Describe development of Basal ganglia
The first neurons generated in the cerebral periventricular zone migrate short distances. They aggregate as subcortical islands of gray matter (basal ganglia or basal nuclei) in the cerebral white matter.
Caudate and Putamen together are called_______
Globus Pallidus and Putamen together are called______
Structures taht modulate motor cortex with Basal ganglia
1. Striatum: Caudate, putamen, ventral striatum 2. Globus pallidus: External (lateral) part (GPe), internal (medial) part (GPi) 3. Subthalamic nucleus 4. Substantia Nigra: Pars reticulata (SNr) and pars compacta (SNc)
How do basal ganglia modulate the motor activity of the frontal cortices?
• Basal ganglia receive inputs from cerebral cortex • Basal ganglia modulate thalamus • Thalamus regulates motor cortex • Through the thalamus, basal ganglia participate in the initiation and control of voluntary movement
The substantia nigra projects to the ______ to release _______
What is the effect of the dopamine released by substantia nigra on striatum?
Dopamine regulates basal gangliar function, thus indirectly regulating cortical control of movement
What is the effect of basilar output onto thalamus
- Basal gangliar output inhibits the thalamus, thereby suppressing an excitatory thalamocortical projection. - The degree of thalamic inhibition therefore dictates modulation of cortex-dependent motor activity. - Because lesions affecting the basal ganglia disturb basal gangliar output and hence cortical activity, movement often suffers.
Corticostriatal fibers release ________ to excite striatal neurons
What region of the Substantia nigra a) releases neurotransmitter on to striatal cells, b)What neurotransmitter is released , c) what is the effect of the neurotransmitter and d) on which receptor does the neurotransmitter bind?
a) Pars compacta (SNc) b) Dopamine c) excitatory or inhibitory d) D1 (excitatory), D2 (inhibitory)
The substantia nigra receives inhibitory ______ signals from the striatum
GABAergic output from the MEDIAL (internal) part of the globus pallidus (GPi) inhibits cells _________________
GABAergic output from the medial (internal) part of the globus pallidus (GPi) inhibits cells of the ventral anterior and ventral lateral thalamic nuclei
Thalamic cells excite the motor cortex via the release of _______
What is the effect of striatum on globus pallidus internal?
– Suppresses activity in the GPi – Decreased output from the GPi increases thalamic activity – Increased thalamic activity increases cortical activity to facilitate movement
What is the effect of Globus Pallidus on Thalamus?
-secretes GABA to suppress thalamic output
Describe Direct Basal Gangliar Motor Loop
What is the effect of Subthalamic nucleus on Globus Pallidus medial?
Releases Glutamate to activate GPi and increase GABA release and thereby suppression of thalamus
Describe the Indirect Basal Gangliar Motor Loop
Effect of Direct circuit on movement
o Striatal output suppresses activity in the GPi
o Decreased output from the GPi increases thalamic activity
o Increased thalamic activity increases cortical activity to facilitate movement
Effect of INDirect circuit on movement
o Striatal output suppresses activity in the GPe
o Decreased output from the GPe increases output from the Sth
o Increased output from the Sth increases activity within the GPi
o Increased activity within the GPi inhibits the thalamus o Decreased thalamic output decreases cortical activity, thereby diminishing movement
Role of Striatal Dopamine in movement
Tonically released dopamine arising from the substantia nigra optimizes the output of the two basal gangliar circuits to normalize movement
Normal Role of Basal Ganglia in Voluntary Movement
- Normal initiation and maintenance of voluntary motor activity depends on basal gangliar output
- Normal basal gangliar activity regulates motor cortices to optimize communications between upper and lower motor neurons
- Optimized communication between upper and lower motor neurons depends on delicately balanced activities of direct and indirect basal gangliar components
o Unbalanced influences of the direct and indirect pathways on the GPi (and hence the thalamus) yield either hypo- or hyperkinesis
What defect causes Hypokinesis in Parkinson's disease?
pathologically diminished release of striatal dopamine secondary to degeneration of the dopaminergic nigrostriatal tract
– The net effect is increased inhibition of the thalamus, leading to decreased cortical activity and hypokinesis
Effect of Diminished dopamine on the Direct pathway
o Diminished activation of excitatory D1 receptors reduces striatal output within the direct basal gangliar pathway
o Diminished striatal output disinhibits the GPi
o The overly active GPi suppresses the thalamus
o Decreased thalamic activity decreases cortical output, suppressing movement
Effect of Diminished dopamine on the INDirect pathway
o Decreased stimulation of inhibitory striatal D2 receptors disinhibits striatal cells contributing to the indirect pathway
o Increased activity of striatal cells inhibits cells in the GPe
o Decreased activity in the GPe disinhibits the Sth
o Increased excitatory output from the Sth increases activity within the GPi
o Increased activity within the GPi suppresses thalamic activity
o Decreased thalamic activity reduces cortical excitation
o Reduced cortical activity once again diminishes voluntary movement
What causes drug induced Parkinsonism?
– Antipsychotic drugs like Phenothiazines, (DA receptor blockers)
– Depletors of DA stores (e.g., reserpine)
– Toxic contaminants (MPTP)
What produces MPTP?
a contaminant produced during improper preparation of a synthetic narcotic
How does MPTP induce Parkinsonism?
by damaging nigral mitochondria
What receptors do phenothiazines block ?
How do phenothiazines cause drug induced Parkinsonism?
by limiting dopamine-mediated inhibition of striatal neurons of the indirect pathway