matrix, that have differential connections. Caudate Nucleus Striosomes Matrix Putamen Haines, Fundamental Neuroscience D1 Dopaminergic receptors predominate in the striosomes; D2 receptors in the matrix From Parent, Carpenter’s Human Neuroanatomy

Corticostriates (glutamatergic, excitatory) Striatal Afferents Cortex There are three principal sources of afferents to the striatum (green): Corticostriates (glutamatergic, excitatory) Thalamostriates (glutamatergic, excitatory) Nigrostriates (dopaminergic) CM/Pf Intralaminar complex, thalamus Substantia nigra From Haines, Fundamental Neuroscience

Corticostriates Prefrontal Cortex Corticostriates originate from broad areas of frontal and parietal cortex. Those from association cortex (prefrontal & parietal) go to the caudate nucleus. Those from the sensorimotor cortex (pre- and post-central gyri) go to the putamen. Striatum

Thalamostriates originate from the centromedian (CM) and parafascicular (Pf) nuclei of the intralaminar complex of the thalamus. CM projects to the putamen. Pf projects to the caudate nucleus. Pulvinar Pineal Intralaminar Complex CM VPL Pf VPM Modified from Kandel

Nigrostriates Nigrostriate projections originate from the pars compacta of the substantia nigra. They are dopaminergic. SN Pars reticulata SNr Pars compacta SNc DA

Striatal Efferents The principal efferents of the striatum (red) are: Striatopallidals- “striosomes” to internal segment of the globus pallidus (GPi) & “matrix” to external segment (GPe) Striatonigrals “striosomes” to pars compacta (SNc) & “matrix” to pars reticulata (SNr) of substantia nigra All of the efferents of the caudate and putamen are GABA-ergic (inhibitory). From Haines, Fundamental Neuroscience

The direct pathway facilitates movement, while the indirect pathway inhibits movement. D1 receptors predominate in striosomes (patches) and project directly to the GPi (direct pathway). D2 receptors predominate in the matrix and project to the GPe (indirect pathway).

Huntington’s Chorea is an inherited disease with onset in middle age. Atrophy of the striatum Choreiform (dance-like) movements, rigidity (hyperkinetic movement disorder) Post-mortem coronal section of the brain of a patient with Huntington’s disease. Note atrophy of caudate and putamen and enlarged lateral ventricles.

Globus Pallidus

C Globus Pallidus The globus pallidus has two segments: external and internal P GP External segment (GPe) Internal segment (GPi) GP

Pallidal Afferents Striatopallidals The principal source of afferents to the globus pallidus is GABA-ergic striatopallidal fibers from caudate and putamen, which project to both external and internal segments. Striatopallidals to external segment affect the “indirect loop.” GPe GPi Striatopallidals to the internal segment affect the “direct” loop. Modified Burt, Textbook of Neuroanatomy

Pallidal Efferents: Pallidothalamics & Pallidosubthalamics All of the efferents of the globus pallidus are GABA-ergic (inhibitory). The external segment projects to the subthalamic nucleus (“indirect loop”; in green) and the internal segment projects directly (“direct loop”) to the motor thalamus (primarily VA) and to intralaminar complex (CM/Pf). VA Indirect Loop CM/Pf GPe STN GPi Modified Burt, Textbook of Neuroanatomy

Modified from Kandel The direct pathway facilitates movement, while the indirect pathway inhibits movement. D1 receptors predominate in striosomes (patches) and project directly to the GPi (direct pathway). D2 receptors predominate in the matrix and project to the GPe (indirect pathway).

Efferents of the globus pallidus primarily target the motor thalamus (pallidothalamics to VA). Some traverse the internal capsule (fasciculus lenticularis) and some loop around internal capsule (ansa lenticulus); join to form thalamic fasciculus. Pallidothalamics follow two different routes to the motor thalamus (VA) VA CM/Pf Thalamic fasciculus Fasciculus lenticularis STN Ansa lenticularis Pallidal Efferents

Subthalamic Nucleus

Subthalamic Nucleus The subthalamic nucleus is part of the subthalamus. Prerubral Fields H ZI H2 STN

Subthalamic Afferents The subthalamic nucleus receives its principal input from the external segment of the globus pallidus (GPe), and projects to the internal segment of the globus pallidus (GPi); the “indirect loop.” VA CM/Pf GPe STN

Modified from: Kandel Subthalamic nucleus

A lesion of the subthalamic nucleus results in contralateral hemiballism. Ballism- violent, large amplitude, proximal limb movements result from a lesion of the subthalamic nucleus. Huntington’s disease and hemiballism are hyperkinetic disorders (excessive motor activity)

Substantia Nigra

SN Substantia Nigra The substantia nigra has two parts: pars compacta (DA) and the pars reticulata (GABA). SN Pars reticulata Pars compacta

Substantia Nigra Afferents Substantia Nigra Afferents Striatonigrals: from caudate & putamen, GABA-ergic Striosomes- to pars compacta, SN (SNc) Matrix- to pars reticulata, SN (SNr) Caudate Putamen SNr SNc From Haines, Fundamental Neuroscience

Nigrostriatals (DA)- from SNc to caudate and putamen Nigral Efferents: Nigrostriatals (DA)- from SNc to caudate and putamen Nigrothalamics- from SNr to motor thalamus (VA/VL) (GABA-ergic) Nigrotectals- from SNr to superior colliculus (GABA-ergic) Modified from Haines, Fundamental Neuroscience

Substantia nigra: pars compacta (DA) to striatum, and pars reticulata (GABA)- to thalamus & superior colliculus VA & CM/Pf SC Striatum Nigrothalamics & nigrotectals GABA SNr SNc Nigrostriates DA

The nigrostriatal projection from the pars compacta of the SN to the caudate and putamen is dopaminergic. Loss of dopaminergic neurons in the SNpc is associated with Parkinson’s disease. L-dopa therapy is recommended to replace depleted DA (crosses blood brain barrier) Post-mortem section of the midbrain from a patient with Parkinson’s disease shows loss of neuromelanin in the SN

Parkinson’s Disease Resting tremor Bradykinesia Festinating Gait- baby steps “Freezing”(inertia)- difficulty initiating movements Rigidity Masked face Parkinson’s disease is a hypokinetic disorder (deficient motor activity)

Basal Ganglia Loop With Ipsilateral Cortex

The basal ganglia are in a neural loop with the ipsilateral motor cortex. Corticostriate projections originate from broad areas of the frontal and parietal cortex, but thalamocortical projections from VA, carrying the influence of basal ganglia, project more narrowly to the supplemental motor area (M2 premotor cortex) involved with the planning and programming of movements. From Kandel, et al.

Motor cortex Therefore, if lesioned, the dysfunction affects the ipsilateral motor cortex, and deficits (thru the pyramidal system) are expressed on the contralateral side of the body. The basal ganglia are connected in a loop with the ipsilateral motor cortex From: Niewenhuys, The Human Nervous System