Basal Ganglia George R. Leichnetz, Ph.D.

Transcription

1 Basal Ganglia George R. Leichnetz, Ph.D. OBJECTIVES 1. To understand the brain structures which constitute the basal ganglia, and their interconnections 2. To understand the consequences (clinical manifestations) of disease within specific nuclei I. DEFINITIONS The term basal ganglia applies to a functionally-related group of subcortical nuclei which belong to the extrapyramidal motor system and which influence movement without initiating it. This group of nuclei are involved in automated patterns of movement (e.g., walking, riding a bicycle, driving a car, choreography), "remembering" movements, and in that sense is related to "motor memory". Lesion of basal ganglia nuclei produces movement disorders (dyskinesias) collectively referred to as basal ganglia disease," and includes Parkinson's and Huntington's diseases. The basal ganglia affect motor function via loops (cortico-striato-pallido-thalamo-cortical) with the ipsilateral premotor cortex, particularly the supplementary motor area (M-II cortex) where movements are planned/programmed. These include the: Striatum: Caudate Nucleus Putamen Globus pallidus (Note: lenticular nucleus = globus pallidus + putamen) Subthalamic Nucleus Substantia Nigra From Burt, Textbook of Neuroanatomy

2 II. STRIATUM - Caudate and Putamen A. HISTOLOGY: histologically, the caudate and putamen are parts of the same structure, separated by the anterior limb of the internal capsule; they contain two populations of neurons: Spiny neurons - principal cell type; GABA-ergic; give rise to all striatal efferent projections (e.g., striatopallidals, striatonigrals) Aspiny neurons - intrinsic interneurons (short axons, do not leave striatum); cholinergic; involved in intrinsic striatal connections. B. PATCH-MATRIX ORGANIZATION: Striosomes or patches that have high density of muscarinic cholinergic (ACh) receptors, higher concentration of D1 receptors, and dense opiate binding; their striatal neurons project primarily to the globus pallidus, internal segment (GPi; direct pathway ) and substantia nigra, pars compacta (SNc). Matrix - striatal areas surrounding striosomes which have a higher concentration of D2 receptors, and dense calbindin and somatostatin binding; its neurons project primarily to the globus pallidus, external segment (GPe; indirect pathway ) and substantia nigra, pars reticulata (SNr); Note: Striatal efferents (striatopallidals and striatonigrals) originate from spiny neurons, which are GABA-ergic (inhibitory).

3 C. AFFERENT CONNECTIONS: 1. Corticostriates - from broad areas of cerebral cortex (glutamate, excitatory) Sensorimotor cortex to putamen; associational cortex to caudate 2. Thalamostriates - from intralaminar complex of thalamus (glutamate, excitatory); centromedian (CM) nucleus to putamen; parafascicular (Pf) nucleus to caudate nucleus 3. Nigrostriates - from substantia nigra, pars compacta (dopaminergic); not excitatory or inhibitory, probably neuromodulatory (via second messengers) From Haines, Fundamental Neuroscience

4 D. EFFERENT CONNECTIONS - (GABA-ergic) 1. Striatopallidals - to globus pallidus, external and internal segments; striosomes to GPi ( direct loop to thalamus) and matrix to GPe ( indirect loop, ie. side loop with subthalamic nucleus) Modified from: Kandel et al, Principles of Neural Science 2. Striatonigrals - striatum to substantia nigra, pars compacta (SNc) and reticulata (SNr) Striosomes to SNc and matrix to SNr E. CLINICAL SIGNIFICANCE: Huntington s Disease - an inherited disease with onset in middle age Atrophy of striatum results in a major loss of the principal spiny neurons of the striatum (GABA-ergic) and loss of intrinsic small (aspiny) cholinergic (ACh) neurons Lesion (or atrophy) results in Huntington s Disease with choreiform ( dance-like ) movement disorder (writhing movements, primarily involves distal limb muscles)

5 II. GLOBUS PALLIDUS The globus pallidus has two portions: external segment (GPe) and internal segment (GPi) The use of the term lentiform nucleus (putamen + globus pallidus) has been largely discontinued.

