Reading: Waxman pp. 141-146 are not very helpful! Computer Resources: HyperBrain, Chapter 12 Dental Neuroanatomy Suzanne S. Stensaas, Ph.D. April 22, 2010 THE BASAL GANGLIA Objectives: 1. What are the main manifestations of Basal Ganglia disease? 2. Be able to contrast signs and symptoms of: Basal Ganglia Disease Cerebellar Disease Corticospinal Tract Disease = Upper motor neuron Motor Neuron Disease = Lower Motor neuron 3. Identify the structures involved in: Huntington's Disease Parkinson's Disease I. Introduction A. General features of the basal ganglia, one of our 3 major motor control centers: 1. Involved in motor, cognitive and affective tasks 2. Do not project directly to targets below the midbrain 3. Act mainly on the premotor cortex via the thalamus, similar to cerebellum. B. What Do the Basal Ganglia Do? 1. We are beginning to understand that there are more than 3 different loops or parallel circuits and functions (motor, cognitive and affective) all influenced by a dopaminergic mesencephalic system. 2. The only one we will focus on is the motor loop. Motor pattern generators permit voluntary movements to take place in what seems like an automatic manor. 3. Normally the BG are the brakes on the voluntary motor system. 4. Selectively facilitate some movements and inhibit others, and/or compare commands for movement from the precentral motor cortex with proprioceptive feedback from the movement in progress. 5. Play a role in initiating internally generated movements C. Definitions 1. Basal ganglia a. Corpus striatum 1. Caudate \ = the striatum 2. Putamen / 3. Globus pallidus = the pallidum b. Though technically not part of the basal ganglia, the subthalamic nucleus and substantia nigra are presented with the basal ganglia because of their connections. 1
2. Lenticular nucleus is an old descriptive term for the lens-shaped gray matter just lateral to the internal capsule; it includes both the globus pallidus and putamen. Another term is lentiform, even more confusing. Avoid using either term. 2
From The Digital Anatomist Interactive Brain Syllabus. John Sundsten and Kate Mulligan, Univ. Washington School of Medicine. 1998 Source: Kandel? 3
II. Connections of Basal Ganglia A. The caudate and putamen are a single entity that is divided by the anterior limb of the internal capsule. Both have similar connections, cell types and neurotransmitters. There is evidence that the caudate is more involved in cognitive functions and the putamen more with motor functions B. Striatal Afferents 1. From the Cerebral CORTEX: Corticostriate afferents Nearly every region of the cerebral cortex sends axons to the ipsilateral caudate and putamen. (a. Visual cortex projects to the tail of the caudate and cells there respond to complex patterned visual stimuli.) b. Frontal cortex projects to the head of the caudate; therefore, this part of the caudate responds to environmental stimuli that are important in preparing for movement. 2. From the SUBSTANTIA NIGRA: Nigrostriatal afferents. These neurons use dopamine as their neurotransmitter C. Striatal Afferents and Efferents see diagram by Dr. Voron next page D. The Globus Pallidus Efferents to Thalamus 1. Pallidothalamic axons terminate in thalamic nuclei. In different region from the axons coming from the cerebellum. Myelin stained section through thalamus and BG, Stensaas 4
E. The Thalamic nuclei project to the premotor and supplementary cortex, area 6, in front of the precentral gyrus. F. The Cerebral Cortex Area 6 is the premotor and supplementary motor cortex. Region important in planning movements 1. Premotor cortex is the part of area 6 on the lateral surface of the hemisphere in front of the precentral gyrus.. Region important in planning movements 2. Supplementary motor cortex is the part of area 6 on the medial surface of the hemisphere.. Region important in planning movements 3. These areas then project to area 4 (the precentral gyrus), primary motor cortex and hence to the corticospinal tract. III. Striatal Motor Functions The striatum is thought to link sensory cues to motor behavior integrating nearly all the activity occurring in the cortex. 1. Many reciprocal connections (subthalamus and globus pallidus, substantia Stephen C. Voron, M.D., 2004 nigra and striatum). Excitatory (Glu): 2. A role in initiating internally generated movements like associated movement when walking. Cortex, Subth Nuc, VL Thal Inhibitory (GABA): 3. Interplay of inhibition and excitation results in normal motor behavior. Interruption of either the Direct or Indirect pathways results in decrease or increase in movement. We call these diseases: Movement disorders which usually occur at rest. Striatum, GPe, Gpi/(SNr) Both inhibitory and excitatory: SNc: dopamine Striatum interneurons: ACh Indirect pathway - Inhibits extraneous movement Direct pathway - Facilitates intentional movement 5
IV. Basal Ganglia Diseases-Often called Involuntary Movement Disorders. There may be an increase or a decrease in movements depending on the disease and structures involved. A. Involuntary movements during wakefulness. In general there are POSITIVE (hyperkinetic) signs such as rigidity, chorea, athetosis, resting tremor, etc. In addition there are NEGATIVE (hypokinetic) sympto ms such as akinesia, bradykinesia, masked face, decreased blinking, loss of associated movements, difficulty planning movements. B. Basal ganglia disease is relatively common and results from release (or disinhibition), Suzanne Stensaas C. Parkinson's disease was the first example of a neurological disorder with a molecular basis. It is a slowly progressive disorder characterized by bradykinesia (trouble initiating movement), festinating gait, resting tremor, lead pipe or cogwheel rigidity, and masked facies.. 1. Substantia nigra (pars compacta) contains pigmented dopaminergic neurons that project to the striatum; the dopamine has the general effect of facilitating movement. 2. In Parkinson's disease, >70% of dopaminergic neurons in the substantia nigra die. There is also neuronal loss in other monoaminecontaining nuclei, but the nigrostriatal dopamine loss is considered most important for the movement disorder. This loss in turn affects the direct pathway 3. L-DOPA therapy increases dopamine and provides significant improvement in movement in many patients. 6
D. Huntington's disease is an autosomal dominant disorder (CAG repeat) resulting in degeneration of cholinergic and inhibitory GABAergic neurons in the striatum and cerebral cortex, probably via glutamate-mediated excitotoxic mechanisms. Huntington's Disease usually includes choreoathetosis, dementia, and death within 10-20 years of the onset of symptoms. No specific treatment is available. Disease is often diagnosed after reproductive years reached and offspring produced. 7