6 A. AFFERENT CONNECTIONS: 1. Striatopallidals (GABA) - from striatum (caudate and putamen) Striosomes to internal segment (GPi)- direct loop Matrix to external segment (GPe)- indirect loop 2. Subthalamo-pallidals (glutamate) - from subthalamic nucleus to GPi (feedback part of indirect loop ) From Haines, Fundamental Neuroscience B. EFFERENT CONNECTIONS: 1. Pallidothalamics - GABA - internal segment of the globus pallidus (GPi) produces a tonic inhibition of motor thalamic nuclei (VA); some pallidothalamics also terminate in the CM/Pf thalamic intralaminar nuclei (then feedback to straitum) Older names for pallidothalamic tracts: Fasciculus Lenticularis (H2) pallidothalamic fibers that cross thru internal capsule Ansa Lenticularis - pallidothalamics that loop around internal capsule Fasciculus lenticularis and ansa lenticularis join to form thalamic fasciculus (H1) to VA/VL nuclei of the thalamus 2. Pallidosubthalamic - (GABA)- GPe to subthalamic nucleus ( indirect loop )

7 C. CLINICAL SIGNIFICANCE: Since the principal outflow from the basal ganglia originates from the globus pallidus to the motor thalamus and cortex, it is often the target of neurosurgical interventions (pallidotomy or deep brain stimulation) to relieve tremors. III. SUBTHALAMIC NUCLEUS - Principal nucleus of subthalamus (ventral thalamus); its neurons are glutamatergic, excitatory (only excitatory neurons in the basal ganglia) The subthalamic nucleus is part of the subthalamus, ie. the part of the diencephalon ventral to the thalamus. Since it entertains connections with other parts of the basal ganglia and is associated with certain basal ganglia disease, it is included with this system. It is often the target of neurosurgical lesions to relieve basal ganglia-related tremors.

8 A. AFFERENT AND EFFERENT CONNECTIONS: Afferents - from globus pallidus, GPe (GABA)- indirect loop Efferents - to globus pallidus, GPi (glutamate)- indirect loop Indirect loop - increased subthalamic excitation of inhibitory pallidothalamics (in GPi) increases inhibition of the motor thalamus, reducing thalamocortical excitation of premotor cortex; decreased subthalamic excitation of GPi reduces inhibition of the motor thalamus and facilitates thalamocortical excitation of the premotor cortex (modified from Burt, Textbook of Neuroanatomy B. CLINICAL SIGNIFICANCE: Lesion: ballism (ballistic movements)- involves proximal limb and limb-girdle muscles, producing wild and flailing movements of the entire limb IV. SUBSTANTIA NIGRA A. SUBDIVISIONS: Pars compacta, SNc (DA) - heavily pigmented (neuromelanin, a by-product of catecholamine (DA) synthesis) Pars reticulata, SNr (GABA) - provides tonic inhibition to the motor thalamus (VA/VL) thalamic nuclei and superior colliculus (where a pause in activity allows eye movement to occur).

9 B. AFFERENT CONNECTIONS: 1. Striatonigrals - (GABA) -from striatum to pars reticulata (SNr) Striosomes - to SNc Matrix - to SNr C. EFFERENT CONNECTIONS: From Haines, Fundamental Neuroscience 1. Nigrostriates - (DA)- from pars compacta (SNc) to striatum 2. Nigrotectals - (GABA)- from pars reticulata (SNr) to superior colliculus 3. Nigrothalamics - (GABA)- from pars reticulata (SNr) to motor thalamus (VA/VL) and intralaminar thalamic nuclei

10 D. CLINICAL SIGNIFICANCE: From Haines, Fundamental Neuroscience Parkinson s disease- loss of DA neurons (loss of neuromelanin pigmentation) Resting tremor Bradykinesia- slowness, stiffness of movement Festinating gait (baby steps) "Freezing" - inertia, difficulty initiating movements Rigidity (shuffling gait) Expressionless face- (akinesia of facial muscles)

11 V. MOTOR CIRCUIT OF THE BASAL GANGLIA WITH THE CORTEX The internal segment of the globus pallidus and substantia nigra, pars reticulata provide tonic inhibition of motor thalamus and superior colliculus. Movements initiated in response to sensory, memory, or motivationally contingent cues are correlated with pauses in the tonic activity of inhibitory GPi or SNr output neurons. Outflow from basal ganglia (from globus pallidus) via motor thalamus affects premotor area 6 cortex (especially supplementary motor area) - and automated movements.

12 From Niewenhuys, The Human Nervous System If there is pathology in the basal ganglia, it affects the ipsilateral motor cortex, and clinical deficits (via the pyramidal tract) are expressed on the opposite side of the body. Deficits from lesions of the basal ganglia are expressed contralaterally. A Self-Assessment is available for this lecture. * Netter Presenter Image Copyright 2004 Icon Learning Systems. All rights reserved.